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

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Brief Title

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

Official Title

Phase I and Pharmacodynamic Study of GTI-2040 (NSC 722929, IND 67368) in Acute Leukemias

Brief Summary

      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

      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.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)

Secondary Outcome

 Objective tumor response

Condition

Acute Undifferentiated Leukemia

Intervention

GTI-2040

Study Arms / Comparison Groups

 Arm I
Description:  Patients receive GTI-2040 IV continuously on days 1-4 and 15-18.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

24

Start Date

March 2007


Primary Completion Date

December 2010

Eligibility Criteria

        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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Mark Kirschbaum, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00459212

Organization ID

NCI-2009-00206

Secondary IDs

PHI-57

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Mark Kirschbaum, Principal Investigator, City of Hope Medical Center


Verification Date

April 2013