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A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab

4 mars 2020 mis à jour par: Pfizer

A PHASE 1 STUDY OF PF-05082566 AS A SINGLE AGENT IN PATIENTS WITH ADVANCED CANCER, AND IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH NON-HODGKIN'S LYMPHOMA (NHL)

A study of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb), in patients with solid tumors or b-cell lymphomas, and in combination with rituximab in patients with CD20 positive Non-Hodgkin's Lymphoma (NHL).

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

190

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Australie
    • Victoria
      • Melbourne, Victoria, Australie, 3000
        • Peter MacCallum Cancer Centre
  • France
      • RENNES cedex 9, France, 35033
        • Centre d'investigation Clinique
  • Italie
    • BO
      • Bologna, BO, Italie, 40138
        • Az. Ospedaliera-Univer. di Bologna Policlinico S. Orsola Malpighi
    • MI
      • Milano, MI, Italie, 20132
        • Ospedale San Raffaele di Milano
  • Japon
      • Akita, Japon, 010-8543
        • Akita University Hospital
      • Tokyo, Japon, 135-8550
        • The Cancer Institute Hospital of Japanese Foundation For Cancer Research
    • Chiba
      • Kashiwa, Chiba, Japon, 277-8577
        • National Cancer Center Hospital East
  • États-Unis
    • California
      • Duarte, California, États-Unis, 91010
        • City of Hope
      • La Jolla, California, États-Unis, 92093
        • UC San Diego Moores Cancer Center
      • La Jolla, California, États-Unis, 92037-0845
        • UC San Diego Moores Cancer Center-Investigational Drug Services
      • La Jolla, California, États-Unis, 92037
        • UC San Diego Medical Center-La Jolla (Jacobs Medical Center/Thornton Hospital)
      • Los Angeles, California, États-Unis, 90095
        • Ronald Reagan UCLA Medical Center, Drug Information Center
      • Los Angeles, California, États-Unis, 90095
        • UCLA Hematology-Oncology Clinic
      • Los Angeles, California, États-Unis, 90095
        • Research Administration Office: Clinical Research Unit
      • Los Angeles, California, États-Unis, 90095
        • UCLA Bowyer Clinic
      • Palo Alto, California, États-Unis, 94304
        • Stanford University Medical Center
      • Palo Alto, California, États-Unis, 94305
        • Stanford University Medical Center
      • San Diego, California, États-Unis, 92103
        • UC San Diego Medical Center - Hillcrest
      • Santa Monica, California, États-Unis, 90404
        • Santa Monica UCLA Hematology & Oncology Clinic
      • Stanford, California, États-Unis, 94305
        • Stanford University Medical Center
    • District of Columbia
      • Washington, District of Columbia, États-Unis, 20007
        • MedStar Georgetown University Hospital
      • Washington, District of Columbia, États-Unis, 20007
        • Georgetown University Medical Center Department of Pharmacy, Research
    • Georgia
      • Atlanta, Georgia, États-Unis, 30322
        • Emory University Hospital
      • Atlanta, Georgia, États-Unis, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, États-Unis, 30322
        • The Emory Clinic
      • Atlanta, Georgia, États-Unis, 30322
        • Winship Cancer Institute
      • Atlanta, Georgia, États-Unis, 30322
        • The Emory Clinic, Building A
    • Massachusetts
      • Boston, Massachusetts, États-Unis, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, États-Unis, 02115
        • Brigham and Woman's Hospital
    • Michigan
      • Ann Arbor, Michigan, États-Unis, 48109
        • University of Michigan Health System
    • Missouri
      • Creve Coeur, Missouri, États-Unis, 63141
        • Siteman Cancer Center-West County
      • Saint Louis, Missouri, États-Unis, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, États-Unis, 63110
        • Barnes-Jewish Hospital
      • Saint Louis, Missouri, États-Unis, 63110
        • Washington University Infusion Center Pharmacy
      • Saint Louis, Missouri, États-Unis, 63110-1094
        • Barnes-Jewish Hospital
      • Saint Louis, Missouri, États-Unis, 63129
        • Siteman Cancer Center- South County
      • Saint Peters, Missouri, États-Unis, 63376
        • Siteman Cancer Center - St. Peters
    • New York
      • New York, New York, États-Unis, 10065
        • Memorial Sloan Kettering Cancer Center
    • Texas
      • Houston, Texas, États-Unis, 77030
        • The University of Texas - M.D. Anderson Cancer Center
      • San Antonio, Texas, États-Unis, 78229
        • South Texas Accelerated Research Therapeutics, LLC
    • Washington
      • Seattle, Washington, États-Unis, 98109
        • Seattle Cancer Care Alliance
      • Seattle, Washington, États-Unis, 98195
        • University of Washington Medical Center

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria

  • Portion A: Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy or B cell lymphoma, for which no curative therapy is available. Portion A expansion includes patients who have documented disease progression on a checkpoint inhibitor (anti CTLA 4, anti PD1/PD L1 antibodies) per RECIST criteria. Tumor types include metastatic melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NCSLC) and squamous cell carcinoma of the head and neck (SCCHN). Patients in the dose expansion stage are required to provide archival or baseline (obtained during the screening period) tumor biopsies.
  • Portion B: Histological confirmed relapsed or refractory CD20 positive NHL for which no curative therapy is available. Patients enrolled in the expansion cohort must have archival tissue available, sampled within 6 months of study entry. The Expansion cohort includes patients with FL or DLBCL with relapsed or refractory disease.
  • Measurable disease with at least one extranodal tumor mass >1.0 cm in the greatest transverse diameter (GTD) or in the case of malignant lymph nodes >1.5 cm in the GTD.
  • ECOG performance status of ≤ 1.
  • Adequate bone marrow function, for Portion A: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥100 x 109/L, hemoglobin >9.0 g/dL. For Portion B: ANC ≥ 1.0 x 109/L, platelet count ≥ 75 x 109/L, and hemoglobin ≥ 8.0 g/dL. In both cases, patients must be transfusion independent at least 14 days prior to screening.
  • Serum creatinine ≤ 2 x ULN or estimated creatinine clearance ≥ 50 ml/min.
  • Total serum bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert syndrome and AST and ALT ≤ 2.5 x ULN.

Exclusion Criteria

  • Patients with known symptomatic brain metastases requiring steroids.
  • Prior allogeneic hematopoietic stem cell transplant.
  • Immunosuppressive regimens involving systemic corticosteroids within 14 days before the first dose of study treatment.
  • Therapeutic or experimental monoclonal antibodies within 28 day or prior radiation therapy within 14 days of the first dose of study drug.
  • Autoimmune disorders and other diseases that compromise or impair the immune system.
  • Unstable or serious concurrent medical conditions in the previous 6 months.
  • Prior therapy with any anti CD137 monoclonal antibody.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Portion A
PF-05082566 single agent in patients with advanced cancer
Médicament: PF-05082566
Intravenous, Dose escalation, once per month
Médicament: PF-05082566
IV, Dose escalation, once per month
Expérimental: Portion B
PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma
Médicament: PF-05082566
Intravenous, Dose escalation, once per month
Médicament: PF-05082566
IV, Dose escalation, once per month
Médicament: rituximab
Intravenous, 375 mg/m2, once per week for 4 weeks
Autres noms:
  • Rituxan, MabThera

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A
Délai: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
DLT: Any of the following adverse events (AEs) occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 alone for Portion A and not related to progressive disease. Hematologic: Grade 4 neutropenia lasting more than (>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis. Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT). Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). Each cycle=28 days.
Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
Number of Participants With DLTs in First 2 Cycles of Portion B
Délai: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)
DLT: Any of the following AEs occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 in combination with rituximab for Portion B and not related to progressive disease. Hematologic: Grade 4 neutropenia lasting more than (>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis. Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT). Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). Each cycle=28 days.
Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A
Délai: Up to approximately 2 years
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; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs included both non-serious AEs and SAEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. Causality of AEs was determined by the investigator.
Up to approximately 2 years
Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade in Portion A
Délai: Up to approximately 2 years
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. Severity of AEs were graded according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
Up to approximately 2 years
Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
Délai: Up to approximately 2 years
Following hematology laboratory abnormalities were graded per NCI CTCAE version 4.03: anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets, white blood cells. The abnormalities with at least 1 participant are presented here.
Up to approximately 2 years
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
Délai: Up to approximately 2 years
Following chemistries laboratory abnormalities were graded per NCI CTCAE version 4.03: alanine aminotransferase (ALT), Alkaline phosphatase, Aspartate aminotransferase (AST), bilirubin (total), creatinine, gamma glutamyl transferase (GGT), hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. The abnormalities with at least 1 participant are presented here.
Up to approximately 2 years
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A
Délai: Up to approximately 2 years
For vital signs in Portion A, blood pressure and pulse rate were measured. Clinical significance was determined by the investigator.
Up to approximately 2 years
PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A
Délai: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose
Cmax of PF-05082566 was observed directly from data.
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose
PF-05082566 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A
Délai: Day 1 pre-dose of Cycle 2
Ctrough of PF-05082566 was observed directly from data.
Day 1 pre-dose of Cycle 2
PF-05082566 Time for Maximum Observed Serum Concentration (Tmax) in Portion A
Délai: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
Tmax of PF-05082566 was observed directly from data as time of Cmax.
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
PF-05082566 Area Under the Serum Concentration-Time Profile (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUClast) in Portion A
Délai: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
AUClast of PF-05082566 was determined by linear/log trapezoidal method.
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
PF-05082566 AUC From Time 0 to Infinity (AUCinf) in Portion A
Délai: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
AUCinf = AUClast + (Clast*/kel), where Clast* is the estimated concentration at the time of the last measurable concentration and kel is the terminal phase rate constant calculated as the absolute value of the slope of a linear regression during the terminal phase of the natural log-transformed concentration time profile.
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
PF-05082566 AUC From Time 0 to Time of Dosing Interval (AUCtau) in Portion A
Délai: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
PF-05082566 Clearance (CL) in Portion A
Délai: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2. It was reported in units of milliliter per hour per kilogram (mL/hr/kg).
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
PF-05082566 Volume of Distribution at Steady State (Vss) in Portion A
Délai: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
Number of Participants With Positive Anti-Drug Antibody (ADA) for PF-05082566 in Portion A
Délai: Up to approximately 2 years
ADA for PF-05082566 was detected using electrochemiluminescence assay. Positive ADA for PF-05082566: titer>=6.23.
Up to approximately 2 years
Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion A
Délai: Up to approximately 2 years
Categorical summarization criteria for QTc interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate): 1) absolute value of >450 to <=480 milliseconds (msec), >480 to <=500 msec, >500 msec; 2) a maximum change from baseline of >30 to <=60 msec or >60 msec.
Up to approximately 2 years
Percentage of Participants Achieving Objective Response Per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 in Portion A
Délai: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Objective response: confirmed best overall response (BOR) of complete response (CR) or partial response (PR) per RECIST version 1.1. BOR of CR: target lesions and non-target diseases achieved CR, without new lesions. BOR of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-progression of disease (non-PD), indeterminate or missing, and without new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and >=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Duration of Response in Portion A
Délai: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Duration of response: the time from first documentation of objective response (confirmed BOR of CR or PR per RECIST version 1.1) to the date of first documentation of objective progression of disease (PD) or death due to any cause. Objective PD per RECIST version 1.1: >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 millimeters (mm); or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions. This outcome measure reports the individual values for evaluable participants (instead of medians etc) due to the limited number of events.
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Time to Response in Portion A
Délai: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Time to response: the time from Cycle 1 Day 1 to the first documentation of objective response (confirmed BOR of CR or PR per RECIST version 1.1). BOR of CR: target lesions and non-target diseases achieved CR, without new lesions. BOR of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-PD, indeterminate or missing, and without new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes decreased to normal size); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and >=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Progression-Free Survival in Portion A
Délai: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Progression-free survival: the time from Cycle 1 Day 1 to the date of the first documentation of objective PD or death due to any cause, whichever occurred first. Objective PD per RECIST version 1.1: >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm; or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions.
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Overall Survival in Portion A
Délai: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Number of Participants With Treatment-Emergent AEs and SAEs in Portion B
Délai: Up to approximately 4 years
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; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs included both non-serious AEs and SAEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. Causality of AEs was determined by the investigator.
Up to approximately 4 years
Number of Participants With Treatment-Emergent AEs by Maximum NCI CTCAE Grade in Portion B
Délai: Up to approximately 4 years
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. Severity of AEs were graded according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
Up to approximately 4 years
Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B
Délai: Up to approximately 2 years
Following hematology laboratory abnormalities were graded per NCI CTCAE version 4.03: anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets, white blood cells. The abnormalities with at least 1 participant are presented here.
Up to approximately 2 years
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B
Délai: Up to approximately 2 years
Following chemistries laboratory abnormalities were graded per NCI CTCAE version 4.03: alanine aminotransferase (ALT), Alkaline phosphatase, Aspartate aminotransferase (AST), bilirubin (total), creatinine, gamma glutamyl transferase (GGT), hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. The abnormalities with at least 1 participant are presented here.
Up to approximately 2 years
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion B
Délai: Up to approximately 2 years
For vital signs in Portion B, blood pressure, pulse rate, and body temperature were measured. Clinical significance was determined by the investigator.
Up to approximately 2 years
PF-05082566 Cmax in Portion B
Délai: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
Cmax of PF-05082566 was observed directly from data.
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
PF-05082566 Ctrough in Portion B
Délai: Day 1 pre-dose of Cycle 2
Ctrough of PF-05082566 was observed directly from data.
Day 1 pre-dose of Cycle 2
PF-05082566 Tmax in Portion B
Délai: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
Tmax of PF-05082566 was observed directly from data as time of Cmax.
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
PF-05082566 AUClast in Portion B
Délai: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
AUClast of PF-05082566 was determined by linear/log trapezoidal method.
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
PF-05082566 AUCinf in Portion B
Délai: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.
AUCinf = AUClast + (Clast*/kel), where Clast* is the estimated concentration at the time of the last measurable concentration and kel is the terminal phase rate constant calculated as the absolute value of the slope of a linear regression during the terminal phase of the natural log-transformed concentration time profile.
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.
PF-05082566 AUCtau in Portion B
Délai: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
PF-05082566 CL in Portion B
Délai: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2.
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
PF-05082566 Vss in Portion B
Délai: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
Rituximab Cmax and Ctrough in Portion B
Délai: Day 1 pre-dose of Cycle 2
Cmax and Ctrough of rituximab were observed directly from data.
Day 1 pre-dose of Cycle 2
Number of Participants With Positive ADA for PF-05082566 and Rituximab in Portion B
Délai: Up to approximately 2 years
ADA for PF-05082566 and rituximab was detected using electrochemiluminescence assay. Positive ADA for PF-05082566: titer>=6.23. Positive ADA for rituximab: titer>=1.88.
Up to approximately 2 years
Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion B
Délai: Up to approximately 2 years
Categorical summarization criteria for QTc interval: 1) absolute value of >450 to <=480 milliseconds (msec), >480 to <=500 msec, >500 msec; 2) a maximum change from baseline of >30 to <=60 msec or >60 msec.
Up to approximately 2 years
Percentage of Participants Achieving Objective Response Per Cheson 2007 Criteria in Portion B
Délai: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Objective Response in Portion B was defined as BOR of CR or PR according to Cheson 2007 criteria. BOR of CR or PR per Cheson 2007: CR or PR of index lesions (complete disappearance of all detectable clinical and radiographic evidence of disease, all lymph nodes returned to normal size, spleen and/or liver if enlarged prior to therapy became normal or no longer palpable; or >=50% decrease in the sum of the product diameters [SPD] of up to 6 index lesions, no increase in size of other nodes, liver or spleen), without PD of non-index lesions (ie, without: new nonnodal lesion, new nodal lesion >=15 mm in greatest transverse diameter [GTD], unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), and without any new lesions.
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Duration of Response in Portion B
Délai: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Duration of Response in Portion B was defined, for participants with an objective response (BOR of CR or PR per Cheson 2007 criteria), as the time from first documentation of objective response to the date of first documentation of objective PD or death due to any cause. Objective PD per Cheson 2007 was defined as: PD of index lesions (>=50% increase in SPD of previously involved sites from nadir), or PD of non-index lesions (new nonnodal lesion, new nodal lesion >=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), or appearance of new lesions.
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Time to Response in Portion B
Délai: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Time to response in Portion B was defined, for participants with an objective response (BOR of CR or PR per Cheson 2007 criteria), as the time from Cycle 1 Day 1 to the first documentation of objective response. BOR of CR or PR per Cheson 2007: CR or PR of index lesions (complete disappearance of all detectable clinical and radiographic evidence of disease, all lymph nodes returned to normal size, spleen and/or liver if enlarged prior to therapy became normal or no longer palpable; or >=50% decrease in the SPD of up to 6 index lesions, no increase in size of other nodes, liver or spleen), without PD of non-index lesions (ie, without: new nonnodal lesion, new nodal lesion >=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), and without any new lesions.
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Progression-Free Survival in Portion B
Délai: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Progression-free survival in Portion B was defined as the time from Cycle 1 Day 1 to the date of the first documentation of objective PD (per Cheson 2007) or death due to any cause, whichever occurred first. Objective PD per Cheson 2007 was defined as: PD of index lesions (>=50% increase in SPD of previously involved sites from nadir), or PD of non-index lesions (new nonnodal lesion, new nodal lesion >=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), or appearance of new lesions.
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Overall Survival in Portion B
Délai: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)

Autres mesures de résultats

Mesure des résultats
Description de la mesure
Délai
Biomarkers Linked With Immunomodulation and Cytokine Release
Délai: Days 1, 14, 29 and 57
This was an exploratory endpoint and no data were collected.
Days 1, 14, 29 and 57
Exploratory Pharmacodynamic Biomarkers
Délai: Days 1 and 21
This was an exploratory endpoint and no data were collected.
Days 1 and 21
Patient-Reported Outcomes of PF-05082566 and Rituximab When Given in Combination in Follicular Lymphoma Participants
Délai: Up to 2 years
This was an exploratory endpoint and was not evaluated. Patient-reported outcome questionnaires were not completed as a result of administrative processing error.
Up to 2 years

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Pfizer

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Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

21 juin 2011

Achèvement primaire (Réel)

20 février 2019

Achèvement de l'étude (Réel)

20 février 2019

Dates d'inscription aux études

Première soumission

28 février 2011

Première soumission répondant aux critères de contrôle qualité

28 février 2011

Première publication (Estimation)

2 mars 2011

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

17 mars 2020

Dernière mise à jour soumise répondant aux critères de contrôle qualité

4 mars 2020

Dernière vérification

1 mars 2020

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • B1641001
  • 2011-002799-17 (Numéro EudraCT)

Plan pour les données individuelles des participants (IPD)

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NON

Description du régime IPD

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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