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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Refractory Anemia With Excess Blasts in Transformation; Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; de Novo Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Previously Treated Myelodysplastic Syndromes; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia

Treatments: Other: laboratory biomarker analysis; Drug: becatecarin

Study type: Interventional

Funder types: NIH

Identifiers

NCT00087204

CDR0000373813 (Registry Identifier)

NCI-2012-02609

MDA-2003-0909

U01CA062461 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

Treatment (becatecarin)

Experimental group

Description:

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.

Treatment:

Other: laboratory biomarker analysis

Drug: becatecarin