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

September 7, 2018 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

A Phase II Study of Bexarotene + Sargromastastin as Agents of Differentiation in MDS and AML

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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.
Other: laboratory biomarker analysis
Procedure: biopsy
Other: flow cytometry
Biological: sargramostim
Genetic: cytogenetic analysis
Genetic: fluorescence in situ hybridization
Drug: bexarotene

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Response (Complete and Partial)
Time Frame: assessed after 2 cycles, up to 2 years
Response to treatment was assessed after two cycles, according to International Working Group (IWG) criteria.
assessed after 2 cycles, up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Activity as Measured by Change in Peripheral Blood Counts and Changes in Transfusion Requirements
Time Frame: 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.
Baseline and after two cycles
Biological Activity as Measured by in Vivo Induction of Terminal Differentiation of Myeloid Progenitors and in Vivo Changes in Detectable Chromosomal Abnormalities
Time Frame: Baseline and 6, 12, 24, and 36 weeks
Baseline and 6, 12, 24, and 36 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 1, 2006

Primary Completion (ACTUAL)

September 30, 2016

Study Completion (ACTUAL)

September 30, 2016

Study Registration Dates

First Submitted

January 19, 2007

First Submitted That Met QC Criteria

January 19, 2007

First Posted (ESTIMATE)

January 23, 2007

Study Record Updates

Last Update Posted (ACTUAL)

October 5, 2018

Last Update Submitted That Met QC Criteria

September 7, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • J0675 CDR0000525989
  • P30CA006973 (U.S. NIH Grant/Contract)
  • JHOC-J0675
  • JHOC-NA_00003076

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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