Clofarabine and Ara-C for the Treatment of Relapsed AML and Untreated MDS

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Baylor Research Institute
ClinicalTrials.gov Identifier:
NCT00334074
First received: June 2, 2006
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

The purpose of this trial is to to determine the safety and effectiveness of therapeutic combination - Clofarabine and Cytarabine for the treatment of AML and MDS.


Condition Intervention Phase
Acute Myelogenous Leukemia
Myelodysplastic Syndromes
Chronic Myelogenous Leukemia
Drug: Clofarabine and Cytarabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Clofarabine and Cytarabine in Relapsed Standard-Risk AML and Untreated High-Risk MDS in Adult Patients, and Untreated AML in Selected Elderly Patients at High Risk of Anthracycline Toxicity

Resource links provided by NLM:


Further study details as provided by Baylor Research Institute:

Primary Outcome Measures:
  • Response Rate (Complete Response [CR] Plus Partial Response [PR]) of Clofarabine Plus Cytarabine in Patients With Relapsed/Refractory AML, Untreated MDS, CML in Blast Phase, or in Selected Untreated Patients With High Risk of Anthracycline Toxicity [ Time Frame: Proportion of confirmed responses was estimated by the number of patients who achieved a CR or PR, defined as two consecutive evaluations at least 4 weeks apart, divided by the number of eligible participants in the study. ] [ Designated as safety issue: No ]

    Based on International working group for diagnosis, standardization of response criteria, and treatment outcomes for reporting standards for therapeutic trials in Acute myeloid Leukemia:

    Complete Response (CR) was defined as normalization of marrow blasts (< 5%), recovery of normal heamtopoiesis (absolute neutrophil count >1 X 10^9/l, platelet count ≥100 X10^9/l, and absence of peripheral blood blasts, independent of transfusions and growth factor support.

    Partial response was defined as blood count recovery as for complete response with the exception of leukemic marrow blasts in the range of 6%-25% or a ≥50% decrease in bone marrow blasts.

    Treatment failure was defined as a <25% change in marrow blasts within 30 days of starting therapy



Secondary Outcome Measures:
  • Number of Participants Who Had an Adverse Event While on Treatment With Clofarabine Plus Cytarabine [ Time Frame: Up to five months (includes follow up period of 30 days) from the day patient received their first dose of study drug ] [ Designated as safety issue: Yes ]
    Patients will be monitored clinically and diagnostically using measures including blood test, bone marrow aspiration and MUGA. Toxicity assessment every week using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be performed.


Enrollment: 30
Study Start Date: August 2005
Study Completion Date: February 2008
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clofarabine and Cytarabine
Five consecutive days of clofarabine 40 mg/m^2 IVI over 1 hour followed 4 hours later by cytarabine 1000 mg/m^2 IVI over 2 hours
Drug: Clofarabine and Cytarabine
Phase II Trial of Clofarabine and Cytarabine in Relapsed Standard-Risk AML and Untreated High-Risk MDS in Adult Patients, and Untreated AML in selected Elderly Patients at high risk of anthracycline toxicity
Other Names:
  • Clofarabine: CAFdA; Cl-F-ara-A
  • Cytarabine: Ara-C

Detailed Description:

Previous studies of Clofarabine and Cytarabine combination treatment in adult AML and MDS patients showed promising results.

This study is done to confirm the findings from previous studies. Primary objective is to determine the overall response rate (complete response [CR] plus partial response [PR]); secondary objective of this study is to characterize and quantify the toxicity profile associated with clofarabine plus cytarabine treatment.

A maximum of 35 patients will be treated on this study. They will receive 5 consecutive days of clofarabine intra venous infusion (IVI) followed 4 hours later by cytarabine IVI.Patients will receive up to a maximum of 4 cycles of study treatment. Next cycle will start approximately 4 weeks after Day 1 of previous cycle.No other investigational or commercial agents including chemotherapy, radiotherapy, or immunotherapy may be administered to patients enrolled in this study with the intention of treating the underlying malignancy

Patients will remain on study, and be monitored until 4 months have elapsed from the beginning date of their last cycle of treatment.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Adult patients who are at least 18 years old with histologically confirmed disease as follows:

  • Standard or poor cytogenetic risk acute myelogenous leukemia (AML) according to the Southwestern Oncology Group (SWOG) criteria in first relapse or primary refractory status
  • Untreated high-risk myelodysplastic syndrome (MDS) defined as >10% blasts
  • Chronic myelogenous leukemia (CML) in accelerated phase or blast crisis failing imatinib therapy.
  • Selected elderly patients with untreated AML who are at high risk of anthracycline toxicity.

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
  • Laboratory values obtained less than or equal to 7 days prior to receiving study treatment:

    • Total bilirubin < 2.0 mg/dL unless elevated due to hemolysis
    • Aspartate transaminase (AST)/alanine transaminase (ALT) less than or equal to 5 × upper limit of normal (ULN)
    • Serum creatinine < 2.0 mg/dL
  • Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
  • Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
  • Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Exclusion Criteria:

  • Patients with FAB M3 unless relapsed after treatment with ATRA and arsenic trioxide.
  • Patients eligible to receive curative allogeneic transplant as determined by performance status, organ function, availability of a matched donor, etc.
  • Current concomitant chemotherapy, radiation therapy, or immunotherapy.
  • Use of investigational agents within 30 days or any anticancer therapy within 3 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy.
  • Active heart disease including myocardial infarction within the preceding 3 months.
  • History of severe coronary artery disease, arrhythmias other than atrial flutter or fibrillation requiring medication, or uncontrolled congestive heart failure
  • Dyspnea at rest or with minimal exertion.
  • Patients with an active, uncontrolled systemic infection considered to be opportunistic, life-threatening, or clinically significant at the time of treatment or with a known or suspected fungal infection (ie, patients on parenteral antifungal therapy).
  • Pregnant or lactating patients.
  • Prior enrollment in this trial.
  • Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00334074

Locations
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
Sponsors and Collaborators
Baylor Research Institute
Investigators
Principal Investigator: Edward Agura, MD Baylor University Medical Center - Director Blood and Marrow Transplantation Services
  More Information

No publications provided

Responsible Party: Baylor Research Institute
ClinicalTrials.gov Identifier: NCT00334074     History of Changes
Other Study ID Numbers: 004-145, 004-145
Study First Received: June 2, 2006
Results First Received: April 1, 2013
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor Research Institute:
AML
MDS
CML
Relapsed
Refractory
Chemo treatment
Clofarabine
Cytarabine
standard or poor cytogenetic risk AML
untreated high-risk (>10% blasts) MDS
CML in accelerated phase or blast crisis
Elderly AML patients with risk of anthracycline toxicity

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Leukemia, Myeloid, Acute
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Neoplasms by Histologic Type
Myeloproliferative Disorders
Cytarabine
Clofarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 01, 2014