Trial Outcomes & Findings for Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia (NCT NCT01361464)

Last Updated: 2015-04-08

Results Overview

Complete Remission (CR) rate in Acute Myelogenous Leukemia (AML) patients prospectively selected for R115777R115777 (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates. AML Complete Remission: Bone marrow aspiration - Less than 5% leukemic blasts, Auer rods not detected; Peripheral blood counts - Absolute neutrophil count \>/= 1,000/mm\^3, Platelet count \>/= 100,000/mm\^3, Leukemic blasts not present; Blood-product transfusion independence; Absence of extramedullary leukemia.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

From first treatment through follow up period, an expected average of 12 months

Results posted on

2015-04-08

Participant Flow

The Southeast Phase II Consortium (SEP2C) enrolled participants at 3 cancer centers in the United States. The study opened to accrual on 5/24/2011 and closed to accrual 07/25/2012. Further development of Tipifarnib in acute myeloid leukemia (AML) was terminated after the study failed to meet the primary endpoint.

Participant milestones

Participant milestones
Measure	R115777 Therapy Each participant will begin R115777 treatment with an orally dosed regimen of 300 mg twice a day (BID) for the first 21 consecutive days of a 28-day cycle.
Overall Study STARTED	21
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	R115777 Therapy Each participant will begin R115777 treatment with an orally dosed regimen of 300 mg twice a day (BID) for the first 21 consecutive days of a 28-day cycle.
Overall Study Death	1
Overall Study Withdrawal by Subject	2

Baseline Characteristics

Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	R115777 Therapy n=21 Participants Each participant will begin R115777 treatment with an orally dosed regimen of 300 mg twice a day (BID) for the first 21 consecutive days of a 28-day cycle.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	21 Participants n=5 Participants
Age, Continuous	75 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants

PRIMARY outcome

Timeframe: From first treatment through follow up period, an expected average of 12 months

Population: All evaluable participants

Outcome measures

Outcome measures
Measure	R115777 Therapy n=18 Participants Each participant will begin R115777 treatment with an orally dosed regimen of 300 mg twice a day (BID) for the first 21 consecutive days of a 28-day cycle.
Complete Remission (CR) Rate	11 percentage of participants

SECONDARY outcome

Timeframe: From first treatment through follow up period, an expected average of 12 months

Population: All evaluable participants

Overall survival is calculated from the first day of R115777 treatment and lasts until the date of death recorded on the case report form (CRF).

Outcome measures

Outcome measures
Measure	R115777 Therapy n=18 Participants Each participant will begin R115777 treatment with an orally dosed regimen of 300 mg twice a day (BID) for the first 21 consecutive days of a 28-day cycle.
Median Overall Survival (OS)	6.6 months Interval 4.2 to Not Reached. Data is through through 12/2012. Updates will be submitted as appropriate.

SECONDARY outcome

Timeframe: 1 year

Population: Evaluable participants at planned study completion date

Prior to the early discontinuation of the study (for not meeting the primary endpoint of at least 3 CR/CRi after 2 cycles), investigators had planned to calculate one year survival from Kaplan Meier estimates.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 7 months

Population: All evaluable participants

Relapse-free survival is calculated from the date of documentation of complete remission/morphologic complete remission with incomplete blood count recovery (CR/CRi) until disease relapse or death from any cause.

Outcome measures

Outcome measures
Measure	R115777 Therapy n=18 Participants Each participant will begin R115777 treatment with an orally dosed regimen of 300 mg twice a day (BID) for the first 21 consecutive days of a 28-day cycle.
Number of Participants With Relapse Free Survival	2 participants

Adverse Events

R115777 Therapy

Serious events: 7 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	R115777 Therapy n=21 participants at risk Each participant will begin R115777 treatment with an orally dosed regimen of 300 mg twice a day (BID) for the first 21 consecutive days of a 28-day cycle.
Blood and lymphatic system disorders Febrile neutropenia	19.0% 4/21 • Number of events 5 • 19 months
Cardiac disorders Sinus tachycardia	4.8% 1/21 • Number of events 1 • 19 months
Gastrointestinal disorders Nausea	4.8% 1/21 • Number of events 2 • 19 months
Gastrointestinal disorders Vomiting	4.8% 1/21 • Number of events 2 • 19 months
General disorders Chills	4.8% 1/21 • Number of events 1 • 19 months
General disorders Fatigue	4.8% 1/21 • Number of events 1 • 19 months
General disorders Fever	4.8% 1/21 • Number of events 1 • 19 months
General disorders General disorders and administration site conditions - Other	4.8% 1/21 • Number of events 1 • 19 months
Infections and infestations Infections and infestations - Other	4.8% 1/21 • Number of events 1 • 19 months
Infections and infestations Lung infection	9.5% 2/21 • Number of events 3 • 19 months
Infections and infestations Upper respiratory infection	4.8% 1/21 • Number of events 1 • 19 months
Injury, poisoning and procedural complications Fall	4.8% 1/21 • Number of events 1 • 19 months
Investigations Neutrophil count decreased	4.8% 1/21 • Number of events 1 • 19 months
Musculoskeletal and connective tissue disorders Generalized muscle weakness	4.8% 1/21 • Number of events 2 • 19 months

Other adverse events

Other adverse events
Measure	R115777 Therapy n=21 participants at risk Each participant will begin R115777 treatment with an orally dosed regimen of 300 mg twice a day (BID) for the first 21 consecutive days of a 28-day cycle.
Blood and lymphatic system disorders Febrile neutropenia	38.1% 8/21 • Number of events 11 • 19 months
Blood and lymphatic system disorders Anemia	19.0% 4/21 • Number of events 5 • 19 months
General disorders Fatigue	38.1% 8/21 • Number of events 10 • 19 months
General disorders General disorders and administration site conditions - Other	14.3% 3/21 • Number of events 3 • 19 months
General disorders Chills	9.5% 2/21 • Number of events 3 • 19 months
General disorders Edema - face	9.5% 2/21 • Number of events 3 • 19 months
General disorders Fever	9.5% 2/21 • Number of events 2 • 19 months
General disorders Non-cardiac chest pain	9.5% 2/21 • Number of events 3 • 19 months
General disorders Pain	9.5% 2/21 • Number of events 4 • 19 months
Gastrointestinal disorders Nausea	33.3% 7/21 • Number of events 10 • 19 months
Gastrointestinal disorders Diarrhea	28.6% 6/21 • Number of events 9 • 19 months
Gastrointestinal disorders Vomiting	28.6% 6/21 • Number of events 8 • 19 months
Gastrointestinal disorders Constipation	14.3% 3/21 • Number of events 3 • 19 months
Gastrointestinal disorders Mucositis - oral	9.5% 2/21 • Number of events 2 • 19 months
Infections and infestations Lung infection	19.0% 4/21 • Number of events 4 • 19 months
Infections and infestations Sepsis	14.3% 3/21 • Number of events 3 • 19 months
Investigations White blood cell decreased	33.3% 7/21 • Number of events 9 • 19 months
Investigations Platelet count decreased	23.8% 5/21 • Number of events 10 • 19 months
Investigations Neutrophil count decreased	9.5% 2/21 • Number of events 2 • 19 months
Skin and subcutaneous tissue disorders Rash maculo-papular	23.8% 5/21 • Number of events 7 • 19 months
Skin and subcutaneous tissue disorders Pruritus	19.0% 4/21 • Number of events 6 • 19 months
Metabolism and nutrition disorders Anorexia	33.3% 7/21 • Number of events 8 • 19 months
Metabolism and nutrition disorders Hypokalemia	9.5% 2/21 • Number of events 4 • 19 months
Nervous system disorders Dizziness	19.0% 4/21 • Number of events 6 • 19 months
Nervous system disorders Headache	9.5% 2/21 • Number of events 2 • 19 months
Nervous system disorders Syncope	9.5% 2/21 • Number of events 2 • 19 months
Respiratory, thoracic and mediastinal disorders Dyspnea	28.6% 6/21 • Number of events 6 • 19 months
Respiratory, thoracic and mediastinal disorders Epistaxis	9.5% 2/21 • Number of events 2 • 19 months
Respiratory, thoracic and mediastinal disorders Wheezing	9.5% 2/21 • Number of events 2 • 19 months
Musculoskeletal and connective tissue disorders Back pain	9.5% 2/21 • Number of events 3 • 19 months
Musculoskeletal and connective tissue disorders Pain in extremity	9.5% 2/21 • Number of events 3 • 19 months
Psychiatric disorders Confusion	14.3% 3/21 • Number of events 4 • 19 months
Psychiatric disorders Insomnia	14.3% 3/21 • Number of events 5 • 19 months
Psychiatric disorders Delirium	9.5% 2/21 • Number of events 2 • 19 months
Renal and urinary disorders Urinary frequency	14.3% 3/21 • Number of events 4 • 19 months
Renal and urinary disorders Urinary incontinence	9.5% 2/21 • Number of events 2 • 19 months
Injury, poisoning and procedural complications Fall	14.3% 3/21 • Number of events 3 • 19 months
Injury, poisoning and procedural complications Bruising	9.5% 2/21 • Number of events 3 • 19 months

Additional Information

Jeffrey Lancet, M.D.

H. Lee Moffitt Cancer Center and Research Institute

Phone: 813-745-6841

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60