Clofarabine, Cytarabine, and Idarubicin in Treating Patients With Intermediate-Risk or High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplasia
Information source: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia; Myelodysplastic Syndromes
Intervention: clofarabine (Drug); cytarabine (Drug); idarubicin (Drug)
Phase: Phase 1/Phase 2
Status: Recruiting
Sponsored by: European Organisation for Research and Treatment of Cancer - EORTC Official(s) and/or principal investigator(s): Roel Willemze, Principal Investigator, Affiliation: EORTC (Phase I) - Leiden University Medical Center, NL Dominik Selleslag, Principal Investigator, Affiliation: EORTC (Phase II) - AZ Sint-Jan, BE Giovanna Meloni, Principal Investigator, Affiliation: GIMEMA (Phase I & II) - Universita Degli Studi "La Sapienza", IT
Overall contact: Hilde Breyssens, Email: hilde.breyssens@eortc.be
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.
Clinical Details
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)
Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Toxicity as assessed by CTCAE v3.0 (Phase I)Response rate (Phase II)
Secondary outcome: 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 Incidence of relapse and incidence of death in CR/CRi
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
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
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)
Locations and Contacts
Hilde Breyssens, Email: hilde.breyssens@eortc.be
A.Z. Sint-Jan, Brugge, Belgium; Recruiting Dominik Selleslag, Principal Investigator
Institut Jules Bordet, Brussel, Belgium; Not yet recruiting Dominique Bron, Principal Investigator
CHU Sart-Tilman, Liège, Belgium; Not yet recruiting Frédéric Baron, Principal Investigator
University Hospital Rebro, Zagreb, Croatia; Not yet recruiting Boris Labar, Principal Investigator
Hôpital Saint Antoine AP-HP, Paris, France; Not yet recruiting Olivier Legrand, Principal Investigator
Azienda Ospedallera Universitaria - Policlinico Tor Vergata, Roma, Italy; Recruiting Sergio Amadori, Principal Investigator
Univesita Degli Studi "La Sapienza", Roma, Italy; Recruiting Giovanna Meloni, Principal Investigator
Leiden University Medical Center, Leiden, Netherlands; Active, not recruiting
Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; Recruiting Petra Muus, Principal Investigator
Jeroen Bosch Ziekenhuis, s' Hertogenbosch, Netherlands; Recruiting Hans Pruijt, Principal Investigator
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: November 2008
Last updated: July 19, 2012
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