Study of Ciforadenant in Combination With Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ciforadenant
daratumumab
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Relapsed or refractory myeloma.
- Must have been exposed to at least 2 cycles of an IMiD containing regimen and PI containing regimen and must be refractory to at least one of the two.
- Must have completed and tolerated 2 cycles of daratumumab or other anti-CD38 targeting antibodies.
- Active myeloma requiring systemic treatment.
- Measurable disease per protocol.
- ECOG performance status of 0 - 2.
- Life expectancy of at least 3 months.
Exclusion Criteria:
- POEMS syndrome; non-secretory myeloma (no measurable protein on sFLC assay); amyloidosis.
- History of select prior malignancies.
- Previous intolerance to daratumumab or any study drug.
- Received an allogeneic stem cell transplant within 12 months, or an autologous stem cell transplant within 6 months, or have ongoing toxicity related to transplant.
- Have an active infection or serious comorbid medical condition.
- Any live attenuated vaccination against infectious diseases (e.g., influenza, varicella) within 4 weeks of initiation of study treatment; uncontrolled human immunodeficiency virus, or positive tests for hepatitis B or hepatitis C.
- Female participants pregnant or breast-feeding.
- Screening chemistry and blood counts within protocol limits
- Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment.
Sites / Locations
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ciforadenant in combination with daratumumab
Arm Description
Ciforadenant 100 mg orally twice daily in combination with daratumumab IV 16 mg/kg.
Outcomes
Primary Outcome Measures
Safety and tolerability of ciforadenant in combination with daratumumab relapsed / refractory multiple myeloma.
Incidence of treatment-emergent adverse events, as assessed by NCI CTCAE v.5
Safety and tolerability of ciforadenant in combination with daratumumab relapsed / refractory multiple myeloma.
Incidence of dose-limiting toxicities (DLTs) of CPI-444 in combination with daratumumab
Secondary Outcome Measures
Overall response rate.
According to international myeloma working group guidelines (including stringent complete response [sCR], complete response [CR], very good partial response [VGPR], partial response [PR]).
Duration of response.
Time from the first assessment showing objective response to the date of documented disease progression.
Disease control rate.
Proportion of participants achieving disease control for ≥ 3 months.
Time to next therapy.
Time from end of treatment to starting next anti-myeloma therapy.
Progression free survival.
Proportion of participants remaining progression free or surviving at a given time.
Minimal Residual Disease.
Rate of molecular minimal residual disease (MRD) negativity.
Full Information
NCT ID
NCT04280328
First Posted
February 19, 2020
Last Updated
March 9, 2022
Sponsor
Corvus Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04280328
Brief Title
Study of Ciforadenant in Combination With Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma
Official Title
An Open-Label Study of Ciforadenant in Combination With Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
February 20, 2020 (Actual)
Primary Completion Date
September 21, 2021 (Actual)
Study Completion Date
March 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Corvus Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This is a Phase 1b open-label study of ciforadenant, an oral, small molecule inhibitor targeting adenosine-2A receptors (A2AR), on safety/tolerability and efficacy in combination with daratumumab, a monoclonal antibody targeting CD38, in relapsed or refractory multiple myeloma.
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
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ciforadenant in combination with daratumumab
Arm Type
Experimental
Arm Description
Ciforadenant 100 mg orally twice daily in combination with daratumumab IV 16 mg/kg.
Intervention Type
Drug
Intervention Name(s)
Ciforadenant
Other Intervention Name(s)
CPI-444
Intervention Description
100 mg orally twice daily for 28-day cycles
Intervention Type
Drug
Intervention Name(s)
daratumumab
Intervention Description
16 mg/kg administered intravenously as follows based on 28-day cycles:
Cycles 1 - 2: Days 1, 8, 15, and 22
Cycles 3 - 6: Days 1 and 15
Cycles 7 - 24: Day 1
Primary Outcome Measure Information:
Title
Safety and tolerability of ciforadenant in combination with daratumumab relapsed / refractory multiple myeloma.
Description
Incidence of treatment-emergent adverse events, as assessed by NCI CTCAE v.5
Time Frame
From start of treatment to end of treatment, up to 24 months
Title
Safety and tolerability of ciforadenant in combination with daratumumab relapsed / refractory multiple myeloma.
Description
Incidence of dose-limiting toxicities (DLTs) of CPI-444 in combination with daratumumab
Time Frame
28 days following first administration of ciforadnenat in combination with daratumumab
Secondary Outcome Measure Information:
Title
Overall response rate.
Description
According to international myeloma working group guidelines (including stringent complete response [sCR], complete response [CR], very good partial response [VGPR], partial response [PR]).
Time Frame
From start of treatment to end of treatment, up to 24 months
Title
Duration of response.
Description
Time from the first assessment showing objective response to the date of documented disease progression.
Time Frame
From start of treatment to end of treatment, up to 24 months
Title
Disease control rate.
Description
Proportion of participants achieving disease control for ≥ 3 months.
Time Frame
From start of treatment to end of treatment, up to 24 months
Title
Time to next therapy.
Description
Time from end of treatment to starting next anti-myeloma therapy.
Time Frame
Up to 2 years after end of treatment.
Title
Progression free survival.
Description
Proportion of participants remaining progression free or surviving at a given time.
Time Frame
Up to 2 years after end of treatment.
Title
Minimal Residual Disease.
Description
Rate of molecular minimal residual disease (MRD) negativity.
Time Frame
From start of treatment to end of treatment, up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Relapsed or refractory myeloma.
Must have been exposed to at least 2 cycles of an IMiD containing regimen and PI containing regimen and must be refractory to at least one of the two.
Must have completed and tolerated 2 cycles of daratumumab or other anti-CD38 targeting antibodies.
Active myeloma requiring systemic treatment.
Measurable disease per protocol.
ECOG performance status of 0 - 2.
Life expectancy of at least 3 months.
Exclusion Criteria:
POEMS syndrome; non-secretory myeloma (no measurable protein on sFLC assay); amyloidosis.
History of select prior malignancies.
Previous intolerance to daratumumab or any study drug.
Received an allogeneic stem cell transplant within 12 months, or an autologous stem cell transplant within 6 months, or have ongoing toxicity related to transplant.
Have an active infection or serious comorbid medical condition.
Any live attenuated vaccination against infectious diseases (e.g., influenza, varicella) within 4 weeks of initiation of study treatment; uncontrolled human immunodeficiency virus, or positive tests for hepatitis B or hepatitis C.
Female participants pregnant or breast-feeding.
Screening chemistry and blood counts within protocol limits
Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deborah Strahs
Organizational Affiliation
Corvus Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Ciforadenant in Combination With Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma
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