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

NCT ID: NCT00087204

Last Updated: 2013-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31

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

Detailed Description

OBJECTIVES:

I. 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

becatecarin

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

becatecarin

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

BMS-181176; rebeccamycin analogue; rebeccamycin analogue, tartrate salt; XL119

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francis Giles

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

MDA-2003-0909

Identifier Type: -

Identifier Source: secondary_id

U01CA062461

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000373813

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02609

Identifier Type: -

Identifier Source: org_study_id