Study Evaluating CMC-544 In B-Cell Non-Hodgkin's Lymphoma

A Phase 1 Study Of Cmc-544 Administered As A Single Agent In Subjects With B-cell Non- Hodgkin's Lymphoma

To determine the Maximum Tolerated Dose (MTD), the tolerability, and the initial safety profile of CMC-544 in subjects with B-cell Non-Hodgkin's Lymphoma (NHL).

Study Overview

• Status: Completed
• Conditions: Lymphoma, B-Cell
• Intervention / Treatment: Drug: Inotuzumab ozogamicin [CMC-544]

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Gasthuisberg
• France
  • Paris, France, 75010
    • Hopital Saint Louis
  • Pierre Benite Cedex, France, 69495
    • Centre Hospitalier Lyon-Sud
• Germany
  • Mainz, Germany, 55131
    • Universitaetsmedizin der Johannes Gutenberg-Universitaet
  • Muenchen, Germany, 81377
    • Medizinische Klinik und Poliklinik III, Klinikum der Universitat Muenchen-Grosshadern
  • Muenchen, Germany, 81377
    • Universitaet Muenchen Klinikum Grosshadern
  • NRW
    • Bonn, NRW, Germany, 53105
      • Universitätsklinikum Bonn
• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
• Switzerland
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew'S Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35233
      • UAB CCC Clinical Studies Unit
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Kirklin Clinic
    • Birmingham, Alabama, United States, 35294
      • UAB Russell Ambulatory Pharmacy
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Faculty Foundation
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who have been previously diagnosed with CD22-positive, B-cell NHL, according to WHO classification, which has progressed after at least 2 prior therapies of probable clinical benefit
• At the expanded cohort, part 2 of the study, subjects must have one of the following:
• Follicular lymphoma previously treated with at least one dose of rituximab, but have not received radioimmunotherapy
• Diffuse large B-cell lymphoma
• Age 18 years or older

Exclusion Criteria:

• Candidate for potentially curative therapies in the opinion of the investigator
• Chronic lymphocytic leukemia
• Burkitt's lymphoma, primary effusion lymphoma, and precursor B-cell lymphoblastic lymphoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inotuzumab ozogamicin; Inotuzumab ozogamicin, iv, dose escalation and expanded cohort at 1.8mg/m2	Drug: Inotuzumab ozogamicin [CMC-544]; CMC-544, IV, dose escalation trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events (TEAE) are defined as any new event reported after first dose of study drug up to 42 days after last dose of study drug, or any event that is worse in severity than at any time during the baseline period. AEs included both SAEs and non-serious adverse events (non-SAEs).	Baseline up to 42 days after last dose of study drug (up to Day 225)
Number of Participants With Grade 3 or Higher Grades Treatment-Emergent Adverse Events (TEAEs) Based on Severity	AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE severity was defined to be the maximum toxicity grade of the treatment-emergent adverse events (TEAEs) experienced by the participants during the study. AE was assessed according to severity; Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening or disabling AE), Grade 5 (death related to AE). Participants with Grade 3 or higher grades TEAEs were reported.	Baseline up to 42 days after last dose of study drug (up to Day 225)
Maximum Tolerated Dose (MTD): Part 1 (Dose Escalation Cohorts)	MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced dose limiting toxicity (DLT). DLT was defined as any of the following events occurring during the first 21 days (or 28 days for participants treated every 4 weeks) days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 non-hematologic toxicity except grade 3 alopecia, nausea, or vomiting, any grade 4 febrile neutropenia, any grade 4 thrombocytopenia or any bleeding episode requiring platelet transfusion, any grade 4 absolute neutrophil count (for a duration of greater than or equal to [>=] 7 days), delayed recovery (less than or equal to [<=] grade 1 or baseline) from a toxicity that delays the initiation of the next dose by more than 2 weeks.	Baseline up to Day 28
Number of Participants With Dose-limiting Toxicity (DLT)	DLT was classified as per National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) version 3.0 and defined as any of the following events occurring during the first 21 days (or 28 days for participants treated every 4 weeks) days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 non-hematologic toxicity except grade 3 alopecia, nausea, or vomiting, any grade 4 febrile neutropenia, any grade 4 thrombocytopenia or any bleeding episode requiring platelet transfusion, any grade 4 absolute neutrophil count (for a duration of greater than or equal to [>=] 7 days), delayed recovery (less than or equal to [<=] grade 1 or baseline) from a toxicity that delays the initiation of the next dose by more than 14 days.	Baseline up to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS): Evaluable Population- Part 2 (Lead-in + Expanded Cohorts)	PFS was based on Kaplan-Meier estimates. PFS was defined as the time interval from the first dose of study medication until the first date on which relapsed disease, or progression (as per the International Response Criteria for Non-Hodgkin Lymphoma) or death, was documented, censored at the last tumor evaluation date. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma.	Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)
Progression-Free Survival (PFS): Intent-to-treat Population-Part 2 (Lead-in + Expanded Cohorts)	PFS was based on Kaplan-Meier estimates. PFS was defined as the time interval from the first dose of study medication until the first date on which relapsed disease, or progression (as per International Response Criteria for Non-Hodgkin Lymphoma) or death, was documented, censored at the last tumor evaluation date. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma.	Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)
Overall Survival (OS): Evaluable Population- Part 2 (Lead-in + Expanded Cohorts)	OS was based on Kaplan-Meier method. Survival was defined as the time period from the first dose of study drug until the date of death, censored at the participant's last contact date. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma.	Baseline up to Year 5
Overall Survival (OS): Intent-to-treat Population: Part 2 (Lead-in + Expanded Cohorts)	Interval OS was based on Kaplan-Meier method. Survival was defined as the time period from the first dose of study drug until the date of death, censored at the participant's last contact date. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma.	Baseline up to Year 5
Number of Participants With Best Overall Response (BOR): Part 2 (Expanded Cohorts)	Participants with BOR=with complete response(CR),unconfirmed CR(CRu) or partial response (PR) as per International Response Criteria for NHL. CR: Total disappearance of all detectable clinical,radiographic sign of disease/related symptoms,normalization biochemical abnormalities related to NHL;if enlarged before therapy all lymph nodes,nodal masses,other organs regressed to normal size and spleen regressed in size,undetectable on physical exam,clear bone marrow infiltrate. CRu: CR but allows for residual lymph node mass >1.5 cm in greatest transverse diameter and all individual nodes previously merged were regressed by >75% in product diameters and indeterminate bone marrow. PR:>=50% decrease in sum of products of greatest diameters(SPD) of 6 largest dominant nodes/nodal masses,no increase in size of other nodes/spleen/liver, 50% decrease in SPD of splenic,hepatic nodules,involvement of other organs considered assessable,not measurable disease with exception of splenic,hepatic nodules.	Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)
Duration of Overall Response (DoR): Part 2 (Lead-in + Expanded Cohorts)	Duration of overall response was defined as the time from the date that measurement criteria were met for CR, CRu, or PR (whichever status was recorded first) until the first date that relapsed disease was objectively documented as per International Response Criteria for NHL, taking as reference for relapsed disease the smallest measurements recorded since the treatment started. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma.	Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)
Time-to-Tumor Progression: Part 2 (Expanded Cohorts)	Time to tumor progression was defined as the interval from the start of the treatment until the first date on which relapsed disease or progression is documented, censored at the last disease assessment. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma.	Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response- Evaluable Population: Part 2 (Lead-in + Expanded Cohorts)	Participants (having follicular or diffuse lymphoma) with objective response based assessment of CR, CRu or PR as per International Response Criteria for NHL. CR: Total disappearance of all detectable clinical, radiographic sign of disease/related symptoms, normalization biochemical abnormalities related to NHL; if enlarged before therapy all lymph nodes, nodal masses, other organs regressed to normal size and spleen regressed in size, undetectable on physical exam, clear bone marrow infiltrate. CRu: CR but allows for residual lymph node mass >1.5 cm in greatest transverse diameter and all individual nodes previously merged were regressed by >75% in product diameters and indeterminate bone marrow. PR: >=50% decrease in SPD of 6 largest dominant nodes or nodal masses, no increase in size of other nodes, spleen or liver, 50% decrease in SPD of splenic, hepatic nodules, involvement of other organs considered assessable, not measurable disease with exception of splenic, hepatic nodules.	Baseline up to 42 days after last dose (Day 225)
Percentage of Participants With Objective Response- Intent-to-treat Population: Part 2 (Lead in+ Expanded Cohorts)	Participants (having follicular or diffuse lymphoma) with objective response based assessment of CR, CRu or PR as per International Response Criteria for NHL. CR: Total disappearance of all detectable clinical, radiographic sign of disease/related symptoms, normalization biochemical abnormalities related to NHL; if enlarged before therapy all lymph nodes, nodal masses, other organs regressed to normal size and spleen regressed in size, undetectable on physical exam, clear bone marrow infiltrate. CRu: CR but allows for residual lymph node mass >1.5 cm in greatest transverse diameter and all individual nodes previously merged were regressed by >75% in product diameters and indeterminate bone marrow. PR: >=50% decrease in SPD of 6 largest dominant nodes or nodal masses, no increase in size of other nodes, spleen or liver, 50% decrease in SPD of splenic, hepatic nodules, involvement of other organs considered assessable, not measurable disease with exception of splenic, hepatic nodules.	Baseline up to 42 days after last dose of study drug (Day 225)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2003
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: December 4, 2003
• First Submitted That Met QC Criteria: December 4, 2003
• First Posted (Estimate): December 5, 2003

Study Record Updates

• Last Update Posted (Actual): December 17, 2018
• Last Update Submitted That Met QC Criteria: December 14, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Lymphoma; B-Cell; Non-Hodgkin's
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Inotuzumab Ozogamicin
• Other Study ID Numbers: 3129K1-100; B1931002 (Other Identifier: Alias Study Number)