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

Phase 2

Completed

• Conditions: Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases
• Interventions: Biological: sargramostim; Drug: bexarotene; Genetic: cytogenetic analysis; Genetic: fluorescence in situ hybridization; Other: flow cytometry; Other: laboratory biomarker analysis; Procedure: biopsy

• Registration Number: NCT00425477
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Study Timeline

• Study Start: 2006-11
• Study First Submitted: 2007-01-19
• Study First Submitted QC: 2007-01-19
• Study First Posted: 2007-01-23
• Primary Completion: 2016-09-30
• Study Completion: 2016-09-30
• Results First Submitted: 2018-01-31
• Results First Submitted QC: 2018-08-06
• Status Verified: 2018-09
• Results First Posted: 2018-09-05
• Last Update Submitted: 2018-09-07
• Last Update Posted: 2018-10-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bexarotene + GM-CSF	sargramostim	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.
Bexarotene + GM-CSF	bexarotene	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.
Bexarotene + GM-CSF	cytogenetic analysis	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.
Bexarotene + GM-CSF	fluorescence in situ hybridization	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.
Bexarotene + GM-CSF	flow cytometry	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.
Bexarotene + GM-CSF	laboratory biomarker analysis	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.
Bexarotene + GM-CSF	biopsy	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.

Primary Outcome Measures

Name	Time	Method
Clinical Response (Complete and Partial)	assessed after 2 cycles, up to 2 years	Response to treatment was assessed after two cycles, according to International Working Group (IWG) criteria.

Secondary Outcome Measures

Name	Time	Method
Clinical Activity as Measured by Change in Peripheral Blood Counts and Changes in Transfusion Requirements	Baseline and after two cycles	ANC count at baseline and after two cycles were measured and compared. Due to the limited number of clinical responders, the changes in transfusion requirements were not measured.
Biological Activity as Measured by in Vivo Induction of Terminal Differentiation of Myeloid Progenitors and in Vivo Changes in Detectable Chromosomal Abnormalities	Baseline and 6, 12, 24, and 36 weeks

Trial Locations

Locations (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States