Fenretinide in Treating Patients With Refractory or Relapsed Hematologic Cancer

July 18, 2017 updated by: California Cancer Consortium

Phase I Trial of Intravenous Fenretinide (4-HPR) for Patients With Hematologic Malignancies

RATIONALE: 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. Giving fenretinide in a different way may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of intravenous fenretinide in treating patients with refractory or relapsed hematologic cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose of intravenous emulsified fenretinide in patients with refractory or relapsed hematologic malignancies.
  • Determine the toxic effects of this drug in these patients.
  • Determine the pharmacokinetics and in vivo activity of this drug in these patients.
  • Determine, preliminarily, disease or tumor response in patients treated with this drug.

OUTLINE: This is a pilot, dose-escalation, multicenter study.

Patients receive emulsified fenretinide IV continuously over 5 days. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete or partial response may continue to receive fenretinide at the discretion of the study chair.

Cohorts of 1 patient receive accelerated escalating doses of fenretinide until 2 patients experience moderate toxicity (cumulative across all dose levels) OR 1 patient experiences dose-limiting toxicity (DLT). After completion of the accelerated dose-escalation portion, the standard dose-escalation portion begins. Cohorts of 3-6 patients receive escalating doses of fenretinide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience DLT. At least 6 patients are treated at the MTD. An additional 12 patients are treated at the MTD.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • 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
    • California
      • Los Angeles, California, United States, 90089-9181
        • USC/Norris Comprehensive Cancer Center and Hospital
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
    • Texas
      • Houston, Texas, United States, 77030-4009
        • M. D. Anderson Cancer Center at University of Texas
      • Lubbock, Texas, United States, 79410-1894
        • Joe Arrington Cancer Research and Treatment 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

16 years to 118 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed diagnosis of 1 of the following hematologic malignancies:

    • Non-Hodgkin's lymphoma (NHL)
    • Hodgkin's lymphoma
    • Multiple myeloma
    • Acute lymphoblastic leukemia
    • Acute myeloid leukemia

    • Chronic hematologic malignancy with a poor prognosis (e.g., failed 3 prior standard therapies), including any of the following:

      • Chronic lymphocytic leukemia
      • Chronic myelogenous leukemia
      • Indolent NHL
      • Myeloproliferative disorders

  • Refractory or relapsed disease, as defined by 1 of the following:

    • Resistant to standard therapy for refractory or relapsed disease
    • Progressed after standard therapy for advanced disease
  • No effective treatment exists
  • Measurable or evaluable disease

  • No active CNS disease

    • Previously treated leptomeningeal disease or brain metastases allowed provided there is no evidence of remaining cancer by positron-emission tomography, MRI, or spinal fluid cytology

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 3 months

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3 (unless due to bone marrow involvement of disease)
  • Platelet count ≥ 75,000/mm^3 (unless due to bone marrow involvement of disease)
  • Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
  • No coagulation disorders

Hepatic

  • AST and ALT < 2.5 times upper limit of normal (ULN) (≤ 5 times ULN for patients with liver metastasis)
  • Bilirubin ≤ 1.5 times ULN

Renal

  • Creatinine ≤ 1.5 times ULN

Cardiovascular

  • No major cardiovascular disease

Pulmonary

  • No major respiratory disease

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method contraception prior to study entry, during study, and for at least 6 months after study participation
  • No uncontrolled systemic infection
  • No uncontrolled hypertriglyceridemia (i.e., triglyceride level > 500 mg/dL)
  • No known HIV positivity
  • No known allergy to egg products
  • No known familial hyperlipidemia disorders
  • No previously undiscovered hypertriglyceridemia
  • No poorly controlled diabetes

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • More than 2 weeks since prior chemotherapy except hydroxyurea

    • No concurrent hydroxyurea during study drug administration
  • No other concurrent anticancer chemotherapy

Endocrine therapy

  • No concurrent hormone-ablative agents
  • No concurrent steroids
  • No concurrent tamoxifen or any of its analogues

Radiotherapy

  • No prior cranial radiotherapy
  • More than 2 weeks since prior radiotherapy

Surgery

  • More than 20 days since prior surgery except for biopsy

Other

  • Recovered from all prior therapy
  • More than 2 weeks since prior investigational agents
  • No other concurrent investigational agents
  • No other concurrent antineoplastic therapy
  • No other concurrent antioxidants
  • No concurrent herbal or other alternative therapies

  • No concurrent vitamin supplements (e.g., vitamin A, ascorbic acid, or vitamin E)

    • Standard dose multivitamin allowed

  • No other concurrent medications that may act as modulators of intracellular ceramide levels or ceramide cytotoxicity, sphingolipid transport, or p-glycoprotein or multidrug resistance protein 1 (MRP1) drug/lipid transporters, including any of the following:

    • Cyclosporine or any of its analogues
    • Verapamil
    • Ketoconazole
    • Chlorpromazine
    • Mifepristone
    • Indomethacin
    • Sulfinpyrazone

  • No concurrent medications that may cause pseudotumor cerebri, including any of the following:

    • Tetracycline
    • Nalidixic acid
    • Nitrofurantoin
    • Phenytoin
    • Sulfonamides
    • Lithium
    • Amiodarone
  • No concurrent medication to control hypertriglyceridemia

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine the maximum tolerated dose of fenretinide
Time Frame: participants will be followed for the duration of cycle 1, which is expected to be 3 weeks.
participants will be followed for the duration of cycle 1, which is expected to be 3 weeks.
To describe the toxicities of fenretinide
Time Frame: participants will be followed for the duration of treatment, which is expected to be 18 weeks or less
participants will be followed for the duration of treatment, which is expected to be 18 weeks or less

Collaborators and Investigators

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

Sponsor

California Cancer Consortium

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Ann Mohrbacher, MD, University of Southern California

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

February 1, 2005

Primary Completion (Actual)

April 1, 2017

Study Completion (Actual)

April 1, 2017

Study Registration Dates

First Submitted

March 3, 2005

First Submitted That Met QC Criteria

March 3, 2005

First Posted (Estimate)

March 4, 2005

Study Record Updates

Last Update Posted (Actual)

July 19, 2017

Last Update Submitted That Met QC Criteria

July 18, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000413887
  • P30CA033572 (U.S. NIH Grant/Contract)
  • CCC-PHI-42
  • NCI-6528
  • LAC-USC-0C-04-3
  • NCI-06-C-0227
  • NCI-P6820

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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