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

Chronic Myelomonocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00087204
• Other study ID #: NCI-2012-02609
• Secondary ID: MDA-2003-0909U01
• Status: Completed
• Phase: Phase 1
• First received: July 8, 2004
• Last updated: January 22, 2013
• Start date: May 2004

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

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• 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)
• Anemia
• Anemia, Refractory, with Excess of Blasts
• Blast Crisis
• Blastic Phase Chronic Myelogenous Leukemia
• Chronic Myelomonocytic Leukemia
• de Novo Myelodysplastic Syndromes
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Myelodysplastic Syndromes
• Neoplasm Metastasis
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• 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
• Syndrome

Intervention

Drug:
• becatecarin
Given IV

Other:
• 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	Maximum tolerated dose of becatecarin	Graded using the NCI CTCAE version 3.0.	21 days	Yes
Secondary	Survival		From date of first study drug administration to the date of death of the patients, assessed up to 3 years	No
Secondary	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	No
Secondary	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	No
Secondary	Duration of response		From the date of first objective response to the date of progression, assessed up to 3 years	No
Secondary	Time to response		From the date of first study drug administration until the first objective documentation of response, assessed up to 3 years	No