3-AP and High-Dose Cytarabine in Treating Patients With Advanced Hematologic Malignancies

Brief Title

3-AP and High-Dose Cytarabine in Treating Patients With Advanced Hematologic Malignancies

Official Title

A Phase I Study of Triapine in Combination With High Dose Ara-C (Hi-DAC) in Patients With Advanced Hematologic Malignancies

Brief Summary

      Drugs used in chemotherapy, such as cytarabine, work in different ways to stop cancer cells
      from dividing so they stop growing or die. 3-AP may help cytarabine kill more cancer cells by
      making them more sensitive to the drug. This phase I trial is studying the side effects and
      best dose of 3-AP when given with high-dose cytarabine in treating patients with advanced
      hematologic malignancies
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. Determine the maximum tolerated dose of 3-AP (Triapine) administered with high-dose
      cytarabine in patients with advanced hematologic malignancies.

      SECONDARY OBJECTIVES:

      I. Determine the clinical activity of this regimen in these patients. II. Determine the
      effect of treatment with 3-AP (Triapine) on intracellular levels of cytarabine in these
      patients.

      OUTLINE: This is a dose-escalation study of 3-AP (Triapine).

      Patients receive high-dose cytarabine IV over 2 hours on days 1-5 and 3-AP (Triapine) IV over
      2 hours on days 2-5. Treatment repeats every 28 days for up to 4 courses in the absence of
      disease progression or unacceptable toxicity.

      Cohorts of 3-6 patients in each stratum receive escalating doses of 3-AP (Triapine) 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.

      Patients are followed for up to 2 years.

      PROJECTED ACCRUAL: A total of 6-48 patients (3-24 per stratum) will be accrued for this study
      within 15-24 months.
    

Study Phase

Phase 1

Study Type

Interventional

Primary Outcome

MTD defined as the dose preceding that at which greater than or equal to 2 patients experience dose-limiting toxicity assessed using NCI CTCAE version 3.0

Condition

Accelerated Phase Chronic Myelogenous Leukemia

Intervention

cytarabine

Study Arms / Comparison Groups

 Treatment (cytarabine and triapine)

Description:  Patients receive high-dose cytarabine IV over 2 hours on days 1-5 and triapine IV over 2 hours on days 2-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Publications

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

Recruitment Status

Drug

Estimated Enrollment

48

Start Date

January 2004

Primary Completion Date

July 2008

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of 1 of the following hematologic malignancies:

               -  Relapsed or refractory acute myeloid leukemia (AML)

               -  Relapsed or refractory acute lymphoblastic leukemia

               -  Secondary AML, including AML arising from antecedent hematologic diseases, such
                  as myelodysplastic syndromes or myeloproliferative disorders OR therapy-related
                  AML

               -  Chronic myeloid leukemia in accelerated or blast phase

          -  Refractory to standard therapy or no standard therapy exists

          -  No known brain metastases

          -  Performance status - CALGB 0-2

          -  Performance status - Karnofsky 60-100%

          -  No G6PD deficiency

          -  Bilirubin < 2.0 mg/dL (unless due to Gilbert's syndrome)

          -  AST and ALT < 2.5 times upper limit of normal (ULN)

          -  Creatinine < 1.5 times ULN

          -  No symptomatic congestive heart failure

          -  No unstable angina pectoris

          -  No cardiac arrhythmia

          -  No pulmonary disease requiring oxygen

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No prior allergic reactions attributed to compounds of similar chemical or biological
             composition to study drugs

          -  No neuropathy

          -  No ongoing or active infection

          -  No psychiatric illness or social situation that would preclude study compliance

          -  No other concurrent uncontrolled illness

          -  No concurrent biologic agents

          -  At least 72 hours since prior hydroxyurea

          -  At least 2 weeks since other prior chemotherapy (6 weeks for mitomycin or
             nitrosoureas)

          -  No other concurrent chemotherapy

          -  At least 2 weeks since prior radiotherapy

          -  No concurrent radiotherapy

          -  Recovered from all prior therapy

          -  At least 4 weeks since prior investigational agents

          -  No other concurrent investigational therapy

          -  No other concurrent anticancer therapy

          -  No concurrent combination antiretroviral therapy for HIV-positive patients
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Olatoyosi Odenike, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT00077181

Organization ID

NCI-2012-02570

Secondary IDs

UCCRC-12806B

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

Olatoyosi Odenike, Principal Investigator, University of Chicago Comprehensive Cancer Center

Verification Date

January 2013