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 July 2014 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01307267
First received: February 28, 2011
Last updated: July 10, 2014
Last verified: July 2014
  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 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 of treatment ] [ Designated as safety issue: Yes ]
    Dose Limiting Toxicities (DLTs) of PF-05082566 in combination with rituximab


Secondary Outcome Measures:
  • Pharmacokinetics of PF-05082566 and rituximab when given in combination [ Time Frame: Cycles 1 through 4 and end of treatment ] [ Designated as safety issue: Yes ]
    Pharmacokinetics of PF-05082566 and rituximab when given in combination

  • Pharmacokinetics of PF-05082566 as a single agent [ Time Frame: Cycles 1 through 4 and end of treatment ] [ 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: Cycles 1 through 4 and end of treatment ] [ Designated as safety issue: Yes ]
  • Presence of Anti-Drug Antibodies against PF-05082566 and rituximab (Portion B) [ Time Frame: Cycles 1 through 4 and end of treatment ] [ Designated as safety issue: Yes ]
  • Analysis of biomarkers linked with immunomodulation/cytokine release [ Time Frame: Cycles 1 through 4 and end of treatment ] [ Designated as safety issue: Yes ]
  • Analysis of exploratory pharmacodynamic biomarkers [ Time Frame: Cycles 1 through 4 and end of treatment ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by: Objective Response Rate, Duration of Response, Progression Free Survival and Overall Survival of PF-05082566 as a single agent [ Time Frame: Assessed once every 8 weeks ] [ Designated as safety issue: Yes ]
  • Efficacy as measured by: Objective Response Rate, Duration of Response, Progression Free Survival and Overall Survival of PF-05082566 and rituximab when given in combination [ Time Frame: Assessed once every 8 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 78
Study Start Date: June 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (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). 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
Pfizer Investigational Site Recruiting
Stanford, California, United States, 94305
Pfizer Investigational Site Recruiting
Stanford, California, United States, 94305-5151
United States, District of Columbia
Pfizer Investigational Site Recruiting
Washington, District of Columbia, United States, 20007
Pfizer Investigational Site Recruiting
Washington, District of Columbia, United States, 20007-2197
United States, Missouri
Pfizer Investigational Site Recruiting
St. Louis, Missouri, United States, 63110
Pfizer Investigational Site Recruiting
St. Louis, Missouri, United States, 63110-1094
United States, New York
Pfizer Investigational Site Recruiting
New York, New York, United States, 10022
Pfizer Investigational Site Recruiting
New York, New York, United States, 10065
United States, Washington
Pfizer Investigational Site Recruiting
Seattle, Washington, United States, 98109
France
Pfizer Investigational Site Recruiting
RENNES cedex 9, France, 35033
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
Study First Received: February 28, 2011
Last Updated: July 10, 2014
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
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 24, 2014