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:
European Organisation for Research and Treatment of Cancer - EORTC
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
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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
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 |
ClinicalTrials.gov processed this record on May 16, 2013