Brief Title
Fenretinide and Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma
Official Title
A Phase I-II Trial of Fenretinide (4-HPR) + Rituximab in Patients With B-cell Lymphoma
Brief Summary
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.
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 Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Safety, in Terms of Dose-limiting Toxicity (DLT) of 2 Daily Doses of Single Agent Fenretinide (Phase I)
Condition
Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma
Intervention
fenretinide
Study Arms / Comparison Groups
Treatment (fenretinide, rituximab)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
32
Start Date
October 2005
Completion Date
July 2013
Primary Completion Date
July 2013
Eligibility 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Ajay Gopal, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00288067
Organization ID
NCI-2009-00104
Secondary IDs
NCI-2009-00104
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Ajay Gopal, Principal Investigator, University of Washington
Verification Date
January 2014