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

Phase 1

Completed

• Conditions: Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation
• Interventions: Drug: BMS-214662; Other: pharmacological study; Other: laboratory biomarker analysis

• Registration Number: NCT00006213
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

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

Detailed 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.

Study Timeline

• Study Start: 2000-04
• Study First Submitted: 2000-09-11
• Primary Completion: 2002-10
• Study First Submitted QC: 2003-12-23
• Study First Posted: 2003-12-24
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-22
• Last Update Posted: 2013-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (BMS-214662)	pharmacological 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.
Treatment (BMS-214662)	laboratory biomarker analysis	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 (BMS-214662)	BMS-214662	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.

Primary Outcome Measures

Name	Time	Method
MTD defined as the dose preceding that at which 2 of 6 patients experience DLT assessed using NCI CTC version 2.0	4 weeks	Non-parametric tests will be used to study the relationship between baseline and post-therapy values at different dose levels and times.

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States