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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00425477
• Other study ID #: J0675 CDR0000525989
• Secondary ID: P30CA006973JHOC-
• Status: Completed
• Phase: Phase 2
• Start date: November 2006
• Est. completion date: September 30, 2016

Study information

• Verified date: September 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: September 30, 2016
• Est. primary completion date: September 30, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Diseases
• Myeloproliferative Disorders
• Preleukemia
• Syndrome

Intervention

Biological:
• sargramostim

Drug:
• bexarotene

Genetic:
• cytogenetic analysis

• fluorescence in situ hybridization

Other:
• flow cytometry

• laboratory biomarker analysis

Procedure:
• biopsy

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Response (Complete and Partial)	Response to treatment was assessed after two cycles, according to International Working Group (IWG) criteria.	assessed after 2 cycles, up to 2 years
Secondary	Clinical Activity as Measured by Change in Peripheral Blood Counts and Changes in Transfusion Requirements	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
Secondary	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