Clinical trial NCT00425477: Bexarotene and GM-CSF in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia
Official title: A Phase II Study of Bexarotene + Sargromastastin as Agents of Differentiation in MDS and AML
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Keywords: refractory anemia with excess blasts
recurrent adult acute myeloid leukemia
untreated adult acute myeloid leukemia
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
myelodysplastic/myeloproliferative disease, unclassifiable
refractory anemia with ringed sideroblasts
refractory cytopenia with multilineage dysplasia
chronic myelomonocytic leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult pure erythroid leukemia (M6b)
adult erythroleukemia (M6a)
adult acute megakaryoblastic leukemia (M7)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-01-23
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Clinical Response (Complete and Partial)
timeFrame: assessed after 2 cycles, up to 2 years
Secondary outcomes:
measure: Clinical Activity as Measured by Change in Peripheral Blood Counts and Changes in Transfusion Requirements
timeFrame: Baseline and after two cycles
measure: Biological Activity as Measured by in Vivo Induction of Terminal Differentiation of Myeloid Progenitors and in Vivo Changes in Detectable Chromosomal Abnormalities
timeFrame: Baseline and 6, 12, 24, and 36 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: B. Douglas Smith, MD
role: STUDY_CHAIR
References: