Fenretinide in Treating Patients With Refractory or Relapsed Hematologic Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
California Cancer Consortium
ClinicalTrials.gov Identifier:
NCT00104923
First received: March 3, 2005
Last updated: July 29, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Drug: fenretinide
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Intravenous Fenretinide (4-HPR) for Patients With Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by California Cancer Consortium:

Primary Outcome Measures:
  • Complete and partial response at 2 months following study completion [ Time Frame: continuing ] [ Designated as safety issue: No ]
  • Stable and progressive disease at 2 months following study completion [ Time Frame: continuing ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: February 2005
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: fenretinide
    Current dose level as an IV continuous infusion via central line over 5 days. Cycle is repeated every 3 weeks for up to 6 cycles
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.

  Eligibility

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

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
  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: NCT00104923

Locations
United States, California
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Joe Arrington Cancer Research and Treatment Center
Lubbock, Texas, United States, 79410-1894
Sponsors and Collaborators
California Cancer Consortium
Investigators
Study Chair: Ann Mohrbacher, MD University of Southern California
  More Information

Additional Information:
No publications provided

Responsible Party: California Cancer Consortium
ClinicalTrials.gov Identifier: NCT00104923     History of Changes
Other Study ID Numbers: CDR0000413887, P30CA033572, CCC-PHI-42, NCI-6528, LAC-USC-0C-04-3, NCI-06-C-0227, NCI-P6820
Study First Received: March 3, 2005
Last Updated: July 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by California Cancer Consortium:
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent small lymphocytic lymphoma
recurrent mantle cell lymphoma
Waldenstrom macroglobulinemia
adult grade III lymphomatoid granulomatosis
recurrent adult grade III lymphomatoid granulomatosis
secondary acute myeloid leukemia
recurrent adult Burkitt lymphoma
recurrent adult immunoblastic large cell lymphoma
refractory chronic lymphocytic leukemia
recurrent adult lymphoblastic lymphoma
recurrent adult Hodgkin lymphoma
refractory multiple myeloma
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
chronic eosinophilic leukemia
primary myelofibrosis
chronic neutrophilic leukemia
essential thrombocythemia
polycythemia vera
stage II multiple myeloma
stage III multiple myeloma
recurrent adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Neoplasms
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myeloproliferative Disorders
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Fenretinide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2014