GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia

NCT ID: NCT00459212

Last Updated: 2015-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Brief Summary

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This phase I trial is studying the side effects and best dose of GTI-2040 in treating patients with relapsed, refractory, or high-risk acute leukemia, high-grade myelodysplastic syndromes, or refractory or blastic phase chronic myelogenous leukemia. Drugs used in chemotherapy, such as GTI-2040, work in different ways to stop the growth of cancer or abnormal cells, either by killing the cells or by stopping them from dividing.

Detailed Description

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OBJECTIVES:

I. Determine the maximum tolerated dose of GTI-2040 in patients with relapsed, refractory, or high-risk acute leukemia, high-grade myelodysplastic syndromes, or refractory or blastic phase chronic myelogenous leukemia.

II. Assess the toxicity and efficacy of this drug in these patients. III. Assess plasma and intracellular pharmacokinetics of this drug in these patients.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive GTI-2040 IV continuously on days 1-4 and 15-18. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of GTI-2040 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 toxicity.

Blood samples are collected on days 1, 4, 15, and 19 of course 1 for pharmacokinetic studies. Samples are analyzed by proteomic assay, dCTP pool measurement, and real-time polymerase chain reaction for mRNA of RRM2, RRM1, and p53R2.

Conditions

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Acute Undifferentiated Leukemia 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 de Novo Myelodysplastic Syndromes Previously Treated Myelodysplastic Syndromes Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Relapsing Chronic Myelogenous Leukemia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Untreated Adult Acute Lymphoblastic Leukemia Untreated Adult Acute Myeloid Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I

Patients receive GTI-2040 IV continuously on days 1-4 and 15-18.

Group Type EXPERIMENTAL

GTI-2040

Intervention Type DRUG

Given IV

pharmacological study

Intervention Type PROCEDURE

Correlative study

laboratory biomarker analysis

Intervention Type PROCEDURE

Correlative study

Interventions

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GTI-2040

Given IV

Intervention Type DRUG

pharmacological study

Correlative study

Intervention Type PROCEDURE

laboratory biomarker analysis

Correlative study

Intervention Type PROCEDURE

Other Intervention Names

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pharmacological studies

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of 1 of the following:

* Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) refractory to primary standard induction therapy
* Relapsed or refractory acute leukemia
* Chronic myelogenous leukemia (CML) in blast crisis at diagnosis OR that failed prior aggressive induction chemotherapy
* Diagnosis of 1 of the following:

* Acute leukemia secondary to preexisting hematologic condition or prior chemotherapy at diagnosis OR that failed prior aggressive induction chemotherapy
* Advanced myelodysplastic syndromes (intermediate-1 or greater)
* De novo acute leukemia (myeloid or nonmyeloid)
* Not a candidate for aggressive standard induction chemotherapy
* De novo AML or ALL (patients \> 60 years of age)
* No suspected or proven active CNS leukemia
* ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100%
* Life expectancy \>= 8 weeks
* Bilirubin =\< 1.5 mg/dL
* AST and ALT \< 3 times upper limit of normal (ULN)
* Creatinine =\< 1.5 times ULN
* No HIV positivity
* Fertile patients must use effective contraception
* No history of allergic reactions attributed to other phosphorothiolated oligonucleotides
* No uncontrolled intercurrent illness including, but not limited to, any of the following:

* Ongoing, active, or poorly controlled infection
* Symptomatic congestive heart failure
* Unstable angina pectoris
* No uncontrolled intercurrent illness including, but not limited to, any of the following:

* Cardiac arrhythmia
* Poorly controlled pulmonary disease
* Psychiatric illness or social situation that would preclude study compliance
* Recovered from all prior therapies
* Prior autologous or allogeneic stem cell transplantation allowed (No active graft-vs-host disease \> grade 2)
* At least 2 weeks since prior and no concurrent cytotoxic chemotherapy
* At least 2 weeks since prior and no concurrent biologic therapy
* At least 2 weeks since any other prior investigational agent
* No other concurrent anticancer therapy, including radiotherapy or hormonal therapy
* Concurrent imatinib mesylate for CML allowed
* Not pregnant or nursing
* Negative pregancy test
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mark Kirschbaum

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

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City of Hope Medical Center

Duarte, California, United States

Site Status

Countries

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United States

Other Identifiers

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PHI-57

Identifier Type: -

Identifier Source: secondary_id

CDR0000539257

Identifier Type: -

Identifier Source: secondary_id

U01CA062505

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00206

Identifier Type: -

Identifier Source: org_study_id