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

NCT00425477 | Completed Phase 2 Results

• 4 other identifiers: J0675 CDR0000525989P30CA006973JHOC-J0675JHOC-NA_00003076
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

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)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Clinical Activity as Measured by Change in Peripheral Blood Counts and Changes in Transfusion Requirements

  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

  Baseline and 6, 12, 24, and 36 weeks

Study Arms (1)

Bexarotene + GM-CSF

EXPERIMENTAL

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.

Biological: sargramostim; Drug: bexarotene; Genetic: cytogenetic analysis; Genetic: fluorescence in situ hybridization; Other: flow cytometry; Other: laboratory biomarker analysis; Procedure: biopsy

Interventions

cytogenetic analysis GENETIC

Bexarotene + GM-CSF

sargramostim BIOLOGICAL

Bexarotene + GM-CSF

bexarotene DRUG

Bexarotene + GM-CSF

fluorescence in situ hybridization GENETIC

Bexarotene + GM-CSF

flow cytometry OTHER

Bexarotene + GM-CSF

laboratory biomarker analysis OTHER

Bexarotene + GM-CSF

biopsy PROCEDURE

Bexarotene + GM-CSF

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Anemia, Refractory, with Excess of Blasts; Leukemia, Myeloid, Acute; Myeloproliferative Disorders; Leukemia, Myelomonocytic, Chronic; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Monocytic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute

Interventions

sargramostim; Bexarotene; Cytogenetic Analysis; In Situ Hybridization, Fluorescence; Flow Cytometry; Biopsy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Anemia, Refractory; Anemia; Leukemia, Myeloid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Histological Techniques; Nucleic Acid Hybridization; Cell Separation; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Cytodiagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Results Point of Contact

• Title: B. Douglas Smith
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

smithdo@jhmi.edu

410-614-5068

Study Officials

• B. Douglas Smith, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2007
• First Posted: January 23, 2007
• Study Start: November 1, 2006
• Primary Completion: September 30, 2016
• Study Completion: September 30, 2016
• Last Updated: October 5, 2018
• Results First Posted: September 5, 2018

Record last verified: 2018-09

Locations

US (1)