GTI-2040 and High-Dose Cytarabine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00070551
First received: October 3, 2003
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

This phase I trial is studying the side effects and best dose of GTI-2040 and high-dose cytarabine in treating patients with refractory or relapsed acute myeloid leukemia. GTI-2040 may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy, such as cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Giving GTI-2040 together with cytarabine may kill more cancer cells.


Condition Intervention Phase
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)
Recurrent Adult Acute Myeloid Leukemia
Biological: GTI-2040
Drug: cytarabine
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of GTI2040 (NSC 722929; IND 67368) in Combination With High-dose Cytarabine in Refractory or Relapsed Acute Myeloid Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum-tolerated dose (MTD) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to day 42 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Therapeutic response [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Standard paired statistical tests, parametric and nonparametric, will be used to baseline with treatment values. With data collected serially over time, repeated measures analysis of variance will be used to analyze data.

  • Change in R2 expression in circulating and marrow leukemia cells [ Time Frame: From baseline to up to 6 years ] [ Designated as safety issue: No ]
    Standard paired statistical tests, parametric and nonparametric, will be used to baseline with treatment values. With data collected serially over time, repeated measures analysis of variance will be used to analyze data.


Enrollment: 51
Study Start Date: September 2003
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stratum I (GTI-2040, cytarabine)
Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 2 hours twice daily on days 2, 4, and 6.
Biological: GTI-2040
Given IV
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Other: pharmacological study
Optional correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Optional correlative studies
Experimental: Stratum II (GTI-2040, cytarabine)
Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 4 hours once daily on days 2-6. In both strata, treatment continues in the absence of unacceptable toxicity.
Biological: GTI-2040
Given IV
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Other: pharmacological study
Optional correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Optional correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and recommended phase II dose of GTI-2040 and high-dose cytarabine in patients with relapsed or refractory acute myeloid leukemia.

SECONDARY OBJECTIVES:

I. Determine the therapeutic response in patients treated with this regimen. II. Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation study. Patients are stratified according to age (under age 60 vs age 60 and over). Patients are assigned to 1 of 2 strata.

Stratum I (under age 60): Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 2 hours twice daily on days 2, 4, and 6.

Stratum II (age 60 and over): Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 4 hours once daily on days 2-6.

In both strata, treatment continues in the absence of unacceptable toxicity.

Cohorts of 3-6 patients per stratum receive escalating doses of GTI-2040 and high-dose cytarabine 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.

PROJECTED ACCRUAL: A total of 6-51patients will be accrued for this study within 2-16 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed acute myeloid leukemia according to the WHO classification
  • Relapsed or refractory disease, meeting 1 of the following criteria:

    • Unresponsive to initial treatment
    • Recurrent disease after treatment with prior conventional or high-dose chemotherapy with or without stem cell support
  • CNS involvement allowed provided there are no residual leukemic cells detected in the cerebrospinal fluid after intrathecal or radiation chemotherapy
  • Performance status - ECOG 0-2
  • At least 4 weeks
  • Bilirubin no greater than 2 times upper limit of normal* (ULN) (unless due to Gilbert's syndrome)
  • AST and ALT no greater than 3 times ULN*
  • Creatinine no greater than 1.5 mg/dL*
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Resting ejection fraction at least 50%*
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior allergy to study medications
  • No ongoing or active infection requiring IV antibiotics
  • No other concurrent uncontrolled illness
  • No serious medical or psychiatric illness that would preclude giving informed consent
  • More than 4 weeks since prior chemotherapy (except hydroxyurea) (6 weeks for nitrosoureas or mitomycin)
  • No other concurrent chemotherapy
  • No concurrent hormonal therapy except steroids for adrenal failure and hormones for non-disease-related conditions (e.g., insulin for diabetes)
  • More than 4 weeks since prior radiotherapy
  • No concurrent palliative radiotherapy
  • Prior therapy with antisense oligonucleotides allowed provided no toxic effects were experienced that were directly attributable to the antisense agents
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  • No concurrent chronic systemic anticoagulant therapy for medical conditions (e.g., prior deep vein thrombosis or atrial fibrillation)

    • Concurrent heparin to maintain central line patency (i.e., catheter flush) is allowed
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070551

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Principal Investigator: Guido Marcucci Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00070551     History of Changes
Other Study ID Numbers: NCI-2012-01443, 0304, CDR0000334898, OSU-20030030, NCI-6108, OSU-0304, U01CA076576
Study First Received: October 3, 2003
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Cytarabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014