A Phase 1 interventional study of tipifarnib and etoposide in Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0) and Adult Acute Monoblastic Leukemia (M5a), sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 70 Years and older. Per ClinicalTrials.gov, last updated 2013-01-09.
Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment
This phase I trial is studying the side effects and best dose of tipifarnib and etoposide in treating older patients with newly diagnosed acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving tipifarnib together with etoposide may kill more cancer cells
PRIMARY OBJECTIVES:
I. To determine the feasibility, tolerability, and toxicities of administering a fixed dose of R115777 in combination with escalating doses of VP-16 in elderly adults ( = 70 years) with newly diagnosed, previously untreated acute myelogenous leukemia (AML).
II. To determine the maximal tolerated dose (MTD) of R115777 + VP-16 combination, including the duration of R115777 administration, for future Phase II trials.
III. To obtain preliminary descriptive data regarding the effects of R115777 + VP-16 on cell cycle progression and apoptosis in AML marrow cells.
IV. To study mechanisms of leukemia cell resistance to R115777 in combination with etoposide.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive oral tipifarnib twice daily on days 1-14 OR 1-21 and oral etoposide once daily on days 1-3 and 8-10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) may receive up to 5 additional courses of therapy beyond documentation of CR.
Cohorts of 3-6 patients receive escalating doses of tipifarnib and etoposide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 14 additional patients receive treatment at the MTD.
After completion of study treatment, patients are followed at 1 month and then every 3 months thereafter.
PROJECTED ACCRUAL: A total of 3-100 patients will be accrued for this study.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 100 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
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Disease-specific criteria:
Exclusion Criteria:
Patients receive oral tipifarnib twice daily on days 1-14 OR 1-21 and oral etoposide once daily on days 1-3 and 8-10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a CR may receive up to 5 additional courses of therapy beyond documentation of CR. Cohorts of 3-6 patients receive escalating doses of tipifarnib and etoposide until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 14 additional patients receive treatment at the MTD.
Drug: tipifarnib · Drug: etoposide
Given orally
Also known as: R115777, Zarnestra
Given orally
Also known as: EPEG, VP-16, VP-16-213
Number of patients who experience dose limiting toxicities (DLT), based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
Time frame: Up to 28 days
Clinical response in terms of optimal dose combination for further study
A response surface will be constructed using a flexible two dimensional polynomial.
Time frame: Up to 4 years
Clinical tolerance in terms of additive or synergistic non-hematologic toxicities grade 2 or greater
A response surface will be constructed using a flexible two dimensional polynomial.
Time frame: Up to 4 years
Surrogates of response in terms of cell cycle progression and apoptosis, deoxyribonucleic acid (DNA) damage, and results of in vitro model studies (using pre-post assessments).
A response surface will be constructed using a flexible two dimensional polynomial.
Time frame: Up to day 63
This study is completed, as verified in Jan 2013. You cannot join it, but the record below documents what was studied.
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National Cancer Institute (NCI)