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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete and partial response at 2 months following study completion

Outcome Time Frame:

continuing

Safety Issue:

No

Principal Investigator

Ann Mohrbacher, MD

Investigator Role:

Study Chair

Investigator Affiliation:

USC/Norris Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000413887

NCT ID:

NCT00104923

Start Date:

February 2005

Completion Date:

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • 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
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • recurrent marginal zone lymphoma
  • splenic marginal zone lymphoma
  • recurrent adult acute myeloid leukemia
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myeloproliferative Disorders

Name

Location

Joe Arrington Cancer Research and Treatment CenterLubbock, Texas  79410-1894
USC/Norris Comprehensive Cancer Center and HospitalLos Angeles, California  90033-0804
M. D. Anderson Cancer Center at University of TexasHouston, Texas  77030-4009
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral OfficeBethesda, Maryland  20892-1182