Trial Outcomes & Findings for Daratumumab, Azacitidine, and Dexamethasone for Treatment of Patients With Recurrent or Refractory Multiple Myeloma Previously Treated With Daratumumab (NCT NCT04407442)
NCT ID: NCT04407442
Last Updated: 2024-04-30
Results Overview
ORR is defined as the proportion of participants with either a stringent complete response (sCR) + complete response (CR) + very good partial response + partial response (PR) as best response using International Myeloma Working Group (IMWG) Uniform Response Criteria for all subjects who have measurable disease and received at least 2 cycles of study treatment, and have at least 2 efficacy evaluation assessments.
TERMINATED
PHASE2
5 participants
Up to 18 months
2024-04-30
Participant Flow
Participant milestones
| Measure |
Treatment (Azacitidine, Dexamethasone, Daratumumab)
PRE-INDUCTION (CYCLE 0): Patients receive azacitidine IV on days -7 to -3 in absence of disease progression or unacceptable toxicity.
INDUCTION (CYCLES 1-2): Patients receive azacitidine IV on days 22-26, dexamethasone IV or orally (PO), and daratumumab subcutaneously (SC) over 3-5 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity
CONSOLIDATION (CYCLES 3-6): Patients receive azacitidine IV on days 22-26 of cycle 3 and on days 1-5 of cycles 5-6, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity
MAINTENANCE (CYCLES 7+): Patients receive azacitidine IV on days 1-5, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity
|
|---|---|
|
Overall Study
STARTED
|
5
|
|
Overall Study
COMPLETED
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Daratumumab, Azacitidine, and Dexamethasone for Treatment of Patients With Recurrent or Refractory Multiple Myeloma Previously Treated With Daratumumab
Baseline characteristics by cohort
| Measure |
Treatment (Azacitidine, Dexamethasone, Daratumumab)
n=5 Participants
PRE-INDUCTION (CYCLE 0): Patients receive azacitidine IV on days -7 to -3 in absence of disease progression or unacceptable toxicity.
INDUCTION (CYCLES 1-2): Patients receive azacitidine IV on days 22-26, dexamethasone IV or orally (PO), and daratumumab subcutaneously (SC) over 3-5 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity
CONSOLIDATION (CYCLES 3-6): Patients receive azacitidine IV on days 22-26 of cycle 3 and on days 1-5 of cycles 5-6, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity
MAINTENANCE (CYCLES 7+): Patients receive azacitidine IV on days 1-5, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity
|
|---|---|
|
Age, Customized
60-69 years old
|
3 Participants
n=5 Participants
|
|
Age, Customized
70-79 years old
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 18 monthsPopulation: One participant has insufficient imaging data required for efficacy evaluation and was excluded from this analysis
ORR is defined as the proportion of participants with either a stringent complete response (sCR) + complete response (CR) + very good partial response + partial response (PR) as best response using International Myeloma Working Group (IMWG) Uniform Response Criteria for all subjects who have measurable disease and received at least 2 cycles of study treatment, and have at least 2 efficacy evaluation assessments.
Outcome measures
| Measure |
Treatment (Azacitidine, Dexamethasone, Daratumumab)
n=4 Participants
PRE-INDUCTION (CYCLE 0): Patients receive azacitidine IV on days -7 to -3 in absence of disease progression or unacceptable toxicity.
INDUCTION (CYCLES 1-2): Patients receive azacitidine IV on days 22-26, dexamethasone IV or orally (PO), and daratumumab subcutaneously (SC) over 3-5 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity
CONSOLIDATION (CYCLES 3-6): Patients receive azacitidine IV on days 22-26 of cycle 3 and on days 1-5 of cycles 5-6, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity
MAINTENANCE (CYCLES 7+): Patients receive azacitidine IV on days 1-5, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity
|
|---|---|
|
Overall Response Rate (ORR)
|
0.75 proportion of participants
|
SECONDARY outcome
Timeframe: Up to 18 monthsAll safety analyses for AEs will be based on all subjects who receive at least 1 cycle of study treatment. AEs will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 from the initiation of study treatment until discontinuation of treatment. For each treatment-related adverse event, the number of subjects who experience at least 1 occurrence of the given event which was attributed to the study regimen as probable, possible or definite will be summarized.
Outcome measures
| Measure |
Treatment (Azacitidine, Dexamethasone, Daratumumab)
n=5 Participants
PRE-INDUCTION (CYCLE 0): Patients receive azacitidine IV on days -7 to -3 in absence of disease progression or unacceptable toxicity.
INDUCTION (CYCLES 1-2): Patients receive azacitidine IV on days 22-26, dexamethasone IV or orally (PO), and daratumumab subcutaneously (SC) over 3-5 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity
CONSOLIDATION (CYCLES 3-6): Patients receive azacitidine IV on days 22-26 of cycle 3 and on days 1-5 of cycles 5-6, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity
MAINTENANCE (CYCLES 7+): Patients receive azacitidine IV on days 1-5, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity
|
|---|---|
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Number of Participants With Reported Treatment-related Adverse Events (AE)
Injection site reaction
|
4 participants
|
|
Number of Participants With Reported Treatment-related Adverse Events (AE)
White blood cell decreased
|
1 participants
|
|
Number of Participants With Reported Treatment-related Adverse Events (AE)
Hyperglycemia
|
1 participants
|
|
Number of Participants With Reported Treatment-related Adverse Events (AE)
Insomnia
|
1 participants
|
|
Number of Participants With Reported Treatment-related Adverse Events (AE)
Diarrhea
|
1 participants
|
|
Number of Participants With Reported Treatment-related Adverse Events (AE)
Lymphocyte count decreased
|
1 participants
|
|
Number of Participants With Reported Treatment-related Adverse Events (AE)
Nausea
|
2 participants
|
|
Number of Participants With Reported Treatment-related Adverse Events (AE)
Platelet count decreased
|
1 participants
|
|
Number of Participants With Reported Treatment-related Adverse Events (AE)
Pruritus
|
1 participants
|
|
Number of Participants With Reported Treatment-related Adverse Events (AE)
Sore Throat
|
1 participants
|
|
Number of Participants With Reported Treatment-related Adverse Events (AE)
Upper respiratory infection
|
1 participants
|
|
Number of Participants With Reported Treatment-related Adverse Events (AE)
Eye Pain
|
1 participants
|
|
Number of Participants With Reported Treatment-related Adverse Events (AE)
Neutrophil count decreased
|
3 participants
|
|
Number of Participants With Reported Treatment-related Adverse Events (AE)
Chills
|
1 participants
|
SECONDARY outcome
Timeframe: Up to 18 monthsPopulation: One participant has insufficient imaging data required for efficacy evaluation and was excluded from this analysis
DOR is defined as the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG criteria or death due to progressive disease whichever occurred first all subjects who have measurable disease and received at least 2 cycles of study treatment, and have at least 2 efficacy evaluation assessments. DOR will be summarized using the Kaplan-Meier estimator. Median even-free survival will be reported and the corresponding 95% confidence interval will be calculated using Brookmeyer and Crowley method.
Outcome measures
| Measure |
Treatment (Azacitidine, Dexamethasone, Daratumumab)
n=4 Participants
PRE-INDUCTION (CYCLE 0): Patients receive azacitidine IV on days -7 to -3 in absence of disease progression or unacceptable toxicity.
INDUCTION (CYCLES 1-2): Patients receive azacitidine IV on days 22-26, dexamethasone IV or orally (PO), and daratumumab subcutaneously (SC) over 3-5 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity
CONSOLIDATION (CYCLES 3-6): Patients receive azacitidine IV on days 22-26 of cycle 3 and on days 1-5 of cycles 5-6, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity
MAINTENANCE (CYCLES 7+): Patients receive azacitidine IV on days 1-5, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity
|
|---|---|
|
Duration of Response (DOR)
|
9.1 months
Interval 1.4 to
There were insufficient number of events so an upper limit could not be calculated
|
SECONDARY outcome
Timeframe: Up to 18 monthsOS is defined as the date of first dose of study treatment to the date of death due to any cause or censored based on the date of last encounter if patient is alive or lost to follow-up. OS will be summarized using the Kaplan-Meier estimator. Median even-free survival will be reported and the corresponding 95% confidence interval will be calculated using Brookmeyer and Crowley method.
Outcome measures
| Measure |
Treatment (Azacitidine, Dexamethasone, Daratumumab)
n=5 Participants
PRE-INDUCTION (CYCLE 0): Patients receive azacitidine IV on days -7 to -3 in absence of disease progression or unacceptable toxicity.
INDUCTION (CYCLES 1-2): Patients receive azacitidine IV on days 22-26, dexamethasone IV or orally (PO), and daratumumab subcutaneously (SC) over 3-5 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity
CONSOLIDATION (CYCLES 3-6): Patients receive azacitidine IV on days 22-26 of cycle 3 and on days 1-5 of cycles 5-6, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity
MAINTENANCE (CYCLES 7+): Patients receive azacitidine IV on days 1-5, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity
|
|---|---|
|
Overall Survival (OS)
|
NA months
Interval 10.1 to
There were insufficient number of events (N=1) to determine median OS and upper limit of confidence interval could not be calculated
|
SECONDARY outcome
Timeframe: Up to 18 monthsPopulation: One participant has insufficient imaging data required for efficacy evaluation and was excluded from this analysis
PFS is defined as the date of first dose of study treatment to the date of first documented evidence of progressive disease or death, whichever occurs first. PFS will be summarized using the Kaplan-Meier estimator. Median even-free survival will be reported and the corresponding 95% confidence interval will be calculated using Brookmeyer and Crowley method.
Outcome measures
| Measure |
Treatment (Azacitidine, Dexamethasone, Daratumumab)
n=4 Participants
PRE-INDUCTION (CYCLE 0): Patients receive azacitidine IV on days -7 to -3 in absence of disease progression or unacceptable toxicity.
INDUCTION (CYCLES 1-2): Patients receive azacitidine IV on days 22-26, dexamethasone IV or orally (PO), and daratumumab subcutaneously (SC) over 3-5 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity
CONSOLIDATION (CYCLES 3-6): Patients receive azacitidine IV on days 22-26 of cycle 3 and on days 1-5 of cycles 5-6, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity
MAINTENANCE (CYCLES 7+): Patients receive azacitidine IV on days 1-5, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity
|
|---|---|
|
Progression-free Survival (PFS)
|
10.3 months
Interval 2.66 to
There were insufficient number of events so an upper limit could not be calculated
|
SECONDARY outcome
Timeframe: Starting 6 days before treatment up until the end of cycle 1 (each cycle is 28 days); up to 34 days totalPopulation: Data not collected for this endpoint
Change in CD38 surface expression will be summarized using descriptive statistics and tested using the one-sample t-test. Two-sided p-value less than 0.05 will be considered statistically significant.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At the end of cycle 1 (each cycle is 28 days)Population: Data not collected for this endpoint
Will be assessed by flow cytometry and based on a one-sample t-test at a two-sided type I error rate of 0.05.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 18 monthsPopulation: Data not collected for this endpoint
Will be correlated to overall response using logistic regression, linear regression methods, and Spearman's correlation coefficient, as appropriate.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 18 monthsPopulation: Data not collected for this endpoint
Correlation will be calculated using logistic regression, linear regression methods, and Spearman's correlation coefficient, as appropriate.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 18 monthsPopulation: Data not collected for this endpoint
Will be correlated to duration of response using logistic regression, linear regression methods, and Spearman's correlation coefficient, as appropriate.
Outcome measures
Outcome data not reported
Adverse Events
Treatment (Azacitidine, Dexamethasone, Daratumumab)
Serious adverse events
| Measure |
Treatment (Azacitidine, Dexamethasone, Daratumumab)
n=5 participants at risk
PRE-INDUCTION (CYCLE 0): Patients receive azacitidine IV on days -7 to -3 in absence of disease progression or unacceptable toxicity.
INDUCTION (CYCLES 1-2): Patients receive azacitidine IV on days 22-26, dexamethasone IV or orally (PO), and daratumumab subcutaneously (SC) over 3-5 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity
CONSOLIDATION (CYCLES 3-6): Patients receive azacitidine IV on days 22-26 of cycle 3 and on days 1-5 of cycles 5-6, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity
MAINTENANCE (CYCLES 7+): Patients receive azacitidine IV on days 1-5, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity
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|---|---|
|
Infections and infestations
Upper respiratory infection
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
Other adverse events
| Measure |
Treatment (Azacitidine, Dexamethasone, Daratumumab)
n=5 participants at risk
PRE-INDUCTION (CYCLE 0): Patients receive azacitidine IV on days -7 to -3 in absence of disease progression or unacceptable toxicity.
INDUCTION (CYCLES 1-2): Patients receive azacitidine IV on days 22-26, dexamethasone IV or orally (PO), and daratumumab subcutaneously (SC) over 3-5 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity
CONSOLIDATION (CYCLES 3-6): Patients receive azacitidine IV on days 22-26 of cycle 3 and on days 1-5 of cycles 5-6, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity
MAINTENANCE (CYCLES 7+): Patients receive azacitidine IV on days 1-5, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity
|
|---|---|
|
General disorders
Fever
|
80.0%
4/5 • Number of events 5 • Up to 18 months
|
|
General disorders
Injection site reaction
|
80.0%
4/5 • Number of events 13 • Up to 18 months
|
|
General disorders
Fatigue
|
60.0%
3/5 • Number of events 6 • Up to 18 months
|
|
General disorders
Chills
|
20.0%
1/5 • Number of events 2 • Up to 18 months
|
|
General disorders
Malaise
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
General disorders
Pain
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Investigations
Neutrophil count decreased
|
60.0%
3/5 • Number of events 13 • Up to 18 months
|
|
Investigations
Creatinine increased
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Investigations
Lymphocyte count decreased
|
20.0%
1/5 • Number of events 2 • Up to 18 months
|
|
Investigations
Platelet count decreased
|
20.0%
1/5 • Number of events 4 • Up to 18 months
|
|
Investigations
White blood cell decreased
|
20.0%
1/5 • Number of events 2 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
40.0%
2/5 • Number of events 2 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
20.0%
1/5 • Number of events 3 • Up to 18 months
|
|
Gastrointestinal disorders
Nausea
|
60.0%
3/5 • Number of events 4 • Up to 18 months
|
|
Gastrointestinal disorders
Constipation
|
40.0%
2/5 • Number of events 3 • Up to 18 months
|
|
Gastrointestinal disorders
Diarrhea
|
20.0%
1/5 • Number of events 3 • Up to 18 months
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
20.0%
1/5 • Number of events 2 • Up to 18 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Infections and infestations
Lung infection
|
20.0%
1/5 • Number of events 2 • Up to 18 months
|
|
Infections and infestations
Penile infection
|
20.0%
1/5 • Number of events 2 • Up to 18 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Nervous system disorders
Dizziness
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Blood and lymphatic system disorders
Anemia
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Ear and labyrinth disorders
Vertigo
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Eye disorders
Eye pain
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Psychiatric disorders
Insomnia
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Renal and urinary disorders
Dysuria
|
20.0%
1/5 • Number of events 2 • Up to 18 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
|
Vascular disorders
Hypotension
|
20.0%
1/5 • Number of events 1 • Up to 18 months
|
Additional Information
Dr. Alfred Chung
University of California, San Francisco
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place