Trial · NCT01713582
A Dose-finding Study of the Bromodomain (Brd) Inhibitor OTX015/ Birabresib (MK-8628) in Hematologic Malignancies (MK-8628-001)
NCT01713582, Phase 1, Completed, Oncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA); results first posted 2018-10-01
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ConductScience Library. A Dose-finding Study of the Bromodomain (Brd) Inhibitor OTX015/ Birabresib (MK-8628) in Hematologic Malignancies (MK-8628-001). Trials, record NCT01713582. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01713582
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Dose-finding Study of the Bromodomain (Brd) Inhibitor OTX015/ Birabresib (MK-8628) in Hematologic Malignancies (MK-8628-001)
- NCT number
- NCT01713582
- Status
- Completed
- Phases
- Phase 1
- Enrollment
- 141 participants, actual
- Lead sponsor
- Oncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Conditions
- Acute Myeloid Leukemia, Diffuse Large B-cell Lymphoma, Acute Lymphoblastic Leukemia, Multiple Myeloma
- Interventions
- OTX015/Birabresib
- First posted
- 2012-10-24
- Last updated
- 2021-01-26
- Other registries' IDs
- eudract:2012-003380-22
- Results first posted
- 2018-10-01
Source ClinicalTrials.gov
Registered outcomes10
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Number of Participants With Dose Limiting Toxicities (DLTs) | Cycle 1 (Up to 21 days) | A DLT was graded using the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.02 and defined as any of the following: grade 3 or 4 non-hematologic adverse events unless they were not optimally treated with supportive care; grade 3 or 4 asymptomatic laboratory abnormal values lasting \>7 days; prolonged grade 2 toxicity (lasting more than 2 weeks) leading to treatment interruption and/or dose reduction; pancytopenia with a hypocellular bone marrow and no marrow blasts lasting ≥6 weeks (AL participants); grade 3 neutropenia with fever or infection (OHM participants); grade 3 thrombocytopenia with bleeding (OHM participants); or grade 4 neutropenia or thrombocytopenia, regardless of symptoms and lasting ≥3 days (OHM participants). |
| Secondary | Number of Participants Who Experienced at Least One Adverse Event (AE) | Up to 40 days after last dose of study therapy (Up to 28 months) | AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. AEs were collected during the entire time frame of treatment plus up to 40 days of follow-up. |
| Secondary | Number of Participants Who Discontinued Study Therapy Due to AEs | From time of first dose of study therapy until the end of treatment (up to 26 months) | All participants who discontinued study therapy due to an AE at any time during treatment. |
| Secondary | Number of Participants Whose Best Response Was Partial Response (PR) or Complete Response (CR) | From time of first dose of study therapy until the end of treatment (up to 26 months) | Best response was determined from the start of treatment until disease progression, recurrence, or completion of 26 months of treatment. Partial and complete response was assessed by bone marrow aspiration (AL participants); or computed tomography scan, magnetic resonance imaging, positron emission tomography, or X-ray (OHM participants) using standard criteria. Acute leukemia participants were assessed based on the recommendations from the European LeukemiaNet Döhner 2010); lymphoma participants according to Cheson 2007; and MM participants according to Durie 2006. |
| Secondary | Maximum Concentration (Cmax) of MK-8628/OTX015 | Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position | Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24 hours (h) + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level. Blood samples for Cmax were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies. |
| Secondary | Time to Maximum Concentration (Tmax) of MK-8628/OTX015 | Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position | Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level. Blood samples for Tmax were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies. |
| Secondary | Apparent Terminal Half-Life (t1/2) of MK-8628/OTX015 | Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position | Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level. Blood samples for t1/2 were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies. |
| Secondary | Area Under the Concentration Time Curve of MK-8628/OTX015 From Time 0 to Infinity (AUC 0-inf) | Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position | Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level. Blood samples for AUC 0-first were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies. |
| Secondary | Apparent Total Body Clearance (CL/F) of MK-8628/OTX015 | cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position | Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level. Blood samples for CL/F were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies. |
| Secondary | Volume of Distribution at Steady State (Vz/F) of MK-8628/OTX015 | Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position | Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level. Blood samples for Vz/F were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies. |
Source ClinicalTrials.gov
Outcomes10
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Number of Participants With Dose Limiting Toxicities (DLTs) | Cycle 1 (Up to 21 days) | All participants who received at least 85% of the intended dose of study therapy during the first cycle (i.e. \>12 days at full dose for AL and \>18 days at full dose for other hematological malignancies) or discontinued from the study due to a DLT attributable to study therapy. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Participants Who Experienced at Least One Adverse Event (AE) | Up to 40 days after last dose of study therapy (Up to 28 months) | All participants who received at least one dose of study therapy. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Participants Who Discontinued Study Therapy Due to AEs | From time of first dose of study therapy until the end of treatment (up to 26 months) | All participants who received at least one dose of study therapy. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Participants Whose Best Response Was Partial Response (PR) or Complete Response (CR) | From time of first dose of study therapy until the end of treatment (up to 26 months) | All participants who received one dose of study therapy and had at least one available tumor assessment by the end of Cycle 2 or later or with earlier evidence of response or progression. | Participants | NUMBER |
| SECONDARY | Maximum Concentration (Cmax) of MK-8628/OTX015 | Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position | All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen. | ug/L | MEAN |
| SECONDARY | Time to Maximum Concentration (Tmax) of MK-8628/OTX015 | Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position | All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen. | Hours | MEAN |
| SECONDARY | Apparent Terminal Half-Life (t1/2) of MK-8628/OTX015 | Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position | All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen. | Hours | MEAN |
| SECONDARY | Area Under the Concentration Time Curve of MK-8628/OTX015 From Time 0 to Infinity (AUC 0-inf) | Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position | All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen. | hr*ng/mL | MEAN |
| SECONDARY | Apparent Total Body Clearance (CL/F) of MK-8628/OTX015 | cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position | All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen. | L/hour | MEAN |
| SECONDARY | Volume of Distribution at Steady State (Vz/F) of MK-8628/OTX015 | Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position | All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen. | Liters | MEAN |
Source ClinicalTrials.gov
Results by group138
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | AL 10 mg QD 14-21 | 0 | Participants | ||
| Number of Participants With Dose Limiting Toxicities (DLTs) | AL 20 mg QD 14-21 | 0 | Participants | ||
| Number of Participants With Dose Limiting Toxicities (DLTs) | AL 40 mg QD 14-21 | 0 | Participants | ||
| Number of Participants With Dose Limiting Toxicities (DLTs) | AL 20 mg BID 21-21 | 0 | Participants | ||
| Number of Participants With Dose Limiting Toxicities (DLTs) | AL 80 mg QD 14-21 | 0 | Participants | ||
| Number of Participants With Dose Limiting Toxicities (DLTs) | AL 40 mg BID 14-21 | 0 | Participants | ||
| Number of Participants With Dose Limiting Toxicities (DLTs) | AL 120 mg QD 14-21 | 0 | Participants | ||
| Number of Participants With Dose Limiting Toxicities (DLTs) | AL 120 mg QD 21-21 | 0 | Participants | ||
| Number of Participants With Dose Limiting Toxicities (DLTs) | AL 160 mg QD 14-21 | 2 | Participants | ||
| Number of Participants With Dose Limiting Toxicities (DLTs) | AML de Novo 80 mg QD 14-21 | 0 | Participants |
1 to 10 of 138Source ClinicalTrials.gov
See all 138 results by groupParticipant flow63
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | AL 10 mg QD 14-21 | 3 | |
| Overall Study | STARTED | AL 20 mg QD 14-21 | 3 | |
| Overall Study | STARTED | AL 40 mg QD 14-21 | 4 | |
| Overall Study | STARTED | AL 20 mg BID 21-21 | 3 | |
| Overall Study | STARTED | AL 80 mg QD 14-21 | 4 | |
| Overall Study | STARTED | AL 40 mg BID 14-21 | 8 | |
| Overall Study | STARTED | AL 120 mg QD 14-21 | 7 | |
| Overall Study | STARTED | AL 120 mg QD 21-21 | 6 | |
| Overall Study | STARTED | AL 160 mg QD 14-21 | 6 | |
| Overall Study | STARTED | AML de Novo 80 mg QD 14-21 | 18 |
1 to 10 of 63Source ClinicalTrials.gov
See all 63 participant flowAdverse events8,505
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | AL 10 mg QD 14-21 | 2 | 3 | |
| other | Anaemia | Blood and lymphatic system disorders | AL 20 mg QD 14-21 | 2 | 3 | |
| other | Anaemia | Blood and lymphatic system disorders | AL 40 mg QD 14-21 | 3 | 4 | |
| other | Anaemia | Blood and lymphatic system disorders | AL 20 mg BID 21-21 | 1 | 3 | |
| other | Anaemia | Blood and lymphatic system disorders | AL 80 mg QD 14-21 | 4 | 4 | |
| other | Anaemia | Blood and lymphatic system disorders | AL 40 mg BID 14-21 | 7 | 8 | |
| other | Anaemia | Blood and lymphatic system disorders | AL 120 mg QD 14-21 | 5 | 7 | |
| other | Anaemia | Blood and lymphatic system disorders | AL 120 mg QD 21-21 | 5 | 6 | |
| other | Anaemia | Blood and lymphatic system disorders | AL 160 mg QD 14-21 | 3 | 6 | |
| other | Anaemia | Blood and lymphatic system disorders | AML de Novo 80 mg QD 14-21 | 9 | 18 |
1 to 10 of 8,505Source ClinicalTrials.gov
See all 8,505 adverse eventsAdverse event totals63
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | AL 10 mg QD 14-21 | 3 | 3 |
| Total, all-cause mortality | AL 20 mg QD 14-21 | 3 | 3 |
| Total, all-cause mortality | AL 40 mg QD 14-21 | 4 | 4 |
| Total, all-cause mortality | AL 20 mg BID 21-21 | 3 | 3 |
| Total, all-cause mortality | AL 80 mg QD 14-21 | 4 | 4 |
| Total, all-cause mortality | AL 40 mg BID 14-21 | 7 | 8 |
| Total, all-cause mortality | AL 120 mg QD 14-21 | 7 | 7 |
| Total, all-cause mortality | AL 120 mg QD 21-21 | 6 | 6 |
| Total, all-cause mortality | AL 160 mg QD 14-21 | 6 | 6 |
| Total, all-cause mortality | AML de Novo 80 mg QD 14-21 | 15 | 18 |
1 to 10 of 63Source ClinicalTrials.gov
See all 63 adverse event totalsPapers3
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT01713582
GET https://conductscience.org/api/trials/v1/NCT01713582/results?page=2