Idarubicin, Cytarabine, and Tipifarnib in Treating Patients With Newly Diagnosed Myelodysplastic Syndromes or Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT00096122

Recruitment Status : Completed

First Posted : November 9, 2004

Results First Posted : July 15, 2011

Last Update Posted : May 26, 2014

Sponsor:

Information provided by (Responsible Party):

National Cancer Institute (NCI)

Study Description

Brief Summary:

This phase I/II trial is studying the side effects and best dose of tipifarnib when given with idarubicin and cytarabine and to see how well it works in treating patients with newly diagnosed myelodysplastic syndromes or acute myeloid leukemia. Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Tipifarnib (Zarnestra) may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Giving idarubicin and cytarabine with tipifarnib may kill more cancer cells.

Condition or disease	Intervention/treatment	Phase
Adult Acute Basophilic Leukemia Adult Acute Eosinophilic Leukemia Adult Acute Megakaryoblastic Leukemia (M7) Adult Acute Minimally Differentiated Myeloid Leukemia (M0) Adult Acute Monoblastic Leukemia (M5a) Adult Acute Monocytic Leukemia (M5b) Adult Acute Myeloblastic Leukemia With Maturation (M2) Adult Acute Myeloblastic Leukemia Without Maturation (M1) Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Acute Myelomonocytic Leukemia (M4) Adult Erythroleukemia (M6a) Adult Pure Erythroid Leukemia (M6b) Childhood Myelodysplastic Syndromes Chronic Myelomonocytic Leukemia de Novo Myelodysplastic Syndromes Refractory Anemia With Excess Blasts Refractory Anemia With Excess Blasts in Transformation Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Untreated Adult Acute Myeloid Leukemia	Drug: cytarabine Drug: idarubicin Drug: tipifarnib	Phase 1 Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the tolerability of the combination of R115777 (Zarnestra™) and Idarubicin plus cytarabine by defining the DLT and MTD. (Phase I) II. To determine the efficacy of the combination of Idarubicin, cytarabine and ZARNESTRA in patients with high-risk MDS and AML. (Phase II)

OUTLINE: This is a dose-escalation study of tipifarnib. Patients are stratified according to age (< 50 versus ≥ 50) and, in patients ≥ 50 years of age, cytogenetics (diploid versus unfavorable).

INDUCTION THERAPY:

PHASE I: Patients receive cytarabine IV continuously on days 1-3 (or 1-4), idarubicin intravenous (IV) over 1 hour on days 1-3, and oral tipifarnib twice daily on days 1-21. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

PHASE II: Patients receive cytarabine, idarubicin, and tipifarnib as in phase I at the MTD.

Patients in both phases who respond to induction therapy proceed to consolidation maintenance therapy.

CONSOLIDATION MAINTENANCE THERAPY: Patients receive consolidation therapy comprising cytarabine IV continuously on days 1-3, idarubicin IV over 1 hour on days 1-2, and tipifarnib twice daily on days 1-14. Treatment repeats every 4-6 weeks for 5 courses in the absence of unacceptable toxicity.

Patients then begin maintenance therapy comprising oral tipifarnib twice daily on day 1-21. Treatment repeats every 4-6 weeks for 6 courses in the absence of unacceptable toxicity.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	95 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	PHASE I-II STUDY OF IDARUBICIN, CYTARABINE AND R115777 (TIPIFARNIB, ZARNESTRA; 702818; IND 58359), A FARNESYLTRANSFERASE INHIBITOR, IN PATIENTS WITH HIGH-RISK MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIAS
Study Start Date :	September 2004
Actual Primary Completion Date :	September 2006
Actual Study Completion Date :	February 2010

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Core binding factor acute myeloid leukemia Cytogenetically normal acute myeloid leukemia Familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Leukemia Myelodysplastic Syndromes

Drug Information available for: Cytarabine Idarubicin hydrochloride Idarubicin

Genetic and Rare Diseases Information Center resources: Myelodysplastic Syndromes Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Chronic Myelomonocytic Leukemia Juvenile Myelomonocytic Leukemia Acute Myeloblastic Leukemia With Maturation Acute Myeloblastic Leukemia Without Maturation Acute Erythroid Leukemia Acute Megakaryoblastic Leukemia Acute Myelomonocytic Leukemia Di Guglielmo's Syndrome Acute Monoblastic Leukemia Hypereosinophilic Syndrome Myelodysplastic/myeloproliferative Disease Chronic Myeloproliferative Disorders

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm I See Detailed Description	Drug: cytarabine Given IV Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside Drug: idarubicin Given IV Other Names: 4-demethoxydaunorubicin 4-DMDR DMDR IDA Drug: tipifarnib Given orally Other Names: R115777 Zarnestra

Outcome Measures

Primary Outcome Measures :

Number of Participants With Complete Response [ Time Frame: 21 Day Cycle ]
Complete Response (CR) is required bone marrow blasts ≤5% and recovery of normal hematopoiesis with an absolute neutrophil count (ANC) of 1*10^9/L or more and platelet count of 100*10^9/L or more; and a complete response without platelets (CRp) is the same criteria as CR but with platelet counts from 20*10^9/L to less than 100*10^9/L.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	15 Years to 70 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of 1) AML (WHO classification definition of > 20% blasts), or 2) high risk MDS (defined as the presence of > 10% blasts)
Patients must be chemo-naïve, i.e. not have received any prior chemotherapy (except hydrea) for AML or MDS; they could have received transfusions, hematopoietic growth factors or vitamins; temporary measures such as pheresis or hydrea (0.5 to 5g daily for up to 3 days) are allowed
ECOG PS of 0-1 at screening
Creatinine =< 2 mg/dl
Total bilirubin =< 2 mg/dL, unless increase is due to hemolysis
Transaminases (SGPT) =< 2.5 x ULN
Ability to take oral medication
Ability to understand and provide signed informed consent

Exclusion Criteria:

Subjects with APL
Presence of active systemic infection
Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results
Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (such as birth control pills, IUD, diaphragm, abstinence, or condoms by their partner) over the entire course of the study
Known allergy to imidazole drugs (such as clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, tioconazole, terconazole)

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00096122

Locations


United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Jorge Cortes	M.D. Anderson Cancer Center

More Information


Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00096122 History of Changes
Other Study ID Numbers:	NCI-2012-02862 2003-0563 6625 N01CM62202 ( U.S. NIH Grant/Contract )
First Posted:	November 9, 2004 Key Record Dates
Results First Posted:	July 15, 2011
Last Update Posted:	May 26, 2014
Last Verified:	June 2013

Additional relevant MeSH terms:


Syndrome Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Anemia Myelodysplastic Syndromes Preleukemia Neoplasm Metastasis Leukemia, Myelomonocytic, Acute Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Anemia, Refractory Anemia, Refractory, with Excess of Blasts Leukemia, Monocytic, Acute Hypereosinophilic Syndrome	Leukemia, Megakaryoblastic, Acute Leukemia, Erythroblastic, Acute Anemia, Aplastic Leukemia, Basophilic, Acute Leukemia, Eosinophilic, Acute Disease Pathologic Processes Neoplasms by Histologic Type Neoplasms Hematologic Diseases Bone Marrow Diseases Precancerous Conditions Neoplastic Processes Myelodysplastic-Myeloproliferative Diseases Eosinophilia

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