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A Phase I Study of GTI2040 (NSC 722929; IND 67368) in Combination With High-dose Cytarabine in Refractory or Relapsed Acute Myeloid Leukemia (AML)


Phase 1
18 Years
N/A
Not Enrolling
Both
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

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Trial Information

A Phase I Study of GTI2040 (NSC 722929; IND 67368) in Combination With High-dose Cytarabine in Refractory or Relapsed Acute Myeloid Leukemia (AML)


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose (MTD) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Outcome Time Frame:

Up to day 42

Safety Issue:

Yes

Principal Investigator

Guido Marcucci

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01443

NCT ID:

NCT00070551

Start Date:

September 2003

Completion Date:

Related Keywords:

  • 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
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

Ohio State University Medical CenterColumbus, Ohio  43210