Phase 2
N=68
BI 811283 in Combination With Cytarabine in Previously Untreated AML Ineligible for Intensive Treatment
Leukemia, Myeloid, Acute
Bottom Line
View on ClinicalTrials.gov: NCT00632749 ↗Enrolled (actual)
68
Serious AEs
89.1%
Results posted
May 2015
Primary outcome: Primary: The Maximum Tolerated Dose (MTD) of 2 Schedules of BI 811283 in Combination With Cytarabine. — 100; NA mg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- BI 811283 (d 1 and 15) (Drug); Cytarabine (Drug); BI 811283 (d1) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Boehringer Ingelheim
- Primary completion
- Mar 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Maximum Tolerated Dose (MTD) of 2 Schedules of BI 811283 in Combination With Cytarabine. |
100; NA | — |
| SECONDARY Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) |
0; 0; 0; 1; 0; 1 | — |
| SECONDARY Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Incidence of Dose Limiting Toxicity (DLT) |
0; 0; 0; 0; 0; 2 | — |
| SECONDARY Partial Remission |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Event Free Survival (EFS) |
35.0; 122.3; 32.0; 117.5; 60.4; 62.0 | — |
| SECONDARY Relapse Free Survival |
1; 1; 1; 1; 1; 1 | — |
| SECONDARY Remission Duration |
263.0; 28.0; 337.0; 455.0; 128.0; 15.0 | — |
| SECONDARY Overall Survival (OS) |
122.8; 212.0; 71.3; 236.8; 148.7; 86.6 | — |
| SECONDARY Cmax (Maximum Measured Concentration of BI 811283 in Plasma) |
8.03; 64.10; 104.00; 153.00; 214.00; 272.00 | — |
| SECONDARY AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) |
177; 985; 1000; 2790; 4400; 5620 | — |
| SECONDARY AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) |
169; 939; 2010; 2350; 2810; 5340 | — |
| SECONDARY Cmax,ss (Maximum Measured Concentration of BI 811283 in Plasma at Steady State) |
8.02; 24.7; 43.3; 141; 213; 229 | — |
| SECONDARY AUC (0-inf, ss)(Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) at Steady State |
188; 615; NA; 4460; 5140; 4750 | — |
| SECONDARY AUC (0-tz,ss) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) at Steady State |
183; 597; 1620; 4330; 4340; 4820 | — |
| SECONDARY Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) |
24.0; 26.0; 25.0; 22.7; 6.0; 23.6 | — |
| SECONDARY Tmax,ss (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma at Steady State) |
23.9; 24.0; 6.0; 6.0; 6.0; 6.0 | — |
| SECONDARY Cmax (Maximum Measured Concentration of Cytarabine in Plasma) |
53.2; 72.6; 49.0; 64.9; 61.9; 46.0 | — |
| SECONDARY Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) |
0.50; 0.50; 0.92; 0.83; 0.48; 0.55 | — |
| SECONDARY AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) |
104; 122; 102; 85.4; 65.9; 68.1 | — |
| SECONDARY AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) |
45.0; 66.9; 66.8; 71.8; 46.6; 42.3 | — |
| SECONDARY Pharmacodynamic Monitoring |
— | — |
| SECONDARY Pharmacokinetics of Cytarabine After a Single Dose and at Steady State When Given Alone |
— | — |
Summary
Investigation of maximum tolerated dose, safety, efficacy and pharmcokinetics of BI 811283 in combination with cytarabine (LD-Ara-C) in previously untreated acute myeloid leukaemia (AML) patients
Eligibility Criteria
Inclusion criteria
- Male or female adult with previously untreated acute myeloid leukaemia (AML)
- Confirmed diagnosis of AML according to the WHO definition (except for acute promyelocytic leukaemia, APL)
- Patient is considered ineligible for intensive treatment
- Patient is eligible for low-dose cytarabine (LD-Ara-C) treatment
- Life expectancy > 3 months
- Eastern co-operative oncology group (ECOG, R01-0787) performance score 1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin).
- Bilirubin greater than 1.5 mg/dl.
- Serum creatinine greater than 2.0 mg/dl.
- LVEF (Left ventricular ejection fraction) < 50% in echocardiography or clinical congestive heart failure New York Heart Association (NYHA) grade III or IV.
- Concomitant intercurrent illness, which would compromise the evaluation of efficacy or safety of the trial drug, e.g. active severe infection, unstable angina pectoris or cardiac arrhythmia.
- Psychiatric illness or social situation that would limit compliance with trial requirements.
- Concomitant therapy, which is considered relevant for the evaluation of the efficacy or safety of the trial drug (i.e. other chemo- or immunotherapy, see also section 4.2.2).
- Contraindications for cytarabine treatment according to the summary of product characteristics (SPC).
- Patients who are sexually active and unwilling to use a medically acceptable method of contraception during the trial (hormonal contraception, intrauterine device, condom with spermicide, etc.).
- Pregnant or nursing female patients.
- Patient unable to comply with the protocol.
Data sourced from ClinicalTrials.gov (NCT00632749). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.