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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01307267
First received: February 28, 2011
Last updated: August 26, 2015
Last verified: August 2015
  Purpose

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).


Condition Intervention Phase
Lymphoma, Non-Hodgkin
Drug: PF-05082566
Drug: rituximab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: First 2 cycles (56 days) of treatment ] [ Designated as safety issue: Yes ]
    Dose Limiting Toxicities (DLTs) of PF-05082566 as single agent

  • Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: First 2 cycles (56 days) of treatment ] [ Designated as safety issue: Yes ]
    Dose Limiting Toxicities (DLTs) of PF-05082566 in combination with rituximab


Secondary Outcome Measures:
  • Pharmacokinetics (Tmax) of PF-05082566 and rituximab when given in combination [ Time Frame: Days -7, 0, 1, 3, 7, 1, 22, 29, 36, 43, 50, 57, 78, 85, 112 and 141, followed by every 28 days during the therapy up to 2 years. ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of PF-05082566 and rituximab when given in combination

  • Pharmacokinetics (Tmax) of PF-05082566 as a single agent [ Time Frame: Days 1, 3, 8, 15, 22, 29, 31, 36, 43, 50, 57, 64, 71, 78, 85, 87, 112, followed by every 28 days during the therapy up to 2 years, then Days 28, 57 and 85 after the administration of the last dose. ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of PF-05082566 and rituximab when given in combination

  • Presence of Anti-Drug Antibodies against PF-05082566 (Portion A) [ Time Frame: Days 1, 8, 15, 29, 36, 43, 57, 71, 127, 145 and every 28 days up to 2 years during the treatment and end of treatment ] [ Designated as safety issue: Yes ]
  • Presence of Anti-Drug Antibodies against PF-05082566 and rituximab (Portion B) [ Time Frame: Every 28 days during the treatment up to 2 years and at the end of treatment ] [ Designated as safety issue: Yes ]
  • Analysis of biomarkers linked with immunomodulation/cytokine release [ Time Frame: Days 1, 14, 29 and 57 ] [ Designated as safety issue: Yes ]
  • Analysis of exploratory pharmacodynamic biomarkers [ Time Frame: Days 1 and 21 ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by: Objective Response Rate of PF-05082566 as a single agent [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by Objective Response Rate of PF-05082566 and rituximab when given in combination [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (Cmax) of PF-05082566 and rituximab when given in combination [ Time Frame: Days -7, 0, 1, 3, 7, 1, 22, 29, 36, 43, 50, 57, 78, 85, 112 and 141, followed by every 28 days during the therapy up to 2 years. ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of PF-05082566 and rituximab when given in combination

  • Pharmacokinetics (AUC) of PF-05082566 and rituximab when given in combination [ Time Frame: Days -7, 0, 1, 3, 7, 1, 22, 29, 36, 43, 50, 57, 78, 85, 112 and 141, followed by every 28 days during the therapy up to 2 years. ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of PF-05082566 and rituximab when given in combination

  • Pharmacokinetics (Cmax) of PF-05082566 as a single agent [ Time Frame: Days 1, 3, 8, 15, 22, 29, 31, 36, 43, 50, 57, 64, 71, 78, 85, 87, 112, followed by every 28 days during the therapy up to 2 years, then Days 28, 57 and 85 after the administration of the last dose. ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of PF-05082566 and rituximab when given in combination

  • Pharmacokinetics (AUC) of PF-05082566 as a single agent [ Time Frame: Days 1, 3, 8, 15, 22, 29, 31, 36, 43, 50, 57, 64, 71, 78, 85, 87, 112, followed by every 28 days during the therapy up to 2 years, then Days 28, 57 and 85 after the administration of the last dose. ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of PF-05082566 and rituximab when given in combination

  • Efficacy as measured by: Duration of Response of PF-05082566 and rituximab when given in combination [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by Progression Free Survival of PF-05082566 and rituximab when given in combination [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by Overall Survival of PF-05082566 and rituximab when given in combination [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by Duration of Response of PF-05082566 as a single agent [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by Progression Free Survival of PF-05082566 given as a single agent [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by Overall Survival of PF-05082566 given as a single agent [ Time Frame: Assessed once every 8 weeks up to 2 years during the study treatment and every 2 to 4 months thereafter until progression ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 161
Study Start Date: June 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
PF-05082566 single agent in patients with advanced cancer
Drug: PF-05082566
Intravenous, Dose escalation, once per month
Experimental: B
PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma
Drug: rituximab
Intravenous, 375 mg/m2, once per week for 4 weeks
Other Name: Rituxan, MabThera
Drug: PF-05082566
IV, Dose escalation, once per month

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 B: Histological confirmed relapsed or refractory CD20 positive NHL for which no curative therapy is available, including SLL/CLL with nodal disease (not including SLL/CLL with >10,000 lymphocytes/μL, prolymphocytic leukemia, hairy cell leukemia, heavy chain disease, plasma cell myeloma, solitary plasmacytoma of bone, extraosseous plasmacytoma, lymphomatoid granulomatosis, and large B cell lymphoma arising in Castleman disease). Additionally, patients enrolled in the MTD expansion cohort must have tumor accessible for repeat biopsy (core needle biopsy preferred).
  • Age 18 years or older. Eastern Cooperative Oncology Group (ECOG) performance status of greater than or equal to 1.
  • Adequate bone marrow function, for Portion A defined as absolute neutrophil count (ANC) ≥1.5 x 109/L (≥1,500/μL), platelet count ≥100 x 109/L (≥100,000/μL), and hemoglobin >9.0 g/dL (>5.6 mmol/L), and for Portion B as ANC ≥1.0 x 109/L (≥1,000/uL), platelet count ≥75 x 109/L (≥75000/μL), and hemoglobin >9.0 g/dL (>5.6 mmol/L). (For patients enrolled in Japan, hemoglobin >8.5 g/dL (>5.3 mmol/L). In both cases, patients must be transfusion independent (ie, no blood product transfusions for a period of at least 14 days prior to screening).
  • Adequate Renal Function, including serum creatinine ≤1.5 x upper limit of normal (ULN) or estimated creatinine clearance ≥60 ml/min as calculated using the method standard for the institution.
  • Adequate Liver Function, including: a) Total serum bilirubin ≤1.5 x ULN unless the patient has documented Gilbert syndrome; b) Aspartate and Alanine Aminotransferase (AST and ALT) ≤2.0 x ULN; c) Alkaline phosphatase ≤2.5 x ULN (≤5 x ULN in case of bone metastasis).
  • Adequate Cardiac Function, as measured by left ventricular ejection fraction (LVEF) that is greater than 40%, or the presence of New York Heart Association (NYHA) classification of no greater than stage II congestive heart failure.

Exclusion Criteria:

  • Therapeutic or experimental monoclonal antibodies in last 60 days prior to first dose of study drug.
  • Prior therapy with a compound of the same mechanism (interacting with 4-1BB)
  • Chemotherapy, cancer immunosuppressive therapy, growth factors, systemic steroids, or investigational agents within 28 days before the first dose of study treatment (for the purposes of this protocol, study treatment includes rituximab in Portion B).
  • Prior allogeneic hematopoietic stem cell transplant.
  • Central nervous system (CNS) primary or CNS metastatic malignancies.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01307267

Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021

Locations
United States, California
Moores UC San Diego Cancer Center Not yet recruiting
La Jolla, California, United States, 92093
UC San Diego Medical Center - La Jolla (Thornton Hospital) Not yet recruiting
La Jolla, California, United States, 92037-0845
For Drug Shipment: Moores UC San Diego Cancer Center - Investigational Drug Services Not yet recruiting
La Jolla, California, United States, 92037-0845
UCLA Hematology-Oncology Clinic Recruiting
Los Angeles, California, United States, 90095
Ronald Reagan UCLA Medical Center, Drug Information Center Recruiting
Los Angeles, California, United States, 90095
UCLA Bowyer Clinic Recruiting
Los Angeles, California, United States, 90095
UCLA Department of Medicine Recruiting
Los Angeles, California, United States, 90024
Stanford University Medical Center Active, not recruiting
Palo Alto, California, United States, 94304
UC San Diego Medical Center - Hillcrest Not yet recruiting
San Diego, California, United States, 92103
Stanford University Medical Center Active, not recruiting
Stanford, California, United States, 94305-5151
Stanford University Medical Center Active, not recruiting
Stanford, California, United States, 94305
United States, District of Columbia
Georgetown University Hospital Recruiting
Washington, District of Columbia, United States, 20007
Drug Shipment Address and Pharmacist Designees Recruiting
Washington, District of Columbia, United States, 20007-2197
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Barnes-Jewish Hospital Recruiting
St. Louis, Missouri, United States, 63110-1094
Barnes-Jewish Hospital Recruiting
St. Louis, Missouri, United States, 63110
Washington University Infusion Center Pharmacy Recruiting
St. Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10022
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Washington
University of Washington/Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
France
Centre d'investigation clinique Terminated
RENNES cedex 9, France, 35033
Japan
National Cancer Center Hospital East Recruiting
Kashiwa, Chiba, Japan, 277-8577
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01307267     History of Changes
Other Study ID Numbers: B1641001, 2011-002799-17
Study First Received: February 28, 2011
Last Updated: August 26, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Phase 1
Non-Hodgkin's Lymphoma
Advanced malignancies

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015