BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Excess Blasts; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Previously Treated Myelodysplastic Syndromes; Relapsing Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Adult Acute Promyelocytic Leukemia (M3)

Treatments: Other: pharmacological study; Other: laboratory biomarker analysis; Drug: BMS-214662

Study type: Interventional

Funder types: NIH

Identifiers

NCT00006213

DM99-290

CDR0000067887 (Registry Identifier)

U01CA062461 (U.S. NIH Grant/Contract)

NCI-2012-02338

Details and patient eligibility

About

Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of BMS-214662 in treating patients who have acute leukemia, myelodysplastic syndrome, or chronic myeloid leukemia in blast phase

Full description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and dose limiting toxicity of BMS-214662 in patients with acute leukemia, myelodysplastic syndrome, or chronic myeloid leukemia in blast phase.

II. Determine any preliminary evidence of antileukemia activity of this drug in these patients.

OUTLINE: This is a dose escalation study.

Patients receive BMS-214662 IV over 1 hour weekly for 4 weeks. Treatment continues every 4 weeks for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of BMS-214662 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 10 months.

Enrollment: 30 patients

Sex: All

Ages: 15+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must have:

  • AML, ALL, or high-risk MDS (RAEB or RAEB-t) that has:

    • Not responded (no CR) to initial induction chemotherapy, or
    • Recurred after an initial CR of < 1 year, or
    • Recurred after an initial CR of > 1 year and failed to respond to an initial reinduction attempt, or
    • Recurred more than once, or

  • Chronic myeloid leukemia in myeloid blast phase

    • Patients with CML blast phase may receive BMS-214662 as their first therapy for blast phase or after failing other treatments for blast phase

  • Patients with refractory or relapsed acute promyelocytic leukemia are eligible provided they have failed an ATRA-containing regimen

• Performance status of =< 0-2

• Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of the hospital

• Patients must have been off chemotherapy for the 4 weeks prior to entering this study and recovered from the toxic effects of that therapy; patients with evidence of rapidly progressive disease (i.e., absolute peripheral blood blast count >= 5 x 10^9/L and increasing by >= 1 x 10^9/L/24 hours) may receive treatment before 4 weeks from the previous treatment providing they have recovered from all toxic effects of that therapy; use of hydroxyurea on patients with rapidly proliferative disease is allowed up to 24 hours prior to the start of therapy

• Bilirubin =< 1.5 mg/dL

• Creatinine =< 1.5 mg/dL or creatinine clearance >= 60 mL/hr

• Patients who are likely to benefit from allogeneic bone marrow transplantation (i.e., age < 60 years of physiological age with histocompatible donor) should be excluded from this study unless such therapy is not feasible

Exclusion criteria

• Pregnant and nursing females will be excluded; patients of childbearing potential should practice effective methods of contraception
• Patients with prolonged QTc interval on EKG are excluded

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Treatment (BMS-214662)

Experimental group

Description:

Patients receive BMS-214662 IV over 1 hour weekly for 4 weeks. Treatment continues every 4 weeks for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression.

Treatment:

Other: laboratory biomarker analysis

Drug: BMS-214662

Other: pharmacological study