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

This study has been terminated.
(NCI stopped supplying fenretinide in November of 2012.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00288067
First received: February 6, 2006
Last updated: September 30, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma
B-cell Chronic Lymphocytic Leukemia
Contiguous Stage II Adult Burkitt Lymphoma
Contiguous Stage II Adult Diffuse Large Cell Lymphoma
Contiguous Stage II Adult Lymphoblastic Lymphoma
Contiguous Stage II Grade 1 Follicular Lymphoma
Contiguous Stage II Grade 2 Follicular Lymphoma
Contiguous Stage II Mantle Cell Lymphoma
Stage II Marginal Zone Lymphoma
Stage II Small Lymphocytic Lymphoma
Extranodal Marginal Zone B-cell Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Noncontiguous Stage II Adult Burkitt Lymphoma
Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
Noncontiguous Stage II Adult Lymphoblastic Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Splenic Marginal Zone Lymphoma
Stage I Adult Burkitt Lymphoma
Stage I Adult Diffuse Large Cell Lymphoma
Stage I Adult Hodgkin Lymphoma
Stage I Adult Lymphoblastic Lymphoma
Stage I Chronic Lymphocytic Leukemia
Stage I Grade 1 Follicular Lymphoma
Stage I Grade 2 Follicular Lymphoma
Stage I Small Lymphocytic Lymphoma
Stage II Adult Hodgkin Lymphoma
Stage II Chronic Lymphocytic Leukemia
Stage III Adult Burkitt Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Hodgkin Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Chronic Lymphocytic Leukemia
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Small Lymphocytic Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Hodgkin Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Waldenström Macroglobulinemia
Drug: fenretinide
Drug: rituximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I-II Trial of Fenretinide (4-HPR) + Rituximab in Patients With B-cell Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

    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.


  • Response Rates of B-Non-Hodgkin Lymphoma to the Combination of Rituximab and Fenretinide (Phase II) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 32
Study Start Date: October 2005
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan

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.

  Eligibility

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

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
  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: NCT00288067

Locations
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Investigators
Principal Investigator: Ajay Gopal University of Washington
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00288067     History of Changes
Other Study ID Numbers: NCI-2009-00104, NCI-2009-00104, CDR0000456502, UWCC-UW-6071, UWCC-06-0644-H/A, UWCC-6071, FHCRC-6071, 6071, 6957, R21CA119519
Study First Received: February 6, 2006
Results First Received: January 8, 2014
Last Updated: September 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hodgkin Disease
Burkitt Lymphoma
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases
DNA Virus Infections
Epstein-Barr Virus Infections
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Herpesviridae Infections
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Experimental
Neoplasms, Plasma Cell

ClinicalTrials.gov processed this record on October 23, 2014