Study of Clofarabine & Cytosine Arabinoside Therapy for Older Adults With Acute Myeloid Leukemia

NCT00081822 | Completed Phase 1 DMC

• 2 other identifiers: F040114019UAB 0341
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to determine the recommended phase II dose of clofarabine when administered in combination with standard dose Ara-C to older (\>=60 years of age) patients with newly diagnosed acute myeloid leukemia (AML).

Conditions

Acute Myeloid Leukemia

Keywords

Foran; clofarabine; cytosine arabinoside; acute myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Median time to complete response (CR)

  1 year

Secondary Outcomes (1)

• To evaluate quality of life parameters before, during and after therapy in the older adult (>60 years) population

  1 year

Study Arms (1)

Clofarabine + Ara-C

OTHER

An initial dose escalation of clofarabine with a fixed standard dose of Ara-C in phase I will be used to determine an optimal phase II dose.

Drug: clofarabine; Drug: Ara-C

Interventions

clofarabine DRUG

Clofarabine should be administered by daily intravenous infusion over 2 hours.Following demonstration of DLT at Dose Level -I (22.5 mg/m2/day days 2-6) and demonstration that Dose Level -II (15mg/m2day days 2-6) is the 'optimal phase II dose', an additional Dose Level -1½ (20mg/m2/day, days 2-6) will be added to explore an increased dose of clofarabine intermediate between Dose Levels -I and -II.

Also known as: CLOFAREX TM

Clofarabine + Ara-C

Ara-C DRUG

Ara-C: Administer Ara-C by continuous infusion of 100mg/m2/day on days 1 to 7 for cycle 1, and on days 1 to 5 for cycles 2 \& 3.

Also known as: Cytosine arabinoside, Cytarabine, Cytosar-U, Arabinosyl

Clofarabine + Ara-C

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have newly diagnosed AML (FAB classification types M0-M2 or M4-M7 or WHO classification) excluding acute promyelocytic leukemia (APL) or AML with any of the following chromosomal translocations: t(15;17)(q22;q21); t(11;17)(q23;q21); t(11;17)(q13;q21); t(5;17)(q32;q12)..
• Have greater than or equal to 20% blasts in the bone marrow.
• Have greater than or equal to 20% cellularity in the bone marrow.
• Provide written informed consent.
• Must be 60-75 years of age at diagnosis.
• Have an Karnofsky performance status of ≥60.
• Women of childbearing potential (\<1 year post-menopausal unless surgically sterilized) and sexually active males must have a negative urine pregnancy test, and agree to use an effective barrier method of birth control (i.e. latex condom, diaphragm, cervical cap, etc) to avoid pregnancy.
• Able to comply with study procedures and follow-up examinations.
• Have adequate organ function as indicated by the following laboratory values, obtained within 7 days prior to registration:

You may not qualify if:

• Patients with pre-existing myelodysplastic syndrome, or with antecedent hematologic disorder of \>3 months duration, will be excluded. Those with concomitant myelodysplasia/trilineage dysplasia noted at the time of diagnosis of AML will be eligible 74
• Have secondary AML (AML following chemotherapy or radiation therapy).
• Have an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment.
• Have a psychiatric disorder(s) that would interfere with consent, study participation or follow-up.
• Are receiving other chemotherapy or corticosteroids (unless the latter is administered at a low dose for pre-medication purposes or for the treatment of chronic conditions - e.g., rheumatoid arthritis).
• Have received prior treatment for leukemia. Patients who have received growth factors, cytokine support, leukapheresis, hydroxyurea, or cranial irradiation will be allowed but must discontinue treatment at least 24 hours prior to beginning treatment with clofarabine. If used, hydroxyurea must be discontinued 48 hours prior to the initiation of chemotherapy.
• Have any other severe concurrent disease (severe coronary artery disease (NYHA class \>II), significant neurological disorder, uncontrolled diabetes, etc.), which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• Have active central nervous system involvement with leukemia.
• Other malignancy within the past year, with the exception of basal cell or non-metastatic squamous cell carcinoma of the skin

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

The University of Nebraska

Omaha, Nebraska, 68198, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Clofarabine; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• James M Foran, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2004
• First Posted: April 23, 2004
• Study Start: January 1, 2004
• Primary Completion: April 1, 2009
• Study Completion: August 1, 2011
• Last Updated: April 20, 2012

Record last verified: 2012-04

Locations

US (3)