Fenretinide in Treating Patients With Refractory or Relapsed Hematologic Cancer

Sponsor

California Cancer Consortium (Other)

Overall Status

Completed

CT.gov ID

NCT00104923

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

145.9

Duration (Months)

7.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm	Drug: fenretinide	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

29 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2005

Actual Primary Completion Date :

Apr 1, 2017

Actual Study Completion Date :

Apr 1, 2017

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
2	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland	United States	20892-1182
3	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
4	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410-1894