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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by European Organisation for Research and Treatment of Cancer - EORTC.
Recruitment status was  Recruiting
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
  Purpose

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.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Drug: clofarabine
Drug: cytarabine
Drug: idarubicin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Toxicity as assessed by CTCAE v3.0 (Phase I) [ Designated as safety issue: Yes ]
  • Response rate (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 114
Study Start Date: November 2008
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: clofarabine
Given IV
Drug: cytarabine
Given IV
Drug: idarubicin
Given IV
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.
Drug: clofarabine
Given IV
Drug: cytarabine
Given IV
Drug: idarubicin
Given IV

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  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: NCT00838240

Contacts
Contact: Hilde Breyssens hilde.breyssens@eortc.be

Locations
Belgium
A.Z. Sint-Jan Recruiting
Brugge, Belgium
Principal Investigator: Dominik Selleslag         
Institut Jules Bordet Not yet recruiting
Brussel, Belgium
Principal Investigator: Dominique Bron         
CHU Sart-Tilman Not yet recruiting
Liège, Belgium
Principal Investigator: Frédéric Baron         
Croatia
University Hospital Rebro Not yet recruiting
Zagreb, Croatia
Principal Investigator: Boris Labar         
France
Hôpital Saint Antoine AP-HP Not yet recruiting
Paris, France
Principal Investigator: Olivier Legrand         
Italy
Univesita Degli Studi "La Sapienza" Recruiting
Roma, Italy
Principal Investigator: Giovanna Meloni         
Azienda Ospedallera Universitaria - Policlinico Tor Vergata Recruiting
Roma, Italy
Principal Investigator: Sergio Amadori         
Netherlands
Leiden University Medical Center Active, not recruiting
Leiden, Netherlands
Radboud University Nijmegen Medical Center Recruiting
Nijmegen, Netherlands
Principal Investigator: Petra Muus         
Jeroen Bosch Ziekenhuis Recruiting
s' Hertogenbosch, Netherlands
Principal Investigator: Hans Pruijt         
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
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
  More Information

Additional Information:
No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00838240     History of Changes
Other Study ID Numbers: EORTC-06061, EORTC-06061, EU-20905, 2006-004912-28, GIMEMA-AML-14A
Study First Received: February 5, 2009
Last Updated: July 19, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Istituto Superiore di Sanita

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cytarabine
Clofarabine
Idarubicin
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
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014