Back to resultsStudy of Bromodomain and Extra-Terminal Protein (BET) Inhibitor RO6870810 as Mono- and Combination Therapy in Advanced Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
RO6870810
daratumumab
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Performance status </=2 on the Eastern Cooperative Oncology Group (ECOG) scale
- Life expectancy > 3 months
- Relapsed or refractory multiple myeloma. Participants with primary refractory myeloma only allowed in dose-escalation phase of the study.
- Prior treatment: Treated with at least three prior lines of multiple myeloma therapy including a proteasome inhibitor and an immuno modulatory agent or who are double refractory to a proteasome inhibitor and an immuno modulatory agent. Prior anti-CD38 antibody (e.g., daratumumab, isatuximab) treatment is acceptable only for participants receiving monotherapy treatment.
- Prior treatment: Treated with two or more lines of prior therapy, with disease refractory to both a proteasome inhibitor and an immunomodulatory agent, and disease progression (as defined by International Myeloma Working Group (IMWG) criteria) following treatment with an anti-CD38 monoclonal antibody given as monotherapy or in combination therapy. The most recent treatment regimen must have contained an anti-CD38 monoclonal antibody.
- Treatment with prior autologous transplant is permitted
- Documented diagnosis of symptomatic multiple myeloma, as defined by the IMWG
- Measurable disease defined as at least one of the following: serum M-protein >/=1 grams/deciliter (g/dL), urine M-protein >/= 200 milligrams/24 hours (mg/24h), serum free light chain (SFLC) assay: involved SFLCs >/= 10 mg/dL (>/= 100 mg/L) and an abnormal SFLC ratio (<0.26 or >1.65).
- Female participants of childbearing potential must have a negative serum pregnancy test within the 7 days prior to the first study drug administration.
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 2 months after the last dose of RO6870810 as monotherapy, or for at least 3 months after the last dose of daratumumab.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 4 months after the last dose of RO6870810 as monotherapy, or for at least 3 months after the last dose of daratumumab.
Exclusion Criteria:
- Plasma cell leukemia defined as peripheral plasma cell count > 2000/cubic millimeter (mm^3)
- For expansion cohorts only: Primary refractory multiple myeloma defined as disease that is non-responsive in participants who have never achieved a minimal response or better with any therapy
- History of other malignancy within 2 years prior to screening, except for ductal carcinoma in situ not requiring chemotherapy, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, low-grade, localized prostate cancer (Gleason score </= 7) not requiring treatment or appropriately treated Stage I uterine cancer
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
- Current or prior disease or treatment that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor
- Pregnant or breastfeeding female.
- Consumption of agents which strongly inhibit CYP3A4 enzyme, within 7 days prior to the first dose of study treatment and during the study.
- Consumption of agents which strongly induce CYP3A4 enzyme, within 14 days prior to the first dose of study treatment and during the study.
- Surgery within 21 days prior to study entry.
- Prior treatment with small molecule BET family inhibitor or receiving steroids >the equivalent of 10mg prednisone daily
- participants who are currently receiving any other investigational agent or have received an investigational agent within 30 days or 5 half-lives, whichever is longer, prior to study entry
- Uncontrolled cancer pain
- Prior anti-cancer therapy (chemotherapy, targeted agents, radiotherapy, and immunotherapy) within 14 days except for alkylating agents (e.g., melphalan) within 28 days.
Sites / Locations
- City of Hope
- Stanford Cancer Center
- Mayo Clinic
- Emory Uni - Winship Cancer Center; Hematology/Oncology
- Dana Farber Cancer Institute
- Mount Sinai - PRIME; Icahn School of Medicine at Mount Sinai
- University of North Carolina at Chapel Hill
- Duke Clin Rsch Institute
- Scientia Clinical Research Limited
- St Vincent's Hospital Melbourne
- University College London Hospitals; Clinical Research Facility
- Oxford University Hospitals NHS Trust; Churchill Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
RO6870810
RO6870810 + Daratumumab
Arm Description
Participants will be administered RO6870810 monotherapy at ascending-dose levels during the dose escalation phase followed by an expansion phase during which RO6870810 will be administered as monotherapy at the recommended dose. Participants will continue to receive study drug as long as they experience clinical benefit in the opinion of the Investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression, as determined by the Investigator after an integrated assessment of IMWG response criteria, biopsies/aspirate (if applicable), and clinical status, or withdrawal of consent.
Participants will be administered RO6870810 at ascending-dose levels in combination with daratumumab at the recommended dose during the dose escalation phase followed by an expansion phase during which both RO6870810 and daratumumab will be administered each at their recommended dose. Participants will continue to receive the study drugs as long as they experience clinical benefit in the opinion of the Investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression, as determined by the Investigator after an integrated assessment of IMWG response criteria, biopsies/aspirate (if applicable), and clinical status, or withdrawal of consent.
Outcomes
Primary Outcome Measures
Number of Dose-Limiting Toxicities (DLTs)
DLTs are defined as the toxicities known and expected of RO6870810 and daratumumab that occur during a DLT assessment window of 21 days from the first administration of RO6870810 or study combination treatments, and are considered by the Investigator to be related to study treatment. DLTs are defined at specific severity levels for each term and include, but are not limited to the following Common Terminology Criteria for Adverse Events (CTCAE) terms: neutropenia, febrile neutropenia, thrombocytopenia, anemia and injection site reaction.
Objective Response Rate (ORR)
ORR is defined as the percentage of participants whose confirmed best overall response is either complete response (CR, including stringent complete response [sCR]) or partial response (PR, including very good partial response [VGPR]), assessed with use of the IMWG criteria. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow aspirates. sCR: CR plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. PR: >/=50% reduction of serum M-protein plus reduction in 24h urinary M-protein by >/=90% or to <200 mg/24h. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis; or >/=90% reduction in serum M-protein plus urine M-protein level <100 mg/24h. ORR= CR + sCR + PR + VGPR
Progression Free Survival (PFS)
PFS is defined as the time from first study treatment to the first occurrence of disease progression (per IMWG criteria) or death, whichever occurs first. Disease progression is defined as an increase of >/= 25% from lowest response value in any one or more of the following: serum M-component, urine M-component, in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (the absolute increase must be >10 mg/dL), bone marrow plasma cell percentage (absolute level >/= 10%), definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas, development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
Duration of Response (DoR)
DoR is defined as the time from the first occurrence of a documented objective response (sCR, CR, VGPR, or PR) to the time of first disease progression per IMWG criteria or death from any cause, whichever occurs first. Disease progression is defined as an increase of >/= 25% from lowest response value in any one or more of the following: serum M-component, urine M-component, in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (the absolute increase must be >10 mg/dL), bone marrow plasma cell percentage (absolute level >/= 10%), definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas, development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
Overall survival (OS)
OS is defined as the time from study enrollment until death from any cause.
Secondary Outcome Measures
Percentage of Participants with Adverse Events
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Maximum Observed Plasma Concentration (Cmax) of RO6870810
Maximum observed concentration of RO6870810 as determined by measuring drug concentration in blood samples over time.
Time to Reach Maximum Observed Plasma Concentration (tmax) of RO6870810
Time from dose administration to observed maximum serum concentration for RO6870810 as determined by measuring drug concentration in blood samples over time.
Apparent Plasma Clearance (CL/F) of RO6870810
Apparent clearance (CL/F) of RO6870810, where CL is clearance and F is bioavailability (relative amount of extravascularly-administered drug that reaches systemic circulation unchanged). Determined by measuring drug concentration in blood samples over time.
Apparent Volume of Distribution (V/F) of RO6870810
Apparent volume of distribution (V/F) for RO6870810, where V is the volume of distribution and F is bioavailability (relative amount of extravascularly-administered drug that reaches systemic circulation unchanged). Determined by measuring drug concentration in blood samples over time.
Area Under the Plasma Concentration-Time Curve (AUC) of RO6870810
AUC for RO6870810 describes the extent of absorption from time of dose administration to time of sampling as determined by measuring drug concentration in blood samples over time.
Half-life (t1/2) of RO6870810
Half-life of RO6870810 is the time elapsed for the drug concentration to decrease by half as determined by measuring drug concentration in blood samples over time.
Renal Clearance (CLr) of RO6870810
Clearance of RO6870810 through the kidneys as determined by measuring drug concentration in urine samples over time.
M-Protein Levels
M-protein levels pre- and post-treatment will be monitored as a measure of biological response.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03068351
Brief Title
Study of Bromodomain and Extra-Terminal Protein (BET) Inhibitor RO6870810 as Mono- and Combination Therapy in Advanced Multiple Myeloma
Official Title
Open-label, Multicenter, Dose-escalation/Expansion Phase Ib Study to Evaluate Safety, Pharmacokinetics, and Activity of BET Inhibitor RO6870810, Given as Mono- and Combination Therapy to Patients With Advanced Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
June 26, 2017 (Actual)
Primary Completion Date
August 1, 2019 (Actual)
Study Completion Date
August 1, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase Ib, open-label, multicenter, global study designed to assess the safety and tolerability of RO6870810 as monotherapy and in combination with daratumumab in participants with relapsed/refractory multiple myeloma. Each treatment cycle will be 21 days in length. There are two parts to this study. A dose-escalation phase (Part I) will be used to evaluate the safety and tolerability and dose limiting toxicities, and to establish the maximum tolerated dose (MTR)/optimum biological dose (OBD) of RO6870810 when given as monotherapy or in combination with daratumumab. A dose-expansion phase (Part II) will further characterize the safety, tolerability and activity of RO6870810 as monotherapy or in combination with daratumumab at the defined expansion dose-levels.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RO6870810
Arm Type
Experimental
Arm Description
Participants will be administered RO6870810 monotherapy at ascending-dose levels during the dose escalation phase followed by an expansion phase during which RO6870810 will be administered as monotherapy at the recommended dose. Participants will continue to receive study drug as long as they experience clinical benefit in the opinion of the Investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression, as determined by the Investigator after an integrated assessment of IMWG response criteria, biopsies/aspirate (if applicable), and clinical status, or withdrawal of consent.
Arm Title
RO6870810 + Daratumumab
Arm Type
Experimental
Arm Description
Participants will be administered RO6870810 at ascending-dose levels in combination with daratumumab at the recommended dose during the dose escalation phase followed by an expansion phase during which both RO6870810 and daratumumab will be administered each at their recommended dose. Participants will continue to receive the study drugs as long as they experience clinical benefit in the opinion of the Investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression, as determined by the Investigator after an integrated assessment of IMWG response criteria, biopsies/aspirate (if applicable), and clinical status, or withdrawal of consent.
Intervention Type
Drug
Intervention Name(s)
RO6870810
Intervention Description
RO6870810 will be administered subcutaneously (SC) at ascending-dose levels (from 0.30 milligrams/kilogram [mg/kg] to 0.65 mg/kg). In Cycle 1, RO6870810 will be given on Day 1 (omitted on Day 2) and then every day from Day 3 through to Day 15. Starting at Cycle 2, it will be given every day from Day 1 to Day 14 of each 21-day cycle. In the first combination therapy cohort RO6870810 will be administered at one dose-level below the maximum tolerated dose (MTD).
Intervention Type
Biological
Intervention Name(s)
daratumumab
Intervention Description
Daratumumab will be administered intravenously (IV) at a dose of 16 milligrams/kilogram (mg/kg) of body weight weekly for the first 8 weeks, every two weeks for the following 16 weeks, and every four weeks thereafter, until disease progression.
Primary Outcome Measure Information:
Title
Number of Dose-Limiting Toxicities (DLTs)
Description
DLTs are defined as the toxicities known and expected of RO6870810 and daratumumab that occur during a DLT assessment window of 21 days from the first administration of RO6870810 or study combination treatments, and are considered by the Investigator to be related to study treatment. DLTs are defined at specific severity levels for each term and include, but are not limited to the following Common Terminology Criteria for Adverse Events (CTCAE) terms: neutropenia, febrile neutropenia, thrombocytopenia, anemia and injection site reaction.
Time Frame
From first drug administration to end of dose-escalation phase (up to approximately 1 year)
Title
Objective Response Rate (ORR)
Description
ORR is defined as the percentage of participants whose confirmed best overall response is either complete response (CR, including stringent complete response [sCR]) or partial response (PR, including very good partial response [VGPR]), assessed with use of the IMWG criteria. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow aspirates. sCR: CR plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. PR: >/=50% reduction of serum M-protein plus reduction in 24h urinary M-protein by >/=90% or to <200 mg/24h. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis; or >/=90% reduction in serum M-protein plus urine M-protein level <100 mg/24h. ORR= CR + sCR + PR + VGPR
Time Frame
From baseline to end of study (up to approximately 2.5 years)
Title
Progression Free Survival (PFS)
Description
PFS is defined as the time from first study treatment to the first occurrence of disease progression (per IMWG criteria) or death, whichever occurs first. Disease progression is defined as an increase of >/= 25% from lowest response value in any one or more of the following: serum M-component, urine M-component, in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (the absolute increase must be >10 mg/dL), bone marrow plasma cell percentage (absolute level >/= 10%), definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas, development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
Time Frame
From baseline to end of study (up to approximately 2.5 years)
Title
Duration of Response (DoR)
Description
DoR is defined as the time from the first occurrence of a documented objective response (sCR, CR, VGPR, or PR) to the time of first disease progression per IMWG criteria or death from any cause, whichever occurs first. Disease progression is defined as an increase of >/= 25% from lowest response value in any one or more of the following: serum M-component, urine M-component, in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (the absolute increase must be >10 mg/dL), bone marrow plasma cell percentage (absolute level >/= 10%), definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas, development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
Time Frame
From baseline to end of study (up to approximately 2.5 years)
Title
Overall survival (OS)
Description
OS is defined as the time from study enrollment until death from any cause.
Time Frame
From baseline to end of study (up to approximately 2.5 years)
Secondary Outcome Measure Information:
Title
Percentage of Participants with Adverse Events
Description
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame
From baseline to end of study (up to approximately 2.5 years)
Title
Maximum Observed Plasma Concentration (Cmax) of RO6870810
Description
Maximum observed concentration of RO6870810 as determined by measuring drug concentration in blood samples over time.
Time Frame
Cycle 1, Days 1 and 15: predose, 0.25 hours (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 24 h, 48 h; Cycle 1, Day 8 predose; all subsequent cycles predose on Day 1 and at end of treatment (EOT- up to approximately 2.5 years)
Title
Time to Reach Maximum Observed Plasma Concentration (tmax) of RO6870810
Description
Time from dose administration to observed maximum serum concentration for RO6870810 as determined by measuring drug concentration in blood samples over time.
Time Frame
Cycle 1, Days 1 and 15: predose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 24 h, 48 h; Cycle 1, Day 8 predose; all subsequent cycles predose on Day 1 and at end of treatment (EOT - up to approximately 2.5 years)
Title
Apparent Plasma Clearance (CL/F) of RO6870810
Description
Apparent clearance (CL/F) of RO6870810, where CL is clearance and F is bioavailability (relative amount of extravascularly-administered drug that reaches systemic circulation unchanged). Determined by measuring drug concentration in blood samples over time.
Time Frame
Cycle 1, Days 1 and 15: predose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 24 h, 48 h; Cycle 1, Day 8 predose; all subsequent cycles predose on Day 1 and at end of treatment (EOT - up to approximately 2.5 years)
Title
Apparent Volume of Distribution (V/F) of RO6870810
Description
Apparent volume of distribution (V/F) for RO6870810, where V is the volume of distribution and F is bioavailability (relative amount of extravascularly-administered drug that reaches systemic circulation unchanged). Determined by measuring drug concentration in blood samples over time.
Time Frame
Cycle 1, Days 1 and 15: predose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 24 h, 48 h; Cycle 1, Day 8 predose; all subsequent cycles predose on Day 1 and at end of treatment (EOT - up to approximately 2.5 years)
Title
Area Under the Plasma Concentration-Time Curve (AUC) of RO6870810
Description
AUC for RO6870810 describes the extent of absorption from time of dose administration to time of sampling as determined by measuring drug concentration in blood samples over time.
Time Frame
Cycle 1, Days 1 and 15: predose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 24 h, 48 h; Cycle 1, Day 8 predose; all subsequent cycles predose on Day 1 and at end of treatment (EOT - up to approximately 2.5 years)
Title
Half-life (t1/2) of RO6870810
Description
Half-life of RO6870810 is the time elapsed for the drug concentration to decrease by half as determined by measuring drug concentration in blood samples over time.
Time Frame
Cycle 1, Days 1 and 15: predose, 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 24 h, 48 h; Cycle 1, Day 8 predose; all subsequent cycles predose on Day 1 and at end of treatment (EOT - up to approximately 2.5 years)
Title
Renal Clearance (CLr) of RO6870810
Description
Clearance of RO6870810 through the kidneys as determined by measuring drug concentration in urine samples over time.
Time Frame
Cycle 1, Day 1: predose, 0-1 h, 1-4 h, 4-8 h; Cycle 1, Day 15: predose, 0 h, 2 h, 6 h
Title
M-Protein Levels
Description
M-protein levels pre- and post-treatment will be monitored as a measure of biological response.
Time Frame
At baseline, end of study (up to approximately 2.5 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Performance status </=2 on the Eastern Cooperative Oncology Group (ECOG) scale
Life expectancy > 3 months
Relapsed or refractory multiple myeloma. Participants with primary refractory myeloma only allowed in dose-escalation phase of the study.
Prior treatment: Treated with at least three prior lines of multiple myeloma therapy including a proteasome inhibitor and an immuno modulatory agent or who are double refractory to a proteasome inhibitor and an immuno modulatory agent. Prior anti-CD38 antibody (e.g., daratumumab, isatuximab) treatment is acceptable only for participants receiving monotherapy treatment.
Prior treatment: Treated with two or more lines of prior therapy, with disease refractory to both a proteasome inhibitor and an immunomodulatory agent, and disease progression (as defined by International Myeloma Working Group (IMWG) criteria) following treatment with an anti-CD38 monoclonal antibody given as monotherapy or in combination therapy. The most recent treatment regimen must have contained an anti-CD38 monoclonal antibody.
Treatment with prior autologous transplant is permitted
Documented diagnosis of symptomatic multiple myeloma, as defined by the IMWG
Measurable disease defined as at least one of the following: serum M-protein >/=1 grams/deciliter (g/dL), urine M-protein >/= 200 milligrams/24 hours (mg/24h), serum free light chain (SFLC) assay: involved SFLCs >/= 10 mg/dL (>/= 100 mg/L) and an abnormal SFLC ratio (<0.26 or >1.65).
Female participants of childbearing potential must have a negative serum pregnancy test within the 7 days prior to the first study drug administration.
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 2 months after the last dose of RO6870810 as monotherapy, or for at least 3 months after the last dose of daratumumab.
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 4 months after the last dose of RO6870810 as monotherapy, or for at least 3 months after the last dose of daratumumab.
Exclusion Criteria:
Plasma cell leukemia defined as peripheral plasma cell count > 2000/cubic millimeter (mm^3)
For expansion cohorts only: Primary refractory multiple myeloma defined as disease that is non-responsive in participants who have never achieved a minimal response or better with any therapy
History of other malignancy within 2 years prior to screening, except for ductal carcinoma in situ not requiring chemotherapy, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, low-grade, localized prostate cancer (Gleason score </= 7) not requiring treatment or appropriately treated Stage I uterine cancer
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
Current or prior disease or treatment that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor
Pregnant or breastfeeding female.
Consumption of agents which strongly inhibit CYP3A4 enzyme, within 7 days prior to the first dose of study treatment and during the study.
Consumption of agents which strongly induce CYP3A4 enzyme, within 14 days prior to the first dose of study treatment and during the study.
Surgery within 21 days prior to study entry.
Prior treatment with small molecule BET family inhibitor or receiving steroids >the equivalent of 10mg prednisone daily
participants who are currently receiving any other investigational agent or have received an investigational agent within 30 days or 5 half-lives, whichever is longer, prior to study entry
Uncontrolled cancer pain
Prior anti-cancer therapy (chemotherapy, targeted agents, radiotherapy, and immunotherapy) within 14 days except for alkylating agents (e.g., melphalan) within 28 days.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Stanford Cancer Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5820
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Emory Uni - Winship Cancer Center; Hematology/Oncology
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Mount Sinai - PRIME; Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Duke Clin Rsch Institute
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Scientia Clinical Research Limited
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
St Vincent's Hospital Melbourne
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
University College London Hospitals; Clinical Research Facility
City
London
ZIP/Postal Code
W1T 7HA
Country
United Kingdom
Facility Name
Oxford University Hospitals NHS Trust; Churchill Hospital
City
Oxford
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Study of Bromodomain and Extra-Terminal Protein (BET) Inhibitor RO6870810 as Mono- and Combination Therapy in Advanced Multiple Myeloma
We'll reach out to this number within 24 hrs