Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
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Purpose
Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Phase II trial to study the effectiveness of tipifarnib in treating older patients who have previously untreated acute myeloid leukemia
| Condition | Intervention | Phase |
|---|---|---|
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Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome Adult Acute Basophilic Leukemia Adult Acute Eosinophilic Leukemia Adult Acute Erythroid Leukemia (M6) Adult Acute Megakaryoblastic Leukemia (M7) Adult Acute Minimally Differentiated Myeloid Leukemia (M0) Adult Acute Monoblastic Leukemia (M5a) Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5) 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 Del(5q) 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) Cellular Diagnosis, Adult Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia |
Drug: tipifarnib Other: laboratory biomarker analysis |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Study of Farnesyl Transferase Inhibitor R115777 (Zarnestra) (R115777 ( Zarnestra), Tipifarnib, R115777, NSC #702818) in Elderly Patients With Previously Untreated Poor-Risk Acute Myeloid Leukemia |
- Complete remission (CR) rate [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]CR rates will be calculated with 95% confidence intervals for each age group separately.
- Partial remission (PR) rate [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]Will be estimated by observed proportions and 95% confidence intervals.
- Toxicity rates assessed using NCI CTCAE version 3.0 [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]Will be estimated by observed proportions and 95% confidence intervals.
- Duration of response [ Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 8 years ] [ Designated as safety issue: No ]Duration of response and survival will be summarized by the Kaplan-Meier estimate of the survival distribution.
- Duration of survival [ Time Frame: From time of enrollment onto this study to the time of death, assessed up to 8 years ] [ Designated as safety issue: No ]Duration of response and survival will be summarized by the Kaplan-Meier estimate of the survival distribution.
| Enrollment: | 125 |
| Study Start Date: | October 2001 |
| Study Completion Date: | January 2009 |
| Primary Completion Date: | July 2007 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (tipifarnib)
Patients receive oral tipifarnib twice daily on days 1-21. Patients with a complete or partial response, hematologic improvement, or stable disease continue treatment every 29-63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response after the second course of therapy receive 2 additional courses of therapy.
|
Drug: tipifarnib
Given orally
Other Names:
Other: laboratory biomarker analysis
Correlative studies
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Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the complete response rate of R115777 (tipifarnib) in previously untreated acute myeloid leukemia (AML) in (a) elderly patients (age >= 75) and (b) patients (age >= 65) with AML preceded by myelodysplastic syndrome (MDS), using a chronic dosing schedule.
SECONDARY OBJECTIVES:
I. To determine progression-free and overall survival in patients with previously untreated AML treated with R115777, using a chronic dosing schedule.
II. To determine the duration of response in patients with previously untreated AML treated with R115777, using a chronic dosing schedule.
III. To determine the effect of R115777 on the phosphorylation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3K) in leukemic cells.
IV. To determine the effect of R115777 on processing of the farnesylated protein HDJ-2.
V. To determine the toxicities of R115777 when given in a chronic dosing schedule.
OUTLINE: This is a multicenter study.
Patients receive oral tipifarnib twice daily on days 1-21. Patients with a complete or partial response, hematologic improvement, or stable disease continue treatment every 29-63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response after the second course of therapy receive 2 additional courses of therapy.
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 125 patients will be accrued for this study within 11-17 months.
Eligibility| Ages Eligible for Study: | 65 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Pathologic confirmation of the diagnosis of AML (>= 20% marrow blasts)
- ECOG performance status 0 or 1
- Patients must be able to give informed consent
- SGOT and SGPT =< 2.5 x normal limits (grade 1)
- Serum creatinine =< 1.5 x normal limits (grade 1)
AML (any of the following):
- Newly diagnosed AML in adults >= 75 years
- Newly diagnosed AML arising from MDS in adults >= 65 years
- Hyperleukocytosis with >= 30,000 leukemic blasts/uL
Exclusion Criteria:
- Acute promyelocytic (FAB M3) subtype
- Previously treated with chemotherapy for leukemia (except for hydroxyurea)
- Disseminated intravascular coagulation (laboratory or clinical)
- Active central nervous system leukemia
- Concomitant radiation therapy, chemotherapy, or immunotherapy; previous therapy for another malignancy is permitted, provided that at least 1 month has occurred since patient received any of these treatments
- Intrinsic impaired organ function (as stated above)
- Symptomatic neuropathy (grade 2 or worse)
- Known allergy to imidazole drugs, such as ketoconazole, miconazole, econazole, teconazole, clotrimazole, fenticonazole, isoconazole, sulconazole, or ticonazole
- Physical or psychiatric conditions that in the estimation of the principal investigator (PI) or designee place the patient at high risk of toxicity or non-compliance, e.g. severe congestive heart failure (CHF), unstable angina, or poorly controlled psychosis
Contacts and Locations More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00027872 History of Changes |
| Other Study ID Numbers: | NCI-2012-02980, UMGCC 0116, U01CA069854, U01CA070095 |
| Study First Received: | December 7, 2001 |
| Last Updated: | March 22, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Congenital Abnormalities Leukemia Leukemia, Basophilic, Acute Leukemia, Eosinophilic, Acute Leukemia, Erythroblastic, Acute Leukemia, Megakaryoblastic, Acute Leukemia, Monocytic, Acute Leukemia, Myeloid, Acute Leukemia, Myeloid Leukemia, Myelomonocytic, Acute Myelodysplastic Syndromes Preleukemia Leukemia, Myelomonocytic, Chronic Hypereosinophilic Syndrome |
Neoplasms by Histologic Type Neoplasms Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Myelodysplastic-Myeloproliferative Diseases Eosinophilia Leukocyte Disorders Tipifarnib Antineoplastic Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 21, 2013