Clinical trial NCT00027872: Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 125
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

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 criteria: 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

Primary outcomes:
measure: Complete remission (CR) rate
timeFrame: Up to 8 years
Secondary outcomes:
measure: Partial remission (PR) rate
timeFrame: Up to 8 years
measure: Toxicity rates assessed using NCI CTCAE version 3.0
timeFrame: Up to 8 years
measure: Duration of response
timeFrame: 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
measure: Duration of survival
timeFrame: From time of enrollment onto this study to the time of death, assessed up to 8 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Judith Karp
role: PRINCIPAL_INVESTIGATOR
References: