Bexarotene and GM-CSF in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

NCT ID: NCT00425477

Last Updated: 2018-10-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2016-09-30

Brief Summary

RATIONALE: Bexarotene may help cancer or abnormal cells become more like normal cells, and to grow and spread more slowly. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving bexarotene together with GM-CSF may be an effective treatment for myelodysplastic syndrome (MDS) or acute myeloid leukemia.

PURPOSE: This phase II trial is studying how well giving bexarotene together with GM-CSF works in treating patients with MDS or acute myeloid leukemia.

Detailed Description

OBJECTIVES:

Primary

• Assess the clinical response in patients with myelodysplastic syndromes or acute myeloid leukemia treated with bexarotene and sargramostim (GM-CSF).

Secondary

• Determine the clinical activity of this regimen, in terms of transfusion requirements, in these patients.
• Determine the biological activity of this regimen, in terms of biological markers and cytogenetic abnormalities, in these patients.
• Assess the toxicity profile of this regimen in these patients.

OUTLINE: Patients receive oral bexarotene and sargramostim (GM-CSF) subcutaneously on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Blood and bone marrow samples are collected at baseline and after 1 or 2 courses of study therapy. Samples are examined by flow cytometry for laboratory studies, including biological markers, and by fluorescent in situ hybridization (FISH) for cytogenetic changes.

After completion of study treatment, patients are followed periodically for 6 months.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bexarotene + GM-CSF

BEX and GM-CSF were administered in 4 week cycles. BEX was given orally with food daily for 28 days at the FDA-approved dose for treatment of CTCL of 300 mg/m2 and GM-CSF was given at a daily dose of 125 µg/m2 subcutaneously for 28 days.

Group Type: EXPERIMENTAL

sargramostim

Intervention Type: BIOLOGICAL

bexarotene

Intervention Type: DRUG

cytogenetic analysis

Intervention Type: GENETIC

fluorescence in situ hybridization

Intervention Type: GENETIC

flow cytometry

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

biopsy

Intervention Type: PROCEDURE

Interventions

sargramostim

Intervention Type: BIOLOGICAL

bexarotene

Intervention Type: DRUG

cytogenetic analysis

Intervention Type: GENETIC

fluorescence in situ hybridization

Intervention Type: GENETIC

flow cytometry

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

biopsy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis (confirmed by bone marrow aspirate and/or biopsy) of 1 of the following:

• Myelodysplastic syndromes of 1 of the following cell types:

• Refractory anemia (RA) with ringed sideroblasts
• Refractory cytopenia with multilineage dysplasia (RCMD)
• RCMD and ringed sideroblasts
• RA with excess blasts-1
• RA with excess blasts-2
• Myelodysplastic syndromes, unclassified
• Chronic myelomonocytic leukemia
• Relapsed or refractory acute myeloid leukemia (AML), meeting 1 of the following criteria:

• Recurrent genetic abnormalities (11q23 [MLL] abnormalities)
• Multilineage dysplasia
• Therapy-related AML
• Not otherwise categorized, including any of the following:

• M0 minimally differentiated
• M1 without maturation
• M2 with maturation
• M4 myelomonocytic leukemia
• M5 monoblastic/monocytic leukemia
• M6 erythroid leukemia
• M7 megakaryoblastic leukemia
• Newly diagnosed untreated AML allowed provided patient does not qualify for or refused potentially curative intensive chemotherapeutic regimens
• No RA with 5q-syndrome
• No peripheral leukemia with blast count > 30,000/mm³ (uncontrolled with hydroxyurea)
• Relatively stable bone marrow function for > 7 days (i.e., no WBC doubling to > 10,000/mm^3)
• No acute promyelocytic leukemia
• No clinical symptoms of active CNS disease (if CNS disease is suspected, patient must have lumbar puncture with negative cytology)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Creatinine ≤ 2.0 mg/dL
• Bilirubin ≤ 1.6 mg/dL (unless secondary to hemolysis)
• AST and ALT ≤ 4 times upper limit of normal (unless disease related)
• Hemoglobin ≥ 8 g/dL (transfusions allowed)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• No untreated positive blood cultures or progressive infection as assessed by radiographic studies
• No history of intolerance to sargramostim (GM-CSF)

PRIOR CONCURRENT THERAPY:

• Recovered from prior therapy
• At least 2 weeks since prior treatment for myeloid disorder, including any of the following:

• Chemotherapy
• Hematopoietic growth factors
• Biologic therapy (e.g., monoclonal antibodies)
• Hydroxyurea for patients with WBC > 10,000/mm^3 allowed
• No concurrent vitamin A supplementation
• No concurrent gemfibrozil

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

B. Douglas Smith, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JHOC-J0675

Identifier Type: -

Identifier Source: secondary_id

JHOC-NA_00003076

Identifier Type: -

Identifier Source: secondary_id

J0675 CDR0000525989

Identifier Type: -

Identifier Source: org_study_id