Download - Zarnestra NDA 21824
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ZarnestraZarnestra NDA NDA 2182421824
Qin Ryan MD, PhDQin Ryan MD, PhD
DODP/CDER/FDADODP/CDER/FDA
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OutlineOutline Regulatory BackgroundRegulatory Background Clinical Overview and Clinical Overview and
Proposed IndicationProposed Indication CTEP-20 DesignCTEP-20 Design CTEP-20 EfficacyCTEP-20 Efficacy CTEP-20 SafetyCTEP-20 Safety SummarySummary
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Regulatory Regulatory BackgroundBackground
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Regulatory BackgroundRegulatory Background In oncology, clinical benefit (CB) has been In oncology, clinical benefit (CB) has been
defined as a longer life, a better life or an defined as a longer life, a better life or an effect on an established surrogate for eithereffect on an established surrogate for either
In acute leukemias, durable complete In acute leukemias, durable complete remission (CR) has been considered remission (CR) has been considered evidence of benefitevidence of benefit
In some cases where leukemia CR’s were of In some cases where leukemia CR’s were of uncertain duration, CR was considered a uncertain duration, CR was considered a surrogate reasonably likely to predict CBsurrogate reasonably likely to predict CB
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Drug Approvals for AMLDrug Approvals for AMLDrug Indication Trial (s) Benefit
Idarubicin First-linecombination
4 randomizedtrials
CR 67-78% withAra-C versus 55-58% fordauno/Ara-CSurvival
Daunorubicin Remissioninduction
Single arm andrandomized
40-50% CR rate;53%-65% CRrate with Ara-C
Gemtuzumabozogamicin
Second-line, >60, CD33+,cannot toleratechemo
3 single armtrials
CR = 16%CR + CRp =30%
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Clinical Clinical OverviewOverview
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Induction Therapy for AML Induction Therapy for AML Untreated AML progresses rapidly to Untreated AML progresses rapidly to
deathdeath
Standard Rx in Adults < 60: Standard Rx in Adults < 60: 60-75% CR 60-75% CR < 20% treatment related death< 20% treatment related death DFS 20-50%DFS 20-50% 30-40% survive 30-40% survive >> 3 years 3 years
Factors affecting outcome: PS, organ Factors affecting outcome: PS, organ function, co-morbidity, age, function, co-morbidity, age, karyotype
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Induction Chemotherapy for Induction Chemotherapy for Elderly Patients with AMLElderly Patients with AML
Age 65-74 years (N=1,132)
75-84 years (N=1,082)
>85 years(N=433)
Total(N=2,657)
Received chemotherapy
44% 24% 6% 30%
Menzin et al., Arch Intern Med 2002, 162: 1597.
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Survival in Elderly Patients Survival in Elderly Patients with AMLwith AML
Menzin et al., Arch Intern Med 2002, 162: 1597.
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Elderly Patients with Poor-Elderly Patients with Poor-Risk AMLRisk AML
Higher mortality and morbidity seen Higher mortality and morbidity seen in elderly patients with poor-risk AML in elderly patients with poor-risk AML receiving standard chemotherapy receiving standard chemotherapy
Outcome Age < 65 Age >65 + Other factors
Treatment related death 10-20% > 25%
Complete remission rate 60-75% 30% - 50%
Survival rate 30-40% > 3 years < 6% at 2 years
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Clinical ProgramClinical Program
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ZarnestraZarnestra
Farnesyl transferase inhibitorFarnesyl transferase inhibitor
100 mg Tablets 100 mg Tablets
600 mg twice daily PO for 21 days, 600 mg twice daily PO for 21 days, followed by a rest period of 7 - 42 followed by a rest period of 7 - 42 daysdays
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Proposed IndicationProposed Indication
Treatment of elderly patients with Treatment of elderly patients with newly diagnosed poor-risk acute newly diagnosed poor-risk acute myeloid leukemia.myeloid leukemia.
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Zarnestra NDA: AML Zarnestra NDA: AML TrialsTrials
Clinical Study
Elderly poor-risk AML / AML
(Total Enrolled)
Study Description Endpoints
CTEP-20* 136 / 157(N=171)
Single arm, open label, previously untreated elderly poor-risk AML patients
Efficacy and safety
INT-17 99 / 252(N= 252)
Single arm, open label, refractory or relapsed AML patients
Efficacy, safety, and PK
CTEP-1* 14 / 25(N = 34)
Single arm, open label, dose escalation in hematologic malignancies
Phase 2 recommended dose, PK and tolerability
* Conducted by NCI, CTEP as part of a Cooperative Research and Development Agreement with J&J
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CTEP-20 DesignCTEP-20 Design
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CTEP-20 DesignCTEP-20 Design
Open-label, single-arm, multicenterOpen-label, single-arm, multicenter PopulationPopulation
Original: untreated poor-risk Original: untreated poor-risk hematological malignancieshematological malignancies
66thth amendment (after 110 amendment (after 110 enrollments): untreated elderly enrollments): untreated elderly poor-risk AMLpoor-risk AMLAge > 75Age > 75Age 65-74 AML with prior MDSAge 65-74 AML with prior MDS
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CTEP-20 DesignCTEP-20 Design Primary objective Primary objective
Original: RR (CR+PR)Original: RR (CR+PR) 66thth amendment: complete response (CR) rate amendment: complete response (CR) rate
in untreated elderly poor-risk AMLin untreated elderly poor-risk AML
Secondary objectives: Secondary objectives: Progression-free survival (PFS)Progression-free survival (PFS) Overall survival (OS)Overall survival (OS) Duration of responseDuration of response Safety Safety
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CTEP-20 Major EligibilityCTEP-20 Major Eligibility
After amendment #6After amendment #6 Inclusion:Inclusion:
Untreated newly diagnosed AML Untreated newly diagnosed AML >> 75 75 65-74 with prior MDS65-74 with prior MDS
Confirmation with Confirmation with >> 20% BM or PB blasts 20% BM or PB blasts PS 0 or 1, adequate renal and liver PS 0 or 1, adequate renal and liver
functionfunction..
Exclusion: circulating blasts Exclusion: circulating blasts >> 30,000/uL, 30,000/uL, APL (M3), CNS leukemia, DICAPL (M3), CNS leukemia, DIC
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CTEP-20 Efficacy CTEP-20 Efficacy AssessmentAssessment
Medical history and physical examination, Medical history and physical examination, BM aspirate and biopsy, hematological and BM aspirate and biopsy, hematological and chemistry labs at baseline and the end of chemistry labs at baseline and the end of each cycleeach cycle
CR determined by NCI sponsored AML CR determined by NCI sponsored AML criteria criteria (Cheson et al., J Clin Oncol 8: 813-819, 1990)(Cheson et al., J Clin Oncol 8: 813-819, 1990)
Subsequent treatment and follow upSubsequent treatment and follow up
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CTEP-20 EfficacyCTEP-20 Efficacy
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CTEP-20 Study CTEP-20 Study PopulationPopulation
*One elderly patient with AML did not receive treatment by the time of clinical cut off.
Patient PopulationNumber of Patients
Sponsor FDA
All Enrolled 171 171
All Treated AML 157 156
Elderly poor-risk AMLAge 75 yearsAge 65-74 years with prior MDS
1367561
1357461
Non AML 13 (8) 14 (8)
MDSb 8 (5) 9 (5)
CMML 5 (3) 5 (3)
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CTEP-20 Elderly Poor-Risk AML CTEP-20 Elderly Poor-Risk AML Population: Demographics Population: Demographics
Number of subjects (%) 65-74 y prior > 75 y Total
Baseline ECOG performance status
60 73 133
0 19 (32) 13 (18) 32 (24)
1 35 (58) 51 (70) 86 (65)
2 6 (10) 9 (12) 15 (11)
Ineligible for chemotherapya 61 75 136
Age 34 (56) 72 (96) 106 (78)
Risk factors 31 (51) 29 (39) 60 (44)
Other 15 (25) 10 (13) 25 (18)
a Some subjects had more than 1 reason for ineligibility for chemotherapy.
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CTEP-20 Elderly Poor-Risk AML Population: CTEP-20 Elderly Poor-Risk AML Population: Risk Factors Risk Factors
Risk factor 65-74 y prior MDS(N= 61) n (%)
> 75 y (N= 75) n (%)
Total (N= 136) n (%)
Prior MDS 61 (100) 50 (67) 111 (82)
Baseline organ dysfunction 31 (51) 52 (69) 83 (61)
Age > 75 years - 75 (100) 75 (55)
Unfavorable karyotype 37 (61) 29 (39) 66 (49)
Number of risk factors per subject
1 10 (16) 4 (5) 14 (10)
2 34 (56) 26 (35) 60 (44)
3 17 (28) 30 (40) 47 (35)
4 - 15 (20) 15 (11)
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CTEP-20CTEP-20 Primary Endpoint: Primary Endpoint: CR RateCR Rate
Total (N= 135)
CR (%) CRu Unavailable for Assessment
Investigators 17 (13) 2 1
Independent Review
15 (11) 3 2
FDA 15 (11) 3 2
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CTEP-20 CR Rate Analysis CTEP-20 CR Rate Analysis by FDAby FDA
Confirmed CR / No. of Patients
CR Rate (n/N)[95% CI]
15 / 135 11.1%6.6 – 18.0%
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CTEP-20 CR Rate CTEP-20 CR Rate Subgroup Analysis by Subgroup Analysis by
FDAFDACategory Group
Confirmed CR / No. of Patients
CR Rate (n/N)[95% CI]
Age
65 – 74 years 10 /6116.4%
8.6 – 28.5%
≥ 75 years 5 / 746.8%
3.1 – 18.8%
Prior MDS
Yes 14 / 11012.7%
7.4 – 20.8%
No 1 / 254%
0.2 – 22.3%
Karyotype
Unfavorable 5 / 657.7%
0.1 – 9.4
Favorable 9 / 6214.5%
0.1 – 19.8
Unkown 1 / 812.5%
0.7 – 53.3%
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CTEP-20 CR DurationCTEP-20 CR Duration
Analysis FDA Results
Number failed/Number assessed 7/15 (47%)
Median duration in days [95% CI]275
[127 – 376]
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CTEP-20 SafetyCTEP-20 Safety
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CTEP-20 Safety – CTEP-20 Safety – ExposureExposure
Category, n (%) Cycle 1 136 (100)
Cycle 2 64 (47)
Cycle 3 27 (20)
Cycle duration
1-28 days 39 (29) 13 (20) 7 (26)
29-35 days 21 (15) 12 (19) 5 (19)
36-42 days 29 (21) 19 (30) 8 (30)
43-49 days 26 (19) 10 (16) 5 (19)
50-56 days 7 (5) 4 (6) -
57- 63 days 6 (4) 3 (5) 1 (4)
> 64 days 8 (6) 3 (5) 1 (4)
Mean (SD) 36.8 (16.88) 37.6 (15.06) 36.4 (14.39)
Median 38 38 36
Range (3; 92) (5; 75) (10; 85)
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CTEP-20 Safety – Dose CTEP-20 Safety – Dose IntensityIntensity
Category Cycle 1 (N= 136)
Cycle 2 (N= 64)
Cycle 3 (N= 27)
Dose intensity, mg/day
Mean (SD) 749.4 (277.40) 597.3 (251.93) 631.2 (282.9)
% of planned 63 50 53
Median 663.2 566.4 586.1
Range (273.9; 1200.0) (168.0; 1200.0) (197.6; 1200.0)
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CTEP-20 Safety –CTEP-20 Safety – Common Common AEsAEs
Non-Hematologic
diarrhea, fatigue, nausea, skin rash, fever, anorexia, constipation, vomiting, dyspnea, dizziness, ataxia or abnormal gait, confusion, bacterial infection, fungal infection
Hematologic neutropenia with or without fever, purpura, thrombocytopenia, anemia
Metabolic increased creatinine, hypokalemia, hyponatremia
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CTEP-20 SafetyCTEP-20 Safety Frequent Frequent AEs Leading to AEs Leading to
Treatment ChangeTreatment ChangeTreatment
ChangeIncidence
(n=136, %)Most Frequent AEs
Termination 21 (15) increased creatinine, rash, increased pancreatic enzymes
Dose Reduction
47 (35) neutropenia, ataxia, increased creatinine or abnormal renal function, confusion, diarrhea, increased pancreatic enzymes, rash
Interruption 56 (41) neutropenia, increased creatinine, nausea/vomiting, rash, confusion, pancytopenia
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CTEP-20 Safety – Grade 3/4 CTEP-20 Safety – Grade 3/4 AEsAEs
WHO Preferred Term Total N= 136 (%)
Total no. subjects 113 (83)
Neutropenia febrile 40 (29)
Infection bacterial 25 (18)
Thrombocytopenia 23 (17)
Neutropenia without fever 16 (12)
Pneumonia 14 (10)
Creatinine increased 12 (9)
Rash 12 (9)
Anemia 11 (8)
Diarrhea 8 (6)
Hypokalemia 8 (6)
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CTEP-20 Safety - DeathCTEP-20 Safety - Death
Cause of Death TotalN= 136 (%)
Deaths during the study 31 (23)
Progressive disease 19 (14)
Adverse event 9 (7)
Drug related 1 (1)
Other 3 (2)
Early deaths 16 (12)
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CTEP-20 – Hospitalization on Study CTEP-20 – Hospitalization on Study
No. of patient treated 136
Total no. of hospitalizations 141
No. of subjects hospitalized during study, n (%) 81 (60)
1-2 hospitalizations 71 (52)
3-4 hospitalizations 8 (6)
> 5 hospitalizations 2 (1)
Total duration of hospitalization, days
N 81
Mean (SD) 17.9 (14.38)
Median 15.0
Range (2; 73)
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SummarySummaryZarnestra in Zarnestra in Elderly Poor-Elderly Poor-
Risk AMLRisk AML
Durable CR : an endpoint supportive of Durable CR : an endpoint supportive of clinical benefit in AMLclinical benefit in AML
Consider in the context of :Consider in the context of : 11.1% CRR with 275 days median duration11.1% CRR with 275 days median duration Poor risk patient populationPoor risk patient population 12% one-month death rate12% one-month death rate 60% hospitalization60% hospitalization
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QuestionQuestion
Does the risk benefit analysis Does the risk benefit analysis support regular approval of support regular approval of Zarnestra for the first-line Zarnestra for the first-line treatment of AML patients treatment of AML patients age 65 or older with prior age 65 or older with prior MDS or age 75 and older?MDS or age 75 and older?
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Additional SlidesAdditional Slides
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SummarySummary
Standard Treatment Risk & Benefit Standard Treatment Risk & Benefit in general and in elderly poor-risk in general and in elderly poor-risk AML patients:AML patients:
Outcome versus Age < 65 >65 + Poor-risk
Treatment related death 10-20% > 25%
Complete remission rate 60-75% 30% - 50%
2 year survival rate 30-40% > 3 years < 6% at 2 year
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SummarySummary Zarnestra Risk & Benefit in elderly Zarnestra Risk & Benefit in elderly
poor-risk AML patients compare to poor-risk AML patients compare to and Standard Treatment in elderly and Standard Treatment in elderly AML patients:AML patients:
Outcome versus Tx Zarnestra Standard
Complete remission rate 11.1% 30% - 50%
Treatment related death 7% > 25%
One month mortality 12% 30- 48%
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Approvals for APL, MDSApprovals for APL, MDSDrug Indication Trial (s) Benefit
Tretinoin Second-line APL One single arm trial and two cohorts
73%-80% CR’s ; cohorts 36%-68% CR rates
Arsenic Trioxide
Second-line APL
Single arm study
CR = 70%
5-Azacytidine MDS BSC vs BSC+vidaza 2 single arm trials
CR+PR=16% vs 0% transfusion independence: AML subgroup N=10 in vidaza arm 12.5% CR CR+PR=14% and 19%: AML subgroup N=17 and N=1, combined CR=18%
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Unfavorable KaryotypeUnfavorable Karyotype
Per the sponsor, the Per the sponsor, the karyotypes described as karyotypes described as unfavorable included: unfavorable included: del 5, del 5q, del 5, del 5q, del 7, del 7q, del 7, del 7q, trisomy 8, trisomy 8, 11q23, 11q23, complex (> 3 abnormalities). complex (> 3 abnormalities).
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Summary of Patients Summary of Patients with or without Prior MDS with or without Prior MDS
Population< 65 years
n (%)65-74 years
n (%)75 years
n (%)Totaln (%)
All Treated AML 7/9 (78%) 61/73 (84%) 49/74 (66%)117/156
(75%)
Elderly Poor-Risk AML
0/061/61 (100%)
49/74 (66%)110/135
(81%)
Per Protocol 0/048/48 (100%)
41/55 (75%)89/103
(86%)
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Sponsor’s RR by Risk FactorsSponsor’s RR by Risk FactorsTotal CR PR
Age 136 20 (15) 3 (2)
65-74 y 61 11 (18) 3 (5)
> 75 y 75 9 (12) -
Karyotype unfavorable 136 20 (15) 3 (2)
Yes 66 9 (14) 3 (5)
No 62 10 (16) -
Not done / not available 8 1 (13) -
Organ dysfunction 136 20 (15) 3 (2)
Yes 83 13 (16) 2 (2)
No 53 7 (13) 1 (2)
Prior MDS 136 20 (15) 3 (2)
Yes 111 18 (16) 3 (3)
No 25 2 (8) -
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CTEP-20: Complete Remission CTEP-20: Complete Remission CriteriaCriteria
Bone marrow < 5% myeloblasts with Bone marrow < 5% myeloblasts with normal maturation of all cell lines, an ANC normal maturation of all cell lines, an ANC >> 1000/uL, a platelet 1000/uL, a platelet >> 100, 000/uL, 100, 000/uL, absence of blasts in peripheral blood, absence of blasts in peripheral blood, absence of identifiable leukemic cells in absence of identifiable leukemic cells in the bone marrow, clearance of disease-the bone marrow, clearance of disease-associated cytogenetic abnormalities, and associated cytogenetic abnormalities, and clearance of any previously existing clearance of any previously existing extramedullary disease. extramedullary disease.
CR must be confirmed 4-6 weeks after CR must be confirmed 4-6 weeks after initial documentation. At least one bone initial documentation. At least one bone marrow biopsy should be performed to marrow biopsy should be performed to confirm CR.confirm CR.
NCI-Sponsored Workshop on Definitions of Diagnosis and Response in Acute Myeloid Leukemia, 1990.NCI-Sponsored Workshop on Definitions of Diagnosis and Response in Acute Myeloid Leukemia, 1990.
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CTEP-20 Safety – Overall AEsCTEP-20 Safety – Overall AEsNumber (%) of Subjects With: Elderly Poor- Risk AML All- Treated
AML
65-74 y prior MDSN = 61 (%)
> 75 yN = 75 (%)
TotalN= 136 (%)
Total(N= 157) (%)
AEs 60 (98) 74 (99) 134 (99) 155 (99)
Drug-related AEs 53 (87) 65 (87) 118 (87) 134 (85)
Grade 3 or 4 AEs 51 (84) 62 (83) 113 (83) 131 (83)
Drug- related grade 3 or 4 AEs 37 (61) 46 (61) 83 (61) 92 (59)
SAEs 38 (62) 50 (67) 88 (65) 103 (66)
Drug- related SAEs 23 (38) 35 (47) 58 (43) 64 (41)
AEs leading to treatment termination
11 (18) 10 (13) 21 (15) 26 (17)
Drug- related AEs leading to treatment terminationa
7 (11) 7 (9) 14 (10) 18 (11)
Deaths due to an AE 2 (3) 7 (9) 9 (7) 11 (7)
Drug- related AEs resulting in death
0 1 (1) 1 (1) 1 (1)
Early deaths due to an AE 2 (3) 3 (4) 5 (4) 6 (4)
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CTEP-20 Safety –CTEP-20 Safety – Common Non Common Non Hem. AEsHem. AEs
WHO Preferred Term Total N= 136 (%)
Diarrhea 64 (47)
Fatigue 60 (44)
Nausea 51 (38)
Rash 48 (35)
Fever 42 (31)
Anorexia 37 (27)
Constipation 33 (24)
Vomiting 32 (24)
Dyspnea 32 (24)
Dizziness 36 (26)
Ataxia + abnormal gait 27 (20)
Confusion 29 (21)
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CTEP-20 Safety – Common Hem & CTEP-20 Safety – Common Hem & Met AEsMet AEs
WHO Preferred Term Total N= 136 (%)
Neutropenia febrile 40 (29)
Purpura 29 (21)
Thrombocytopenia 26 (19)
Anemia 24 (18)
Neutropenia 17 (13)
Infection bacterial 27 (20)
Moniliasis and other fungal infection 22 (16)
Creatinine 62 (46)
Hypokalemia 59 (43)
Hyponatremia 57 (42)
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CTEP-20 SafetyCTEP-20 Safety AEs Leading to Treatment AEs Leading to Treatment
TerminationTerminationWHO Preferred Term Total N= 136 (%)
All Drug Related
Total no. subjects with AE 21 (15) 14 (10)
Creatinine blood increased 4 (3) 3 (2)
Rash 4 (3) 3 (2)
Pancreas enzymes increased 2 (1) 2 (1)
Dehydration 1 (1) 1 (1)
Diarrhea 1 (1) 1 (1)
Dizziness 1 (1) 1 (1)
Fatigue 1 (1) 1 (1)
Insomnia 1 (1) 1 (1)
Nausea 1 (1) 1 (1)
Neuropathy peripheral 1 (1) 1 (1)
Sweating increased 1 (1) 1 (1)
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CTEP-20 SafetyCTEP-20 Safety – – AEs Leading to Dose Reduction (AEs Leading to Dose Reduction (>>
2%)2%)WHO Preferred Term Total (N= 136) (%)
All Drug Related
Total no. subjects with AE 47 (35) 35 (26)
Neutropenia febrile 9 (7) 6 (4)
Ataxia 5 (4) 5 (4)
Creatinine blood increased 6 (4) 4 (3)
Confusion 6 (4) 3 (2)
Diarrhea 4 (3) 3 (2)
Neutropenia 4 (3) 3 (2)
Pancreas enzymes increased 3 (2) 3 (2)
Rash 5 (4) 3 (2)
Renal function abnormal 3 (2) 3 (2)
Amnesia 2 (1) 2 (1)
Bilirubinemia 3 (2) 2 (1)
Fatigue 2 (1) 2 (1)
Hypotension postural 2 (1) 2 (1)
Infection bacterial 3 (2) 2 (1)
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CTEP-20 SafetyCTEP-20 Safety – – AEs Causing Treatment Interuption (AEs Causing Treatment Interuption (>>
2%)2%)WHO Preferred Term Total N= 136 (%)
All Drug Related
Total no. subjects with AE 56 (41) 45 (33)
Neutropenia 10 (7) 8 (6)
Creatinine blood increased 10 (7) 7 (5)
Nausea 6 (4) 6 (4)
Neutropenia febrile 8 (6) 6 (4)
Rash 5 (4) 5 (4)
Confusion 3 (2) 3 (2)
Pancytopenia 4 (3) 3 (2)
Vomiting 3 (2) 3 (2)
Ataxia 2 (1) 2 (1)
Bilirubinemia 3 (2) 2 (1)
Diarrhea 3 (2) 2 (1)
Gait abnormal 2 (1) 2 (1)
Infection bacterial 3 (2) 2 (1)
Infection fungal 2 (1) 2 (1)
Neuropathy peripheral 2 (1) 2 (1)
Pneumonia 4 (3) 2 (1)
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CTEP-20 Safety – ACTEP-20 Safety – AEs Associated with Es Associated with DeathDeath
WHO Preferred Term Total N= 136 (%)
Total no. subjects who died 9 (7)
Cardiac failure 3 (2)
Sepsis 3 (2)
Infection fungal 2 (1)
Pneumonia 2 (1)
Arrhythmia atrial 1 (1)
Circulatory failure 1 (1)
Fibrillation atrial 1 (1)
Gastrointestinal hemorrhage 1 (1)
Hypoxia 1 (1)
Multiple organ failure 1 (1)
Neutropenia febrile 1 (1)
Pulmonary hemorrhage 1 (1)
Renal failure acute 1 (1)
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CTEP-20: Concomitant Therapy During CTEP-20: Concomitant Therapy During TreatmentTreatment
Total N= 136 (%)
Blood product transfusions 119 (88)
Human RBCsa 114 (84)
Platelets, human blood 89 (65)
White blood cells 3 (2)
Anti-infectives 116 (85)
Antibiotics 111 (82)
Antivirals 71 (52)
Antifungals 51 (38)
Hydroxyurea 3 (2)
Growth factors 12 (9)
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CTEP-20 – Reason for Hospitalization CTEP-20 – Reason for Hospitalization
Reason for hospitalization, N = 136 (%)
No. of subjects with recorded reason 81 (59)
AE related to study medication 51 (38)
AE related to disease 33 (24)
Other reason 18 (13)
Chemotherapy 2 (1)
Transfusion 2 (1)
AE related to medication (not tipifarnib) 2 (1)
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Sponsor’s Response Rate in Sponsor’s Response Rate in Relapsed AMLRelapsed AML
INT-17 and CTEP-1 INT-17 and CTEP-1
Response INT-17 (N= 99)
CTEP -1 (N= 22)
CR 2 (2%) 2 (9%)
PR 6 (6%) 6 (27%)