Fenretinide in Treating Patients With Refractory or Relapsed Hematologic Cancer

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00104923
• Other study ID #: CDR0000413887
• Secondary ID: P30CA033572CCC-P
• Status: Completed
• Phase: Phase 1
• First received: March 3, 2005
• Last updated: July 18, 2017
• Start date: February 2005
• Est. completion date: April 2017

Study information

• Verified date: July 2017
• Source: California Cancer Consortium
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myeloproliferative Disorders
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

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

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas

Sponsors (2)

Lead Sponsor	Collaborator
California Cancer Consortium	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	To describe the toxicities of fenretinide		participants will be followed for the duration of treatment, which is expected to be 18 weeks or less