Fenretinide and Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma

September 30, 2014 updated by: National Cancer Institute (NCI)

A Phase I-II Trial of Fenretinide (4-HPR) + Rituximab in Patients With B-cell Lymphoma

This phase I/II trial is studying the side effects and best dose of fenretinide and to see how well it works when given together with rituximab in treating patients with B-cell non-Hodgkin lymphoma. Drugs used in chemotherapy, such as fenretinide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Giving fenretinide together with rituximab may kill more cancer cells.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety of fenretinide delivered in a 5 of 7 day regimen. (Phase I) II. To estimate the efficacy (response rates) of fenretinide + rituximab in patients with B-cell non-Hodgkin lymphoma (NHL). (Phase II)

SECONDARY OBJECTIVES:

I. To perform pharmacokinetic studies on patients receiving fenretinide. (Phase I) II. To determine the intratumoral concentrations of fenretinide. (Phase I) III. To evaluate the in vivo mechanism of action of fenretinide. (Phase I) IV. To identify the predictors of response to fenretinide. (Phase I) V. To estimate the response rates, positron emission tomography (PET) response, overall survival (OS), progression-free survival (PFS), time to progression (TTP), and disease-free survival (DFS) of patients treated on this study. (Phase I) VI. To estimate the overall survival (OS), progression-free survival (PFS), time to progression (TTP), disease-free survival (DFS), and PET responses of patients treated on this study. (Phase II) VII. To perform pharmacokinetic studies on patients receiving fenretinide. (Phase II) VIII. To determine the intratumoral concentration of fenretinide. (Phase II) IX. To identify the predictors of response to fenretinide and fenretinide + rituximab in B-NHL. (Phase II) X. To evaluate the in vivo mechanism of action of fenretinide in B-NHL. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of fenretinide followed by a phase II study.

PHASE I: Patients receive fenretinide orally (PO) twice daily (BID) on days 1-5. Treatment repeats weekly for at least 4 weeks in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab intravenously (IV) once weekly in weeks 5-8. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have a confirmed cluster of differentiation (CD) 20+ lymphoid malignancy

    • All patients with indolent NHL (including Follicular, Marginal Zone, small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL), lymphoplasmacytoid/Waldenström's, nodular lymphocyte predominant Hodgkins) are potentially eligible
    • Patients with Aggressive Lymphoma (including diffuse large B-cell, Burkitt's, Burkitt's-like, B-lymphoblastic) may be considered for this protocol only if unable or unwilling to receive potentially curative intensive therapy
    • All Mantle Cell Lymphoma patients are potentially eligible
  • The World Health Organization (WHO) classification of patient's malignancy must be provided
  • Patients must have a Southwest Oncology Group (SWOG)/Eastern Cooperative Oncology Group (ECOG) of =< 2
  • Patients should have an expected survival if untreated of at least 60 days
  • Patients must be expected to complete at least 8 weeks of therapy
  • Serum bilirubin less than 2 times the upper limit of normal and no other serious medical condition
  • Creatinine less than 2 times the upper limit of normal and no other serious medical condition
  • Patients must have measurable disease defined as lesions that can be accurately measured in two dimensions by computed tomography (CT), magnetic resonance imaging (MRI), medical photograph (skin or oral lesion), plain x-ray, or other conventional technique and a greatest transverse diameter of 1 cm or greater; or palpable lesions with both diameters >= 2 cm or evaluable disease in the bone marrow; patients must have a CT of chest, abdomen, and pelvis within 28 days of enrollment; patients with evidence of adenopathy in the neck must have a CT of the neck; (Note: Patients with CLL do not need to have radiographically measurable disease as this is not required to measure response in this disease setting)
  • All patients with an unknown prior bone marrow status or history of bone marrow involvement must have a bone marrow aspirate and biopsy within 28 days of enrollment and no intervening anticancer therapy
  • All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines

Exclusion Criteria:

  • Patients known to be human immunodeficiency virus (HIV) positive
  • Patients with evidence of active central nervous system malignancy
  • Pregnant or nursing women
  • Men or women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
  • Concurrent anti-neoplastic therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment (fenretinide, rituximab)

PHASE I: Patients receive fenretinide PO BID on days 1-5. Treatment repeats weekly for at least 4 weeks in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab IV once weekly in weeks 5-8. Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: fenretinide
Given PO
Other Names:
  • fenretinimide
  • McN-R-1967
Drug: rituximab
Given IV
Other Names:
  • Rituxan
  • Mabthera
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety, in Terms of Dose-limiting Toxicity (DLT) of 2 Daily Doses of Single Agent Fenretinide (Phase I)
Time Frame: Number of participants that experienced a dose-limiting toxicity

A group of 3 patients would start treatment ast the dose of 900mg/m^2 BID, and if none of the 3 experienced a DLT, another 3 would then be treated at that dose. Dose Limiting Toxicity was defined as any related toxicity of grade 4 or 5 on or before the completion of 4 weeks of therapy.

Per response evaluation criteria 1999 Cheson Response Criteria for Malignant Lymphoma (CHESON99) for target lesions assessed by either CT or MRI:

Complete Response (CR): Complete disappearance of all measurable and non-measurable disease; Complete Response Unconfirmed (CRU): Complete disappearance of all measurable and non-measurable disease, with the exception of all residual nodal masses >1.5cm in Greatest Transverse Diameter (GTD) reduced by 75% in Sum of the Product of the greatest Diameters (SPD); Partial Response (PR): 50% decrease in the SPD.
Number of participants that experienced a dose-limiting toxicity
Response Rates of B-Non-Hodgkin Lymphoma to the Combination of Rituximab and Fenretinide (Phase II)
Time Frame: Up to 7 years
The trial was stratified into rituximab-naïve and rituximab pre-treated patients, and the target response rates for these groups were expected to be 30% and 10%, respectively. The numbers reported below are subjects who achieved a response of partial response or better.
Up to 7 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Ajay Gopal, University of Washington

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2005

Primary Completion (ACTUAL)

July 1, 2013

Study Completion (ACTUAL)

July 1, 2013

Study Registration Dates

First Submitted

February 6, 2006

First Submitted That Met QC Criteria

February 6, 2006

First Posted (ESTIMATE)

February 7, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

October 6, 2014

Last Update Submitted That Met QC Criteria

September 30, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00104 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • CDR0000456502 (OTHER: NCI)
  • UWCC-UW-6071 (OTHER: Fred Hutchinson Cancer Research Center)
  • UWCC-06-0644-H/A (OTHER: Fred Hutchinson Cancer Research Center)
  • UWCC-6071 (OTHER: Fred Hutchinson Cancer Research Center)
  • FHCRC-6071 (OTHER: Fred Hutchinson Cancer Research Center)
  • 6071 (OTHER: University of Washington Medical Center)
  • 6957 (OTHER: CTEP)
  • R21CA119519 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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