Clofarabine, Cytarabine, and Idarubicin in Treating Patients With Intermediate-Risk or High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplasia (AML-14A)

This study is currently recruiting participants.
Verified July 2012 by European Organisation for Research and Treatment of Cancer - EORTC
Sponsor:
Collaborator:
Gruppo Italiano Malattie EMatologiche dell'Adulto
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00838240
First received: February 5, 2009
Last updated: July 19, 2012
Last verified: July 2012

February 5, 2009
July 19, 2012
November 2008
December 2012   (final data collection date for primary outcome measure)
  • Toxicity as assessed by CTCAE v3.0 (Phase I) [ Designated as safety issue: Yes ]
  • Response rate (Phase II) [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00838240 on ClinicalTrials.gov Archive Site
  • Toxicity as assessed by CTCAE v3.0 (Phase II) [ Designated as safety issue: Yes ]
  • Response rate (Phase I) [ Designated as safety issue: No ]
  • Duration of survival [ Designated as safety issue: No ]
  • Duration of survival from complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate [ Designated as safety issue: No ]
  • Disease-free survival from CR/CRi [ Designated as safety issue: No ]
  • Incidence of relapse and incidence of death in CR/CRi [ Designated as safety issue: No ]
  • Toxicity as assessed by CTCAE v3.0 (Phase II) [ Designated as safety issue: Yes ]
  • Response rate (Phase II) [ Designated as safety issue: No ]
  • Duration of survival [ Designated as safety issue: No ]
  • Duration of survival from complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate [ Designated as safety issue: No ]
  • Disease-free survival from CR/CRi [ Designated as safety issue: No ]
  • Incidence of relapse and incidence of death in CR/CRi [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Clofarabine, Cytarabine, and Idarubicin in Treating Patients With Intermediate-Risk or High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplasia
Clofarabine in Combination With a Standard Remission Induction Regimen (AraC and Idarubicin) in Patients 18-60 Years Old With Previously Untreated Intermediate and Bad Risk Acute Myelogenous Leukemia (AML) or High Risk Myelodysplasia (MDS) : a Phase I-II Study of the EORTC-LG and GIMEMA (AML-14A Trial)

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.

OBJECTIVES:

Primary

  • To determine the optimum dose of clofarabine in combination with cytarabine and idarubicin in patients with previously untreated intermediate- and high-risk acute myeloid leukemia or high-risk myelodysplasia. (Phase I)
  • To determine the safety and tolerance of this regimen in order to determine the recommended phase II dose. (Phase I)
  • To explore the antitumor activity of this regimen in these patients. (Phase II)
  • To determine the activity expressed as complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate following induction therapy. (Phase II)

Secondary

  • To determine the activity expressed as CR/CRi rate following induction (1 or 2 courses) and consolidation therapy. (Phase I)
  • To determine hematopoietic recovery (platelets and neutrophils) after induction and consolidation therapy.
  • To determine safety and tolerability of this regimen. (Phase II)
  • To determine activity expressed as CR/CRi rate after consolidation therapy. (Phase II)
  • To determine feasibility of blood CD34 harvesting after consolidation therapy. (Phase II)
  • To determine disease-free and overall survival from CR/CRi. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of clofarabine followed by an randomized phase II study. Patients are stratified according to center, and presence of poor prognostic features (WBC at diagnosis ≥ 100,000/μL vs presence of very high risk cytogenetic features -5/5q-, -7/7q-, presence of complex abnormalities [> 3 abnormalities], 3q, t[6;9], or t[9;22]). Patients are randomized to 1 of 2 treatment arms.

  • Induction therapy:

    • Arm I: 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.
    • Arm II: 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.
  • Consolidation therapy: Patients receive cytarabine IV over 2 hours every 12 hours on days 1-6 and idarubicin IV over 5 minutes once daily on days 4-6.

After completion of study therapy, patients are followed periodically for 12 months.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Leukemia
  • Myelodysplastic Syndromes
  • Drug: clofarabine
    Given IV
  • Drug: cytarabine
    Given IV
  • Drug: idarubicin
    Given IV
  • Experimental: Arm I
    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.
    Interventions:
    • Drug: clofarabine
    • Drug: cytarabine
    • Drug: idarubicin
  • Experimental: Arm II
    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.
    Interventions:
    • Drug: clofarabine
    • Drug: cytarabine
    • Drug: idarubicin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
114
Not Provided
December 2012   (final data collection date for primary outcome measure)

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)
Both
18 Years to 60 Years
No
Contact: Hilde Breyssens hilde.breyssens@eortc.be
Belgium,   Croatia,   France,   Italy,   Netherlands
 
NCT00838240
EORTC-06061, EORTC-06061, EU-20905, 2006-004912-28, GIMEMA-AML-14A
Yes
European Organisation for Research and Treatment of Cancer - EORTC
European Organisation for Research and Treatment of Cancer - EORTC
Gruppo Italiano Malattie EMatologiche dell'Adulto
Principal Investigator: 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
European Organisation for Research and Treatment of Cancer - EORTC
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP