Rebeccamycin Analog in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00087204

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

This phase I trial is studying the side effects and best dose of rebeccamycin analog in treating patients with relapsed or refractory acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, or chronic myelogenous leukemia in blast phase. Drugs used in chemotherapy, such as rebeccamycin analog, work in different ways to stop cancer cells from dividing so they stop growing or die

Condition or Disease	Intervention/Treatment	Phase
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Blastic Phase Chronic Myelogenous Leukemia Chronic Myelomonocytic Leukemia de Novo Myelodysplastic Syndromes Previously Treated Myelodysplastic Syndromes Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Refractory Anemia With Excess Blasts Refractory Anemia With Excess Blasts in Transformation Relapsing Chronic Myelogenous Leukemia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes	Drug: becatecarin Other: laboratory biomarker analysis	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose and dose-limiting toxicity of rebeccamycin analogue (XL119) in patients with relapsed or refractory acute myeloid leukemia, myelodysplastic syndromes, acute lymphoblastic leukemia, or chronic myelogenous leukemia in blastic phase.

OUTLINE: This is a dose-escalation study.

Patients receive rebeccamycin analogue (XL119) IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 1 additional course beyond CR. Patients achieving a partial response (PR) or hematologic improvement (HI) receive 2 additional courses beyond PR or HI. Cohorts of 3-6 patients receive escalating doses of XL119 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study Of XL119 In Patients With Relapsed Or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndromes, Acute Lymphocytic Leukemia, Or Chronic Myeloid Leukemia In Blastic-Phase

Study Start Date :

May 1, 2004

Actual Primary Completion Date :

Jan 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (becatecarin) Patients receive rebeccamycin analogue (XL119) IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a CR receive 1 additional course beyond CR. Patients achieving a PR or HI receive 2 additional courses beyond PR or HI. Cohorts of 3-6 patients receive escalating doses of XL119 until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.	Drug: becatecarin Given IV Other Names: BMS-181176 rebeccamycin analogue rebeccamycin analogue, tartrate salt XL119 Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (becatecarin)

Patients receive rebeccamycin analogue (XL119) IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a CR receive 1 additional course beyond CR. Patients achieving a PR or HI receive 2 additional courses beyond PR or HI. Cohorts of 3-6 patients receive escalating doses of XL119 until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Drug: becatecarin

Given IV

Other Names:

BMS-181176

rebeccamycin analogue

rebeccamycin analogue, tartrate salt

XL119

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of becatecarin [21 days]
Graded using the NCI CTCAE version 3.0.

Secondary Outcome Measures

Survival [From date of first study drug administration to the date of death of the patients, assessed up to 3 years]
Time to progression [From the date of first study drug administration to the date that the patient is withdrawn because of clinical or radiographic progressive disease, or death from any cause, assessed up to 3 years]
Time to treatment failure [From the date of first study drug administration to the date of withdrawal from the study for any reason other than study closure, assessed up to 3 years]
Duration of response [From the date of first objective response to the date of progression, assessed up to 3 years]
Time to response [From the date of first study drug administration until the first objective documentation of response, assessed up to 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of 1 of the following:
Acute myeloid leukemia
Myelodysplastic syndromes, including 1 of the following:
Refractory anemia with excess blasts (RAEB)
RAEB in transformation
Chronic myelomonocytic leukemia in transformation with ≥ 10% peripheral blood or bone marrow blasts
Acute lymphoblastic leukemia
Chronic myelogenous leukemia in blastic phase
Relapsed or refractory disease, defined as 1 of the following:
Failed to achieve a complete response (CR) to a standard induction regimen
Relapsed after achieving a CR
Failed last cytotoxic regimen before study entry
No alternate, potentially curative option available
No known CNS disease
Performance status - ECOG 0-2
SGOT and SGPT normal
Bilirubin normal
Creatinine normal
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV-positive patients with normal CD4 count and without AIDS-defining disease allowed
No history of allergic reaction attributed to compounds of similar chemical or biologic composition to rebeccamycin analogue (XL119)
No concurrent uncontrolled illness
No active or ongoing infection
No psychiatric illness or social situation that would preclude study compliance
No prior allogeneic stem cell transplantation
No concurrent prophylactic hematopoietic colony-stimulating factors (CSF)
No epoetin alfa or hematopoietic CSF during course 1 of study therapy
More than 7 days since prior cytotoxic chemotherapy except for hydroxyurea
More than 7 days since prior radiotherapy
Recovered from all prior therapy
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent anticancer agents or therapies
No other concurrent antileukemic agents or therapies
No other concurrent investigational agents or therapies
No other concurrent cytotoxic agents