Trial Outcomes & Findings for Avelumab in Combination With Hypofractionated Radiotherapy in Patients With Relapsed Refractory Multiple Myeloma (NCT NCT03910439)
NCT ID: NCT03910439
Last Updated: 2021-05-12
Results Overview
ORR is defined as participants who experience a partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) per International Myeloma Working Group Criteria (IMWG) 2016 criteria. Complete Response is defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates. Stringent Complete Response is defined as complete response as noted previously plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow biopsy by immune-histochemistry. Partial Response is ≥50% reduction of serum M-protein plus reduction in 24 hour(h) urinary M-protein by ≥90% or to \<200 mg per 24 h. Very Good Partial Response is 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 per 24 h.
TERMINATED
PHASE2
4 participants
up to end of study, an average of 11 months
2021-05-12
Participant Flow
Participant milestones
| Measure |
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy
Avelumab 800 mg IV every two weeks in combination with radiation therapy
Avelumab: Avelumab 800 mg intravenous (IV) over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle
External beam radiotherapy: 5 gray (Gy) per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy
|
|---|---|
|
Overall Study
STARTED
|
4
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Avelumab in Combination With Hypofractionated Radiotherapy in Patients With Relapsed Refractory Multiple Myeloma
Baseline characteristics by cohort
| Measure |
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy
n=4 Participants
Avelumab 800 mg IV every two weeks in combination with radiation therapy
Avelumab: Avelumab 800 mg intravenous (IV) over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle
External beam radiotherapy: 5 gray (Gy) per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
|
Age, Continuous
|
74.44 years
STANDARD_DEVIATION 8.36 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 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
|
0 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
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 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
|
4 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to end of study, an average of 11 monthsORR is defined as participants who experience a partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) per International Myeloma Working Group Criteria (IMWG) 2016 criteria. Complete Response is defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates. Stringent Complete Response is defined as complete response as noted previously plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow biopsy by immune-histochemistry. Partial Response is ≥50% reduction of serum M-protein plus reduction in 24 hour(h) urinary M-protein by ≥90% or to \<200 mg per 24 h. Very Good Partial Response is 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 per 24 h.
Outcome measures
| Measure |
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy
n=4 Participants
Avelumab 800 mg IV every two weeks in combination with radiation therapy
Avelumab: Avelumab 800 mg intravenous (IV) over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle
External beam radiotherapy: 5 gray (Gy) per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy
|
Grade 2
Grade 2 is moderate.
|
Grade 3
Grade 3 is severe or medically significant.
|
|---|---|---|---|
|
Overall Response Rate (ORR)
Complete Response
|
0 Proportion of participants
Interval 0.0 to 0.0
|
—
|
—
|
|
Overall Response Rate (ORR)
Stringent Complete Response
|
0 Proportion of participants
Interval 0.0 to 0.0
|
—
|
—
|
|
Overall Response Rate (ORR)
Partial Response
|
0 Proportion of participants
Interval 0.0 to 0.0
|
—
|
—
|
|
Overall Response Rate (ORR)
Very Good Partial Response
|
0 Proportion of participants
Interval 0.0 to 0.0
|
—
|
—
|
SECONDARY outcome
Timeframe: up to end of study for individual patient, an average of 11 monthsResponse was assessed by the International Myeloma Working Group (IMWG) response criteria, 2016. Complete Response is defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates. Stringent Complete Response is defined as complete response as noted previously plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow biopsy by immune-histochemistry.
Outcome measures
| Measure |
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy
n=4 Participants
Avelumab 800 mg IV every two weeks in combination with radiation therapy
Avelumab: Avelumab 800 mg intravenous (IV) over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle
External beam radiotherapy: 5 gray (Gy) per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy
|
Grade 2
Grade 2 is moderate.
|
Grade 3
Grade 3 is severe or medically significant.
|
|---|---|---|---|
|
Fraction of Participants Who Experience a Complete Response (CR) or Stringent Complete Response (sCR) Using the Study Treatment
|
0 Proportion of participants
Interval 0.0 to 0.0
|
—
|
—
|
SECONDARY outcome
Timeframe: up to up to end of study for individual patient, an average of 11 monthsResponse was assessed by the International Myeloma Working Group Criteria (IMWG) 2016 criteria. Sustained MRDnegCR is defined as negativity in the marrow (next-generation flow (NGF) or next-generation sequencing (NGS), or both) and by imaging confirmed minimum of 1 year apart.
Outcome measures
| Measure |
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy
n=4 Participants
Avelumab 800 mg IV every two weeks in combination with radiation therapy
Avelumab: Avelumab 800 mg intravenous (IV) over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle
External beam radiotherapy: 5 gray (Gy) per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy
|
Grade 2
Grade 2 is moderate.
|
Grade 3
Grade 3 is severe or medically significant.
|
|---|---|---|---|
|
Fraction of Participants Who Experience a Minimal Residual Disease Negative (MRDneg)Complete Response (CR) Using the Study Treatment
|
0 Proportion of participants
Interval 0.0 to 0.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and up to end of study for individual patient, an average of 11 monthsBlood samples and bone marrow samples were taken from participants and processed by flow cytometry.
Outcome measures
| Measure |
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy
n=4 Participants
Avelumab 800 mg IV every two weeks in combination with radiation therapy
Avelumab: Avelumab 800 mg intravenous (IV) over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle
External beam radiotherapy: 5 gray (Gy) per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy
|
Grade 2
Grade 2 is moderate.
|
Grade 3
Grade 3 is severe or medically significant.
|
|---|---|---|---|
|
Percent Change in Aberrant Circulating Plasma Cells in the Peripheral Blood (PB) and Bone Marrow (BM) From Baseline
Peripheral blood at baseline
|
0 Percent change
Interval 0.0 to 0.0
|
—
|
—
|
|
Percent Change in Aberrant Circulating Plasma Cells in the Peripheral Blood (PB) and Bone Marrow (BM) From Baseline
Bone marrow at baseline
|
0 Percent change
Interval 0.0 to 0.0
|
—
|
—
|
|
Percent Change in Aberrant Circulating Plasma Cells in the Peripheral Blood (PB) and Bone Marrow (BM) From Baseline
Peripheral blood at end of study
|
18 Percent change
Interval -1.0 to 1000.0
|
—
|
—
|
|
Percent Change in Aberrant Circulating Plasma Cells in the Peripheral Blood (PB) and Bone Marrow (BM) From Baseline
Bone marrow at end of study
|
55 Percent change
Interval -0.01 to 1250.0
|
—
|
—
|
SECONDARY outcome
Timeframe: end of studyPopulation: This outcome measure was not evaluated due to study closure.
Radiographic reduction in size of non-irradiated extramedullary lesions.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: End of studyPopulation: This outcome measure was not evaluated due to study closure.
FDG avidity of extramedullary lesions.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: End of study, an average of 11 monthsPFS was defined as those who progress or die without progression as failures, and censoring those who do not. Progressive disease was assessed by the 2016 International Myeloma Working Group (IMWG) response criteria and is an increase of 25% from lowest confirmed response value in one or more of the following criteria: Serum M-protein (absolute increase must be ≥0·5 g/dL); Serum M-protein increase ≥1 g/dL, if the lowest M component was ≥5 g/dL; Urine M-protein (absolute increase must be ≥200 mg/24 h); In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be \>10 mg/dL).
Outcome measures
| Measure |
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy
n=4 Participants
Avelumab 800 mg IV every two weeks in combination with radiation therapy
Avelumab: Avelumab 800 mg intravenous (IV) over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle
External beam radiotherapy: 5 gray (Gy) per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy
|
Grade 2
Grade 2 is moderate.
|
Grade 3
Grade 3 is severe or medically significant.
|
|---|---|---|---|
|
Progression-free Survival (PFS)
|
5.3 Months
Interval 2.5 to 7.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Enrollment through end of study, an average of 11 monthsParticipants who are alive following enrollment and study treatment.
Outcome measures
| Measure |
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy
n=4 Participants
Avelumab 800 mg IV every two weeks in combination with radiation therapy
Avelumab: Avelumab 800 mg intravenous (IV) over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle
External beam radiotherapy: 5 gray (Gy) per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy
|
Grade 2
Grade 2 is moderate.
|
Grade 3
Grade 3 is severe or medically significant.
|
|---|---|---|---|
|
Percentage of Participants With Overall Survival (OS)
|
100 percentage of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Date treatment consent signed to date off study, approximately 14 months and 4 days.Grade ≥1 non-serious adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. Grade 1 is mild, Grade 2 is moderate, and Grade 3 is severe or medically significant.
Outcome measures
| Measure |
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy
n=4 Participants
Avelumab 800 mg IV every two weeks in combination with radiation therapy
Avelumab: Avelumab 800 mg intravenous (IV) over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle
External beam radiotherapy: 5 gray (Gy) per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy
|
Grade 2
n=4 Participants
Grade 2 is moderate.
|
Grade 3
n=4 Participants
Grade 3 is severe or medically significant.
|
|---|---|---|---|
|
Number of Participants With Grade ≥1 Non-serious Adverse Events
Skin infection
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Grade ≥1 Non-serious Adverse Events
Alanine aminotransferase increased
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade ≥1 Non-serious Adverse Events
Alkaline aminotransferase increased
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Grade ≥1 Non-serious Adverse Events
Arthralgia
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Grade ≥1 Non-serious Adverse Events
Aspartate aminotransferase increased
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade ≥1 Non-serious Adverse Events
Chest pain - cardiac
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade ≥1 Non-serious Adverse Events
Eye disorders - Other, posterior vitreous detachment
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Grade ≥1 Non-serious Adverse Events
Nausea
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Grade ≥1 Non-serious Adverse Events
Pain
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade ≥1 Non-serious Adverse Events
Rash maculo-papular
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Grade ≥1 Non-serious Adverse Events
Syncope
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Grade ≥1 Non-serious Adverse Events
Vomiting
|
0 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 4 weeksResponse was assessed by the International Myeloma Working Group (IMWG) response criteria, 2016. Minimal Response is ≥25% but ≤49% reduction of serum M-protein and reduction in 24-h urine M-protein by 50-89%; in addition, if present at baseline, a ≥50% reduction in the size (SPD) of soft tissue plasmacytomas is also required. Stable Disease is not meeting criteria for complete response, very good partial response, partial response, minimal response, or progressive disease. And Progressive Disease is appearance of a new lesion(s), ≥50% increase from nadir in sum of the products of diameters (SPD) of \>1 lesion, or ≥50% increase in the longest diameter of a previous lesion \>1 cm in short axis; ≥50% increase in circulating plasma cells (minimum of 200 cells per microliter (μL) if this is the only measure of disease.
Outcome measures
| Measure |
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy
n=4 Participants
Avelumab 800 mg IV every two weeks in combination with radiation therapy
Avelumab: Avelumab 800 mg intravenous (IV) over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle
External beam radiotherapy: 5 gray (Gy) per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy
|
Grade 2
Grade 2 is moderate.
|
Grade 3
Grade 3 is severe or medically significant.
|
|---|---|---|---|
|
Number of Participants Overall Best Response
Minimal Response
|
1 Participants
|
—
|
—
|
|
Number of Participants Overall Best Response
Stable Disease
|
2 Participants
|
—
|
—
|
|
Number of Participants Overall Best Response
Progressive Disease
|
1 Participants
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Date treatment consent signed to date off study, approximately 14 months and 4 days.Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence.
Outcome measures
| Measure |
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy
n=4 Participants
Avelumab 800 mg IV every two weeks in combination with radiation therapy
Avelumab: Avelumab 800 mg intravenous (IV) over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle
External beam radiotherapy: 5 gray (Gy) per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy
|
Grade 2
Grade 2 is moderate.
|
Grade 3
Grade 3 is severe or medically significant.
|
|---|---|---|---|
|
Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
|
4 Participants
|
—
|
—
|
Adverse Events
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy
n=4 participants at risk
Avelumab 800 mg IV every two weeks in combination with radiation therapy
Avelumab: Avelumab 800 mg intravenous (IV) over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle
External beam radiotherapy: 5 gray (Gy) per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy
|
|---|---|
|
Investigations
Alanine aminotransferase increased
|
25.0%
1/4 • Number of events 3 • Date treatment consent signed to date off study, approximately 14 months and 4 days.
|
|
Investigations
Alkaline phosphatase increased
|
25.0%
1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 4 days.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
25.0%
1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 4 days.
|
|
Investigations
Aspartate aminotransferase increased
|
25.0%
1/4 • Number of events 2 • Date treatment consent signed to date off study, approximately 14 months and 4 days.
|
|
Musculoskeletal and connective tissue disorders
Chest pain - cardiac
|
25.0%
1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 4 days.
|
|
Eye disorders
Eye disorders - Other, posterior vitreous detachment
|
25.0%
1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 4 days.
|
|
Gastrointestinal disorders
Nausea
|
25.0%
1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 4 days.
|
|
General disorders
Pain
|
25.0%
1/4 • Number of events 2 • Date treatment consent signed to date off study, approximately 14 months and 4 days.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
25.0%
1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 4 days.
|
|
Infections and infestations
Skin infection
|
25.0%
1/4 • Number of events 2 • Date treatment consent signed to date off study, approximately 14 months and 4 days.
|
|
Nervous system disorders
Syncope
|
25.0%
1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 4 days.
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 4 days.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place