Brief Title
GTI-2040 and High-Dose Cytarabine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia
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)
Brief Summary
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.
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum-tolerated dose (MTD) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Secondary Outcome
Therapeutic response
Condition
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Intervention
GTI-2040
Study Arms / Comparison Groups
Stratum I (GTI-2040, cytarabine)
Description: 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.
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
Biological
Estimated Enrollment
51
Start Date
September 2003
Primary Completion Date
February 2009
Eligibility 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Guido Marcucci, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00070551
Organization ID
NCI-2012-01443
Secondary IDs
0304
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Guido Marcucci, Principal Investigator, Ohio State University
Verification Date
June 2013