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

Leukemia Clinical Trial

— AML-14A  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00838240
• Other study ID #: EORTC-06061
• Secondary ID: EORTC-06061EU-20
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: February 5, 2009
• Last updated: July 19, 2012
• Start date: November 2008

Study information

• Verified date: July 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: Hilde Breyssens
• Email: hilde.breyssens[@]eortc.be
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsNetherlands: 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
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 114
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• clofarabine
Given IV
• cytarabine
Given IV
• idarubicin
Given IV

Locations

Country	Name	City	State
Belgium	A.Z. Sint-Jan	Brugge
Belgium	Institut Jules Bordet	Brussel
Belgium	CHU Sart-Tilman	Liège
Croatia	University Hospital Rebro	Zagreb
France	Hôpital Saint Antoine AP-HP	Paris
Italy	Azienda Ospedallera Universitaria - Policlinico Tor Vergata	Roma
Italy	Univesita Degli Studi "La Sapienza"	Roma
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Radboud University Nijmegen Medical Center	Nijmegen
Netherlands	Jeroen Bosch Ziekenhuis	s' Hertogenbosch

Sponsors (2)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Gruppo Italiano Malattie EMatologiche dell'Adulto

Countries where clinical trial is conducted

Belgium,  Croatia,  France,  Italy,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity as assessed by CTCAE v3.0 (Phase I)			Yes
Primary	Response rate (Phase II)			No
Secondary	Toxicity as assessed by CTCAE v3.0 (Phase II)			Yes
Secondary	Response rate (Phase I)			No
Secondary	Duration of survival			No
Secondary	Duration of survival from complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate			No
Secondary	Disease-free survival from CR/CRi			No
Secondary	Incidence of relapse and incidence of death in CR/CRi			No