Clofarabine, Cytarabine, and Idarubicin in Treating Patients With Intermediate-Risk or High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplasia

NCT00838240 | Unknown Phase 1 DMC

• 4 other identifiers: EORTC-06061EU-209052006-004912-28GIMEMA-AML-14A
• Study Type: interventional
• Target: 114
• Locations: 5 countries
• Sites: 10

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as clofarabine, cytarabine, and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of clofarabine and to see how well it works when given together with cytarabine and idarubicin in treating patients with intermediate-risk or high-risk acute myeloid leukemia or high-risk myelodysplasia.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

adult acute minimally differentiated myeloid leukemia (M0); adult acute myeloblastic leukemia without maturation (M1); adult acute myeloblastic leukemia with maturation (M2); adult acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); adult acute megakaryoblastic leukemia (M7); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with inv(16)(p13;q22); untreated adult acute myeloid leukemia; de novo myelodysplastic syndromes; secondary acute myeloid leukemia

Outcome Measures

Primary Outcomes (2)

• Toxicity as assessed by CTCAE v3.0 (Phase I)

• Response rate (Phase II)

Secondary Outcomes (6)

• Toxicity as assessed by CTCAE v3.0 (Phase II)

• Response rate (Phase I)

• Duration of survival

• Duration of survival from complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate

• Disease-free survival from CR/CRi

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive idarubicin IV over 5 minutes on days 1, 3, and 5, cytarabine IV continuously on days 1-10, and clofarabine IV over 1 hour on days 2, 4, 6, 8, and 10.

Drug: clofarabine; Drug: cytarabine; Drug: idarubicin

Arm II

EXPERIMENTAL

Patients receive idarubicin IV and cytarabine IV as in arm I. Patients also receive clofarabine IV by push injection over 10 minutes on days 2, 4, 6, 8, and 10.

Drug: clofarabine; Drug: cytarabine; Drug: idarubicin

Interventions

clofarabine DRUG

Given IV

Arm I; Arm II

cytarabine DRUG

Given IV

Arm I; Arm II

idarubicin DRUG

Given IV

Arm I; Arm II

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following by WHO criteria: * Acute myeloid leukemia (AML) (≥ 20% bone marrow blasts by bone marrow aspiration or biopsy) * No acute promyelocytic leukemia (M3) * All cytogenetic groups allowed, except for the following: * t(15;17) * t(8;21) or inv(16) AND a WBC count at diagnosis of \< 100,000/μL * Primary or secondary AML allowed, including AML after myelodysplasia (MDS) * High-risk MDS (≥ 10% bone marrow blasts by bone marrow aspiration or biopsy) * No chronic myelogenous leukemia in blast crisis or AML supervening a myeloproliferative disorder * Previously untreated disease, except for ≤ 14 days of hydroxyurea * No CNS leukemia PATIENT CHARACTERISTICS: * WHO performance status 0-2 * Serum creatinine ≤ 1.0 mg/dL or glomerular filtration rate \> 60 mL/min * AST/ALT ≤ 2.5 times upper limit of normal (ULN) * ALP ≤ 2.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception during and for ≥ 3 months after completion of study treatment * No active uncontrolled infection * No HIV positivity * No psychological, familial, sociological, or geographical conditions precluding compliance with study treatment or follow up * No concurrent severe uncontrolled cardiovascular disease (i.e., symptomatic congestive heart failure or symptomatic ischemic heart disease \[NYHA class III-IV\]) * No concurrent malignant disease PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No concurrent cytotoxic drugs or experimental therapies (e.g., antiangiogenic drugs, tyrosine kinase inhibitors)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Gruppo Italiano Malattie EMatologiche dell'Adulto: collaborator

Study Sites (10)

A.Z. Sint-Jan

Bruges, Belgium

RECRUITING

Institut Jules Bordet

Brussels, Belgium

NOT YET RECRUITING

CHU Sart-Tilman

Liège, Belgium

NOT YET RECRUITING

University Hospital Rebro

Zagreb, Croatia

NOT YET RECRUITING

Hôpital Saint Antoine AP-HP

Paris, France

NOT YET RECRUITING

Azienda Ospedallera Universitaria - Policlinico Tor Vergata

Roma, Italy

RECRUITING

Univesita Degli Studi "La Sapienza"

Roma, Italy

RECRUITING

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, Netherlands

RECRUITING

Leiden University Medical Center

Leiden, Netherlands

ACTIVE NOT RECRUITING

Radboud University Nijmegen Medical Center

Nijmegen, Netherlands

RECRUITING

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Monocytic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute; Congenital Abnormalities

Interventions

Clofarabine; Cytarabine; Idarubicin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

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; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Roel Willemze

  EORTC (Phase I) - Leiden University Medical Center, NL

  PRINCIPAL INVESTIGATOR

• Dominik Selleslag

  EORTC (Phase II) - AZ Sint-Jan, BE

  PRINCIPAL INVESTIGATOR

• Giovanna Meloni

  GIMEMA (Phase I & II) - Universita Degli Studi "La Sapienza", IT

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hilde Breyssens

CONTACT

hilde.breyssens@eortc.be

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2009
• First Posted: February 6, 2009
• Study Start: November 1, 2008
• Primary Completion: December 1, 2012
• Last Updated: July 20, 2012

Record last verified: 2012-07

Locations

BE (3); IT (2); NL (3); FR (1); CR (1)