Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	OSU-0304 OSU-20030030, NCI-6108, NCT00070551, 6108

Objectives

Primary

1. 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

1. Determine the therapeutic response in patients treated with this regimen.
2. Determine the pharmacokinetics of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy (except hydroxyurea) (6 weeks for nitrosoureas or mitomycin)
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy except steroids for adrenal failure and hormones for non-disease-related conditions (e.g., insulin for diabetes)

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No concurrent palliative radiotherapy

Surgery

• Not specified

Other

• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 4 weeks

Hematopoietic

• Not specified

Hepatic

• 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*

 [Note: *Unless directly attributable to the malignancy]

Renal

• Creatinine no greater than 1.5 mg/dL*

 [Note: *Unless directly attributable to the malignancy]

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Resting ejection fraction at least 50%*

 [Note: *Unless directly attributable to the malignancy]

Other

• 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

Expected Enrollment

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

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.

Klisovic RB, Blum W, Wei X, et al.: Phase I study of GTI-2040, an antisense to ribonucleotide reductase, in combination with high-dose cytarabine in patients with acute myeloid leukemia. Clin Cancer Res 14 (12): 3889-95, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Guido Marcucci, MD, Protocol chair		Ph: 614-293-9868

Registry Information
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)
Trial Start Date		2003-10-02
Trial Completion Date		2009-02-23
Registered in ClinicalTrials.gov		NCT00070551
Date Submitted to PDQ		2003-09-08
Information Last Verified		2007-04-05
NCI Grant/Contract Number		CA76576, CA16058

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