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

Recurrent Adult Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006213
• Other study ID #: NCI-2012-02338
• Secondary ID: DM99-290U01CA062
• Status: Completed
• Phase: Phase 1
• First received: September 11, 2000
• Last updated: January 22, 2013
• Start date: April 2000

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. primary completion date: October 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Acute Promyelocytic Leukemia (M3)
• Anemia
• Anemia, Refractory, with Excess of Blasts
• Blast Crisis
• Blastic Phase Chronic Myelogenous Leukemia
• Childhood Myelodysplastic Syndromes
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Promyelocytic, Acute
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• 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
• Relapsing Chronic Myelogenous Leukemia
• Syndrome

Intervention

Drug:
• BMS-214662
Given IV

Other:
• pharmacological study
Correlative studies
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes