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

Phase I Study of Farnesyl Transferase Inhibitor BMS-214662 (NSC 710086) in Acute Leukemias, Myelodysplastic Syndromes (RAEB and RAEB-T) and Chronic Myeloid Leukemia in Blast Phase

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

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (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.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: BMS-214662; Given IV; Other Names: farnesyltransferase inhibitor BMS-214662; FTI BMS 214662

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: April 1, 2000
• Primary Completion (Actual): October 1, 2002

Study Registration Dates

• First Submitted: September 11, 2000
• First Submitted That Met QC Criteria: December 23, 2003
• First Posted (Estimate): December 24, 2003

Study Record Updates

• Last Update Posted (Estimate): January 23, 2013
• Last Update Submitted That Met QC Criteria: January 22, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Disease; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Neoplastic Processes; Precancerous Conditions; Cell Transformation, Neoplastic; Carcinogenesis; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Recurrence; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Anemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; Leukemia, Promyelocytic, Acute; Anemia, Refractory, with Excess of Blasts; Anemia, Refractory
• Other Study ID Numbers: NCI-2012-02338; U01CA062461 (U.S. NIH Grant/Contract); DM99-290; CDR0000067887 (Registry Identifier: PDQ (Physician Data Query))