Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Decitabine

Antimetabolites

Enzyme Inhibitors

BI 836858

Boehringer Ingelheim

Phase I Dose Escalation:

Primary objective is to determine the Maximum Tolerated Dose (MTD) and the recommended dose for Phase I Extension.

Secondary objective is to investigate the safety, pharmacokinetics and efficacy of BI 836858 in combination with decitabine

Phase I Extension:

Primary objective is to collect additional data on safety, pharmacokinetics and efficacy and to define the Recommended Phase II Dose (RP2D) of BI 836858 in combination with decitabine.

Phase II: Primary objective is to investigate efficacy, safety and pharmacokinetics of BI 836858 in combination with decitabine compared to decitabine monotherapy.

Phase I Dose Escalation: Open-label, single-arm, dose escalation

- To determine the maximum tolerated dose (MTD) and the recommended dose for Phase I Extension (RExP1D)

Phase I Extension: Open-label, two consecutive groups (cohort A and B) - To collect additional data on safety, pharmacokinetics and efficacy and to decide if the RExP1D will become the Recommended Phase II Dose (RP2D)

Phase II: Open-label, two-arm randomized

- To investigate efficacy, safety and pharmacokinetics of BI 836858 in combination with decitabine compared to decitabine monotherapy

A Trial to Find and Investigate a Safe Dose of BI 836858 in Combination With Decitabine for Patients With Acute Myeloid Leukemia (AML)

An Open-label, Phase I/II Trial to Determine the Maximum Tolerated Dose and Investigate Safety, Pharmacokinetics and Efficacy of BI 836858 in Combination With Decitabine in Patients With Acute Myeloid Leukemia

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datasharing

Number of patients with dose limiting toxicity (DLT(s)) for BI 836858 in combination with decitabine during first treatment cycle (Phase 1).

DLT was defined as any non-disease-related non-haematological adverse event (AE) of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher. Expected non-haematological disease-related AEs were not to be regarded as a DLT.

These included complications resulting from haematological AEs such as:

* Bleeding and complications from bleeding due to thrombocytopenia as defined by the Investigator,
* Infection and complications from infections due to neutropenia as defined by the Investigator,
* Constitutional symptoms due to anaemia as defined by the Investigator

The Maximum tolerated dose (MTD) of BI 836858 in combination with decitabine was estimated after the dose escalation part of the trial obtaining on the basis of dose limiting toxicities (DLT(s)) observed during the first treatment cycle. However, for those patients who receive more than one cycle of the combination treatment, all adverse events that constitute a DLT will be considered for re-estimation of the MTD based on the Bayesian logistic regression model (BLRM). The MTD is defined as the highest dose of BI 836858 (in combination with decitabine) with less than 25% risk of the true DLT rate being above 33% during the MTD evaluation period.

Number of patients with objective response (Complete remission (CR) + complete remission with incomplete remission (CRi)).

CR was defined as bone marrow (BM) blasts \< 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \> 1.0 x 109/L \[1,000/μL\]; platelet count \> 100 x 109/L \[100,000/μL\]; independence of red blood cells transfusions (no transfusion for 1 week prior to the assessment). No minimum duration of response is required.

CRi was defined as all CR criteria except for residual neutropenia (\< 1.0 x 109/L \[1,000/μL\]) or thrombocytopenia (\< 100 x 109/L \[100,000/μL\]).

Treated set: All subjects who were documented to have received at least one dose of trial medication.

20 milligram (mg) of concentrate for solution for infusion of BI 836858 were administered as single dose via rate-controlled intravenous infusion once per week in 28-day treatment cycle (i.e. on Days 1, 8, 15, and 22 of the 28-day treatment cycles), together with 20 mg/square meter (m2) body surface area (BSA) of decitabine administered daily via intravenous infusion for 10 consecutive days (intensive treatment) from Day 1 to 10 in each treatment cycle. The BI 836858 dose was diluted in 0.9% sodium chloride to have full volume of the diluted compound 250 milliliter (mL).

Phase I Dose Escalation: BI 836858 20 mg + Decitabine (Intensive)

40 milligram (mg) of concentrate for solution for infusion of BI 836858 were administered as single dose via rate-controlled intravenous infusion once per week in 28-day treatment cycle (i.e. on Days 1, 8, 15, and 22 of the 28-day treatment cycles), together with 20 mg/square meter (m2) body surface area (BSA) of decitabine administered daily via intravenous infusion for 10 consecutive days (intensive treatment) from Day 1 to 10 in each treatment cycle. The BI 836858 dose was diluted in 0.9% sodium chloride to have full volume of the diluted compound 250 milliliter (mL).

Phase I Dose Escalation: BI 836858 40 mg + Decitabine (Intensive)

80 milligram (mg) of concentrate for solution for infusion of BI 836858 were administered as single dose via rate-controlled intravenous infusion once per week in 28-day treatment cycle (i.e. on Days 1, 8, 15, and 22 of the 28-day treatment cycles), together with 20 mg/square meter (m2) body surface area (BSA) of decitabine administered daily via intravenous infusion for 10 consecutive days (intensive treatment) from Day 1 to 10 in each treatment cycle. The BI 836858 dose was diluted in 0.9% sodium chloride to have full volume of the diluted compound 250 milliliter (mL).

Phase I Dose Escalation: BI 836858 80 mg + Decitabine (Intensive)

Phase I Extension A: BI 836858 80 mg + Decitabine (Intensive)

80 milligram (mg) of concentrate for solution for infusion of BI 836858 were administered as single dose via rate-controlled intravenous infusion once per week in 28-day treatment cycle (i.e. on Days 1, 8, 15, and 22 of the 28-day treatment cycles), together with 20 mg/square meter (m2) body surface area (BSA) of decitabine administered daily via intravenous infusion for 5 consecutive days (standard treatment) from Day 1 to 5 in each treatment cycle. The BI 836858 dose was diluted in 0.9% sodium chloride to have full volume of the diluted compound 250 milliliter (mL).

Phase I Extension B: BI 836858 80 mg + Decitabine (Standard)

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Treated set: The treated set includes all patients who have received at least one dose of study medication (BI 836858 and/or decitabine).

Sponsor stopped development of the study drug before Phase II start. Phase II was not performed.

Boehringer Ingelheim Call Center

Bayesian logistic regression model (BLRM) with overdose control was used to determine the maximum tolerated dose (MTD), defined as highest dose with less than 25% risk of the true DLT rate being equal to or above 33%.

Phase I: Number of Patients With Dose Limiting Toxicity (DLT(s)) During First Treatment Cycle

Comprises all dose cohorts during the Phase I dose escalation and extension parts. 20/40/80 milligram (mg) of BI 836858 were administered as single dose via rate-controlled intravenous infusion once per week in 28-day treatment cycle (i.e. on Days 1, 8, 15, and 22 of the 28-day treatment cycles), together with 20 mg/square meter (m2) body surface area (BSA) of decitabine administered daily via intravenous infusion for 10 consecutive days (intensive treatment) from Day 1 to 10 (standard treatment: 5 consecutive days from Day 1 to 5) in each treatment cycle. The BI 836858 dose was diluted in 0.9% sodium chloride to have full volume of the diluted compound 250 milliliter (mL).

Phase I: BI 836858 + Decitabine

Maximum Tolerated Dose (MTD) evaluable set: This analysis set includes all subjects who were entered, treated and completed first cycle of planned treatment or subjects received at least 2 doses of BI 836858 due to BI 836858-related toxicity but not replaced.

Spots Global Cancer Trial Database for A Trial to Find and Investigate a Safe Dose of BI 836858 in Combination With Decitabine for Patients With Acute Myeloid Leukemia (AML)

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