Denna sida har översatts automatiskt och översättningens korrekthet kan inte garanteras. Vänligen se engelsk version för en källtext.

Study Evaluating Inotuzumab Ozogamicin [CMC-544] Administered In Combination With Rituximab In Subjects With Non-Hodgkin's Lymphoma (NHL)

6 februari 2018 uppdaterad av: Pfizer

A Phase 1/2 Study Of Cmc-544 Administered In Combination With Rituximab In Subjects With Follicular Or Diffuse Large B-cell Non-hodgkin's Lymphoma

The purpose of the study is to determine the tolerability, the initial safety profile and maximum tolerated dose, and to obtain preliminary information on the antitumor activity of inotuzumab ozogamicin [CMC-544] in combination with rituximab in subjects with follicular, diffuse large B-Cell, or mantle cell NHL.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Studietyp

Interventionell

Inskrivning (Faktisk)

119

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Australien
    • Brisbane, QLD
      • Herston, Brisbane, QLD, Australien, 4029
        • Royal Brisbane and Women'S Hospital
  • Belgien
      • Gent, Belgien, 9000
        • Universitair Ziekenhuis Gent
      • Gent, Belgien, 9000
        • University Hospital Gent - Department of Hematology
    • Vlaams-brabant
      • Leuven, Vlaams-brabant, Belgien, 3000
        • Universitair Ziekenhuis Leuven - Campus Gasthuisberg
  • Frankrike
      • Le Chesnay, Frankrike, 78157
        • Hôpital André Mignot
      • Paris, Frankrike, 75010
        • Hôpital Saint-Louis
      • Pierre Benite, Frankrike, 69495
        • CH Lyon sud
  • Förenta staterna
    • Alabama
      • Birmingham, Alabama, Förenta staterna, 35249 - 3300
        • University of Alabama at Birmingham-
      • Birmingham, Alabama, Förenta staterna, 35249
        • IDS Pharmacy
      • Birmingham, Alabama, Förenta staterna, 35294
        • University of Alabama at Birmingham-
    • California
      • Greenbrae, California, Förenta staterna, 94904
        • California Cancer Care, Inc.
      • San Francisco, California, Förenta staterna, 94143
        • University of California Medical Center
      • San Mateo, California, Förenta staterna, 94402
        • California Cancer Care
    • Georgia
      • Atlanta, Georgia, Förenta staterna, 30322
        • Emory University Hospital
      • Atlanta, Georgia, Förenta staterna, 30322
        • Emory Clinic
      • Atlanta, Georgia, Förenta staterna, 30322
        • Emory University Investigational Drug Service
    • Illinois
      • Chicago, Illinois, Förenta staterna, 60611
        • Northwestern Medical Faculty Foundation
    • Nevada
      • Las Vegas, Nevada, Förenta staterna, 89135
        • Nevada Cancer Institute-
    • New York
      • Buffalo, New York, Förenta staterna, 14263
        • Rosewell Park Cancer Institute
    • Ohio
      • Canton, Ohio, Förenta staterna, 44718
        • Gabrail Cancer Center
      • Cleveland, Ohio, Förenta staterna, 44195
        • Cleveland Clinic
      • Cleveland, Ohio, Förenta staterna, 44106
        • University Hospitals of Cleveland
      • Dover, Ohio, Förenta staterna, 44622
        • Gabrail Cancer Center
      • Westlake, Ohio, Förenta staterna, 44145
        • UHHS - Westlake
    • Pennsylvania
      • Philadelphia, Pennsylvania, Förenta staterna, 19111
        • Fox Chase Cancer Center
    • Texas
      • Houston, Texas, Förenta staterna, 77030-4009
        • The University of Texas M.D. Anderson Cancer Center
  • Hong Kong
      • Shatin N.T., Hong Kong
        • Prince of Wales Hospital
  • Italien
      • Roma, Italien, 00161
        • Universita La Sapienza Cattedra di Ematologia
  • Korea, Republiken av
      • Seoul, Korea, Republiken av, 138-736
        • Asan Medical Center
  • Nederländerna
    • Zuid-holland
      • Rotterdam, Zuid-holland, Nederländerna, 3015 CE
        • Erasmus Medisch Centrum--
  • Polen
      • Warszawa, Polen, 02-781
        • Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie
  • Schweiz
      • Zurich, Schweiz, 8091
        • University Hospital Zürich
  • Spanien
      • Barcelona, Spanien, 08028
        • Hospital Clinic i Provincial de Barcelona
  • Storbritannien
      • London, Storbritannien, EC1M 6BQ
        • Bart's Cancer Institute; Queen Mary University of London
    • Devon
      • Plymouth, Devon, Storbritannien, PL6 8DH
        • Derriford Hospital - Plymouth
    • Hampshire
      • Southampton, Hampshire, Storbritannien, SO16 6YD
        • Somers Cancer Science Building MP824
  • Tyskland
      • Bonn, Tyskland, 53105
        • Universitaetsklinik Bonn, Medizinische Klinik und Poliklinik III
      • Mainz, Tyskland, 55131
        • Universitaetsmedizin der Johannes Gutenberg-Universitaet, III. medizinische klinik und Poliklinik

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  • Subjects with CD20 and CD22-positive, follicular or diffuse large B-cell NHL who have not responded or progressed after 1 or 2 prior therapies; or subjects with CD20 and CD22-positive intermediate/aggressive NHL (diffuse large B-cell, mantle cell, transformed follicular or follicular grade 3b NHL) who have not responded or progressed after 1 or more prior therapies and are refractory to a previous rituximab containing therapy.
  • Prior therapy must contain at least one course of rituximab therapy, as single agent or in combination.
  • Measurable disease.

Exclusion Criteria:

  • Subjects who are candidates for other potentially curative therapies.
  • Subjects must not have received previous radioimmunotherapy.
  • Subjects who have undergone a prior bone marrow transplantation within the last 6 months.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Icke-randomiserad
  • Interventionsmodell: Faktoriell uppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB (FOLLICULAR)
Follicular
Läkemedel: inotuzumab ozogamicin
IV, 1.8 mg/m2, q4w
Andra namn:
  • CMC-544
Läkemedel: Rituximab
rituximab 375 mg/m^2 via IV infusion on Day 1
Experimentell: INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB (DLBCL)
Diffuse Large B-cell Lymphoma
Läkemedel: inotuzumab ozogamicin
IV, 1.8 mg/m2, q4w
Andra namn:
  • CMC-544
Läkemedel: Rituximab
rituximab 375 mg/m^2 via IV infusion on Day 1
Experimentell: INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB (REFRACTORY)
Refractory Aggressive NHL
Läkemedel: inotuzumab ozogamicin
IV, 1.8 mg/m2, q4w
Andra namn:
  • CMC-544
Läkemedel: Rituximab
rituximab 375 mg/m^2 via IV infusion on Day 1

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamicin in Combination With Rituximab (375 mg/m^2 )
Tidsram: First 28-day cycle
Inotuzumab ozogamicin was dose escalated (3 to 6 evaluable participants enrolled per dose cohort) during the first 28 days after the first administration of inotuzumab ozogamicin + rituximab. Enrollment at the next dose level or enrollment of additional subjects into a cohort proceeded according to the following criteria: 0 dose-limiting toxicity (DLT) by Day 28 of first dose move to higher dose, 1 participant reporting DLT but no others in cohort by Day 28 of first dose move to higher dose, greater than 2 participants reporting DLT by Day 28 of first dose stop and prior dose level considered MTD. The worldwide medical monitor and investigators reviewed all significant study drug-related toxicities to determine if the dose escalation rules were satisfied and whether the dose escalation schedule required modification.
First 28-day cycle
Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population)
Tidsram: Protocol reporting period of from informed consent to at least 28 days after the last dose. This outcome measure time frame: From the first dose of study drug to up to 56 days after the last dose of either study drug.
A TEAE is any event that occurred after the first dose of study drug up to 56 days post the last dose of study drug (either rituximab or inotuzumab ozogamicin).
Protocol reporting period of from informed consent to at least 28 days after the last dose. This outcome measure time frame: From the first dose of study drug to up to 56 days after the last dose of either study drug.

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Percentage of Participants With Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR)
Tidsram: Approximately every 2 (during treatment) or 3 (during follow-up) to 6 months for up to 5 years from 1st dose
CR: a. Complete disappearance of all detectable clinical and radiographic evidence of disease, disease-related symptoms, and normalization of NHL assignable biochemical abnormalities ; b. lymph nodes and nodal masses must have regressed to normal size; c. Spleen regressed in size and not palpable on physical exam, size of other organs enlarged due to disease decreased in size; d. Repeat bone marrow infiltrate clear. CRu: CR but allows for a. Residual lymph node mass >1.5 cm in greatest transverse diameter has regressed by more than 75% in diameter. Individual nodes that were previously confluent regressed more than 75 % in their product diameters; b. Indeterminate bone marrow. PR: a. ≥50 % decrease in product of the diameters (SPD) of the 6 largest dominant nodes or nodal masses; b. No increase in size of other nodes, liver, or spleen, c. Liver or spleen nodules regressed ≥50% in the SPD; d. Other organs usually assessable, no measurable disease present.
Approximately every 2 (during treatment) or 3 (during follow-up) to 6 months for up to 5 years from 1st dose
Kaplan-Meier Estimates of Progression Free Survival (PFS)
Tidsram: From the date of first dose of test article until the first date on which disease progression or death was documented or new anticancer start, any of which could be reported up to 5 years post last dose
The Kaplan-Meier method was used to determine PFS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by >= 50% in the size of previously involved sites, c. >= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. >= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver.
From the date of first dose of test article until the first date on which disease progression or death was documented or new anticancer start, any of which could be reported up to 5 years post last dose
Kaplan-Meier Estimates of the Probability of Being Progression Free at 6 Months
Tidsram: From the first dose to 6 months after first dose
Progression Free Survival is defined as the time interval from the first dose of test article until the first date on which relapsed disease, progression, initiation of new anti-cancer treatment due to persistent/refractory disease, or death was documented, censored at the last tumor evaluation.
From the first dose to 6 months after first dose
Kaplan-Meier Estimates of Overall Survival (OS)
Tidsram: From the first dose up to 5 years post last dose
OS was defined as the time from randomization to death due to any cause, censoring at the date of last contact. The Kaplan-Meier method was used to determine OS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
From the first dose up to 5 years post last dose
Kaplan-Meier Estimates of the Probability of Survival at 6 Months
Tidsram: From the first dose to 6 months after first dose.
Overall Survival (OS) was defined as the time from randomization to death due to any cause, censoring at the date of last contact. The Kaplan-Meier method was used to determine OS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
From the first dose to 6 months after first dose.
Kaplan-Meier Estimates of Time to Tumor Progression (TTP)
Tidsram: From the date of first dose of test article until the first date on which disease progression or death was documented, any of which could be reported up to 5 years post last dose.
TTP is defined as the interval from the first dose of the test article until the first date on which relapsed disease or progression, or death secondary to progression is documented, censored at the last disease assessment. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by >= 50% in the size of previously involved sites, c. >= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. >= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver. The Kaplan-Meier method was used to determine TTP. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
From the date of first dose of test article until the first date on which disease progression or death was documented, any of which could be reported up to 5 years post last dose.
Kaplan-Meier Estimates of the Probability of Being Event Free at 6 Months
Tidsram: From enrollment to up to 6 months from 1st dose.
Time-to-Tumor Progression (TTP): is defined as the interval from the first dose of the test article until the first date on which relapsed disease or progression, or death secondary to progression is documented, censored at the last disease assessment. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by >=50% in the size of previously involved sites, c. >= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. >= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver. The Kaplan-Meier method was used to determineTTP. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
From enrollment to up to 6 months from 1st dose.
Duration of Response (CR+CRu+PR)
Tidsram: Time from date measurement criteria are met for CR, CRu, or PR (whichever status is recorded first) until the first date relapsed disease or date of death (whichever occurs first) is objectively documented.
Time from date measurement criteria met for CR, CRu, or PR (whichever occurred first) until first date relapsed disease/date of death. CR: Complete disappearance of all detectable clinical, radiographic evidence of disease, disease-related symptoms, normalization of NHL assignable biochemical abnormalities; lymph nodes, nodal masses regressed to normal size; spleen size regressed, not palpable on physical exam, size of other organs enlarged due to disease. CRu: CR but allows for: residual lymph node mass >1.5 cm in greatest transverse diameter that regressed >75% in product diameter. Individual nodes previously confluent, regressed by >75% in their product diameters; Indeterminate bone marrow. PR: ≥50% decrease in SPD of 6 largest dominant nodes/nodal masses; No increase in size of other nodes, liver, or spleen; Splenic/hepatic nodules regressed by ≥50% in SPD; Except splenic/hepatic nodules, involvement of other organs assessable and no measurable disease present.
Time from date measurement criteria are met for CR, CRu, or PR (whichever status is recorded first) until the first date relapsed disease or date of death (whichever occurs first) is objectively documented.
Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Serum concentration of inotuzumab ozogamicin on Dosing Days 30 and 58 were measured. AUCinf of inotuzumab ozogamicin was reported. AUCinf: AUClast (area under the serum concentration-time profile for inotuzumab ozogamicin from time zero to the time of the last quantifiable concentration) +(Clast [last quantifiable concentration]/kel [elimination rate constant]) where Clast is the predicted serum concentration of inotuzumab ozogamicin at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
AUClast of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Serum concentration of inotuzumab ozogamicin on Dosing Days 1, 30 and 58 were measured. AUC of inotuzumab ozogamicin was reported. AUClast is area under the serum concentration-time profile from time zero to the time of the Clast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Time of the Last Quantifiable Serum Concentration in a Dosing Interval (Tlast) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Tlast of inotuzumab ozogamicin on Dosing Days 1, 30, and 58 was reported. Tlast: Time of last quantifiable concentration of inotuzumab ozogamicin. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Steady-state serum concentrations of inotuzumab ozogamicin on Dosing Days 1, 30 and 58 were measured. AUCtau of inotuzumab ozogamicin was reported. AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Peak Serum Concentration (Cmax) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Serum concentration of inotuzumab ozogamicin on Dosing Days 1, 30, and 58 were measured. Cmax of inotuzumab ozogamicin was reported. Cmax was observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Time to Reach Maximum Concentration (Tmax) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Average Serum Concentration at Steady State (Cav) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Cav: AUCtau (Area under the concentration time profile)/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Cmin: Lowest concentration observed during the dosing interval tau. Observed directly from data from Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Clearance (CL) of Serum Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Clearance is defined as Dose/AUCinf. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Steady-state Volume of Distribution (Vss) of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab MTD+Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Vss of inotuzumab ozogamicin on Dosing Days 30 and 58 were reported. Vss=CL*MRT (mean residence time). Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
MRT of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
MRT: AUMCinf/AUCinf - DOF (degrees of freedom)/2, where AUMCinf is the area under the first moment curve derived using the linear/log trapezoidal method, and DOF is the duration of the IV infusion dose. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
AUCinf of Total Calicheamicin (Conjugated + Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
AUCinf: AUClast+(Clast/kel) where Clast is the predicted serum concentration at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
AUClast of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Area Under the Steady-state Serum Concentration-time Curve (AUCtau) for Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Peak Serum Concentration (Cmax) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Time of Observed Maximum Concentration (Tmax) of Total Calicheamicin (Conjugated+Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence.

Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Average Serum Concentration (Cav) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Cav: AUCtau/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Minimum Observed Serum Trough Concentration (Cmin) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Cmin: Lowest concentration observed during the dosing interval tau. Observed directly from data from Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Clearance (CL) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Clearance defined as Dose/AUCinf. Corresponds to Dosing Day 30 for Cycle 2 and dosing Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Steady-state Volume (Vss) of Total Calicheamicin (Conjugated Plus Unconjugated) Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Vss: Steady-state volume of distribution CL*MRT of inotuzumab ozogamicin Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Mean Residence Time (MRT) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
MRT: AUMCinf/AUCinf - DOF/2, where AUMCinf is the area under the first moment curve derived using the linear/log trapezoidal method, and DOF is the duration of the IV infusion dose. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Serum Decay Half-Life (t1/2) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Area Under the Steady-state Serum Concentration-time Curve (AUClast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Peak Serum Concentration (Cmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Time of Observed Maximum Concentration (Tmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin + Rituximab on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Minimum Observed Serum Trough Concentration (Cmin) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin+Rituximab on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Cmin: Lowest concentration observed during the dosing interval tau. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
AUCinf: AUClast+(Clast/kel) where Clast is the predicted serum concentration at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Area Under the Steady-state Concentration-time Curve (AUClast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD+ Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Peak Concentration (Cmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Time to Reach Maximum Concentration (Tmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tidsram: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Average Serum Concentration (Cav) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Cav: AUCtau/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Cmin: Lowest concentration observed during the dosing interval tau. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Clearance (CL) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Clearance defined as Dose/AUCinf. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Steady-state Volume (Vss) of Inotuzumab Ozogamicin Antibody Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Tidsram: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Vss: Steady-state volume of distribution CL*MRT of inotuzumab ozogamicin Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Pfizer

Samarbetspartners

UCB Pharma

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Användbara länkar

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

4 maj 2006

Primärt slutförande (Faktisk)

19 maj 2014

Avslutad studie (Faktisk)

2 juni 2014

Studieregistreringsdatum

Först inskickad

2 mars 2006

Först inskickad som uppfyllde QC-kriterierna

2 mars 2006

Första postat (Uppskatta)

6 mars 2006

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

8 mars 2018

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

6 februari 2018

Senast verifierad

1 februari 2018

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • 3129K3-101
  • B1931004 (Annan identifierare: Alias Study Number)
  • 2005-005436-27 (EudraCT-nummer)

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

Kliniska prövningar på B-cells lymfom

Kliniska prövningar på inotuzumab ozogamicin

Sök liknande försök

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

CROs by country

CROs in El Salvador

Betingelser

Sällsynta sjukdomar

Läkemedelsinterventioner

Kosttillskott

Sponsor / medarbetare

Platser

3
Prenumerera