Clofarabine Combinations in Relapsed/Refractory Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS) and Myeloid Blast Phase Chronic Myeloid Leukemia (CML)

NCT00067028 | Completed Phase 2 Results

• 1 other identifier: ID03-0181
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

The goal is to compare the drug combinations clofarabine/idarubicin/ara-C, clofarabine/ara-C, and clofarabine/idarubicin in the treatment of patients with Acute Myeloid Leukemia, high-grade MDS, or myeloid blast phase of Chronic Myeloid Leukemia who have relapsed following their initial therapy.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome; Chronic Myeloid Leukemia

Keywords

Chronic Myeloid Leukemia; CML Myeloid Blast Phase; Acute Myeloid Leukemia; Myelodysplastic Syndrome; Clofarabine; Clofarex; Clolar; Ara-C; Cytarabine; Cytosar; DepoCyt; Cytosine arabinosine hydrochloride; Idarubicin; Idamycin

Outcome Measures

Primary Outcomes (1)

• Participants With a Response

  Response assessed by blood test or bone marrow aspirate following day 21 of induction and then every 2 weeks thereafter until remission or non-response. Complete remission (CR): Disappearance all clinical and/or radiologic evidence of disease; Neutrophil count \> 1.0 x10\^9/L and platelet count \>100x10\^9/L, and normal bone marrow differential (\< 5% blasts). Complete remission without platelet recovery (CRp): Peripheral blood and bone marrow results as for CR, but with platelet counts of \> 20 x 10\^9/L and \< 100 x 10\^9/L. Partial remission (PR): Peripheral blood count recovery as for CR, but with decrease in marrow blasts of \> 50% and not more than 6-25% abnormal cells in the marrow. All other responses considered as failures.

  Up to 6 years

Secondary Outcomes (1)

• Overall Response Rate (ORR)

  Up to 6 years

Study Arms (3)

Clofarabine + Ara-C

EXPERIMENTAL

Clofarabine 40 mg/m\^2 by vein over 1 hour daily for 5 days. Ara-C Starting dose: 1 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.

Drug: Clofarabine 40mg/m^2; Drug: Ara-C 1 g/m^2

Clofarabine + Idarubicin

EXPERIMENTAL

Clofarabine 22.5 mg/m\^2 by vein over 1 hour daily for 5 days. Idarubicin 10 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.

Drug: Idarubicin 10mg/m^2; Drug: Clofarabine 22.5mg/m^2

Clofarabine + Idarubicin + Ara-C

EXPERIMENTAL

Clofarabine 22.5 mg/m\^2 by vein over 1 hour daily for 5 days. Idarubicin 6 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle. Ara-C Starting dose: 0.75 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.

Drug: Ara-C 0.75 g/m^2; Drug: Clofarabine 22.5mg/m^2; Drug: Idarubicin 6 mg/m^2

Interventions

Clofarabine 40mg/m^2 DRUG

40 mg/m\^2 by vein over 1 hour daily for 5 days.

Also known as: Clofarex, Clolar

Clofarabine + Ara-C

Idarubicin 10mg/m^2 DRUG

10 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle. Clofarabine + Idarubicin plus Ara-C: 6 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.

Also known as: Idamycin®,, Idamycin PFS®

Clofarabine + Idarubicin

Ara-C 0.75 g/m^2 DRUG

0.75 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.

Also known as: Cytosar-U®, Cytarabine, Cytosar, DepoCyt, Cytosine arabinosine hydrochloride

Clofarabine + Idarubicin + Ara-C

Clofarabine 22.5mg/m^2 DRUG

22.5 mg/m\^2 by vein over 1 hour daily for 5 days.

Also known as: Clofarex, Clolar

Clofarabine + Idarubicin; Clofarabine + Idarubicin + Ara-C

Ara-C 1 g/m^2 DRUG

1 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.

Also known as: Cytosar-U®, Cytarabine, Cytosar, DepoCyt, Cytosine arabinosine hydrochloride

Clofarabine + Ara-C

Idarubicin 6 mg/m^2 DRUG

6 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.

Also known as: Idamycin®,, Idamycin PFS®

Clofarabine + Idarubicin + Ara-C

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age \>/= 18 years and \< 60 years.
• Must be in first relapse of AML, or must receive treatment as first salvage in primary refractory AML; or have high-risk MDS (\>/= 10% blasts) with not more than one prior regimen of chemotherapy (therapy with hematopoietic growth factors, biological or targeted therapies are not counted). Patients in CML myeloid blast phase may receive clofarabine as frontline therapy or in first salvage.
• Total bilirubin \</= 2mg/dL, Serum glutamic pyruvic transaminase (SGPT) \</= 4 upper limit of normal (ULN), creatinine \</= 2.0mg/dL.
• Eastern Cooperative Oncology Group (ECOG) performance status \</= 2.
• Signed informed consent.
• Male and female patients who are fertile agree to use an effective barrier method of birth control (ie, latex condom, diaphragm, cervical cap, etc) to avoid pregnancy. Female patients need a negative serum or urine pregnancy test within 7 days of study enrollment (applies only if patient is of childbearing potential. Non-childbearing is defined as \>= 1 year postmenopausal or surgically sterilized).

You may not qualify if:

• Previous treatment with clofarabine.
• Active, uncontrolled, systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment, or any severe, concurrent disease, which, in the judgment of the investigator and after discussion with the Principal Investigator, would make the patient inappropriate for study entry.
• Symptomatic central nervous system (CNS) involvement.
• Patients who receive other chemotherapy. Patients must have been off previous therapy of \>/= 2 weeks and must have recovered from acute toxicity of all previous therapy prior to enrollment. Treatment may start earlier following discussion with the Principal Investigator.
• Cardiac ejection fraction \</= 30%.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Clofarabine; Idarubicin; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Hagop M Kantarjian,MD/Chair, Leukemia
• Organization: The University of Texas M. D. Anderson Cancer Center

hkantarjian@mdanderson.org

(713) 792-7026

Study Officials

• Stefan H Faderl, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2003
• First Posted: August 13, 2003
• Study Start: December 1, 2003
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: December 8, 2020
• Results First Posted: December 8, 2020

Record last verified: 2020-12

Locations

US (1)