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)
18 Years
60 Years
Both
Leukemia, Myelodysplastic Syndromes
Trial Information
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)
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.
Inclusion 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)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Toxicity as assessed by CTCAE v3.0 (Phase I)
Safety Issue:
Yes
Principal Investigator
Roel Willemze
Investigator Role:
Principal Investigator
Investigator Affiliation:
EORTC (Phase I) - Leiden University Medical Center, NL
Authority:
Belgium: Federal Agency for Medicinal Products and Health Products
Study ID:
EORTC-06061
NCT ID:
NCT00838240
Start Date:
November 2008
Completion Date:
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- 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
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Myelodysplastic Syndromes
- Preleukemia
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