Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00027872
• Other study ID #: NCI-2012-02980
• Secondary ID: UMGCC 0116U01CA0
• Status: Completed
• Phase: Phase 2
• First received: December 7, 2001
• Last updated: March 22, 2013
• Start date: October 2001
• Est. completion date: January 2009

Study information

• Verified date: March 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: January 2009
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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
• Hypereosinophilic Syndrome
• Leukemia
• Leukemia, Erythroblastic, Acute
• Leukemia, Megakaryoblastic, Acute
• Leukemia, Monocytic, Acute
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Myelodysplastic Syndromes
• Preleukemia
• Untreated Adult Acute Myeloid Leukemia

Intervention

Drug:
• tipifarnib
Given orally

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission (CR) rate	CR rates will be calculated with 95% confidence intervals for each age group separately.	Up to 8 years	No
Secondary	Partial remission (PR) rate	Will be estimated by observed proportions and 95% confidence intervals.	Up to 8 years	No
Secondary	Toxicity rates assessed using NCI CTCAE version 3.0	Will be estimated by observed proportions and 95% confidence intervals.	Up to 8 years	No
Secondary	Duration of response	Duration of response and survival will be summarized by the Kaplan-Meier estimate of the survival distribution.	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	No
Secondary	Duration of survival	Duration of response and survival will be summarized by the Kaplan-Meier estimate of the survival distribution.	From time of enrollment onto this study to the time of death, assessed up to 8 years	No