Trial Outcomes & Findings for Radiotherapy With Immunotherapy for Systemic Effect in Myeloma (RISE-M) (NCT NCT03634800)

Last Updated: 2021-08-05

Results Overview

The primary aim is to estimate the overall response at 12 weeks using IMWG criteria. Per IMWG response criteria, Complete Response (CR) is defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow; Very Good Partial Response (VGPR) is defined as 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/24 h; Partial Response (PR) is defined as \> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \< 200 mg/24 h, No change/Stable disease is defined as not meeting criteria for CR, VGPR, PR, or progressive disease; Progressive disease (PD) is defined as an increase of \> 25% from lowest response value; Relapse is define as development of new soft tissue plasmacytomas or Definite increase in the size of existing plasmacytomas or bone lesions.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

12 weeks

Results posted on

2021-08-05

Participant Flow

Patients were screened and enrolled at 1 site in the US: Weill Cornell Medicine (NY, NY).

Participant milestones

Participant milestones
Measure	Nivolumab/Radiotherapy All eligible patients will receive immunotherapy (Nivolumab) plus radiotherapy (6 Gy x 5 fractions) to a targetable lesion. * Nivolumab 240 mg IV starts with the first radiotherapy fraction 240 mg IV every 2 weeks from first radiotherapy fraction until disease prograssion or dose limiting toxicity is reached * Radiotherapy Dose of 6 Gy x 5 days will be given (patients will receive 1 fraction over 5 days for a total of 5 fractions) during the first week of starting Nivolumab Nivolumab 240mg: Patients with multiple myeloma will receive Nivolumab intravenously at 240 mg every two weeks. Infusions will be given over 60 minutes (not bolus or IV push). Patients will continue to receive infusions every two weeks until disease progression or dose limiting toxicity is reached. Radiation therapy: Patients will receive radiation for 5 consecutive days. A dose of 6 Gy x 5 days will be administered. Patients may receive radiotherapy to an additional site at 12 weeks if they have stable disease.
Overall Study STARTED	6
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Nivolumab/Radiotherapy All eligible patients will receive immunotherapy (Nivolumab) plus radiotherapy (6 Gy x 5 fractions) to a targetable lesion. * Nivolumab 240 mg IV starts with the first radiotherapy fraction 240 mg IV every 2 weeks from first radiotherapy fraction until disease prograssion or dose limiting toxicity is reached * Radiotherapy Dose of 6 Gy x 5 days will be given (patients will receive 1 fraction over 5 days for a total of 5 fractions) during the first week of starting Nivolumab Nivolumab 240mg: Patients with multiple myeloma will receive Nivolumab intravenously at 240 mg every two weeks. Infusions will be given over 60 minutes (not bolus or IV push). Patients will continue to receive infusions every two weeks until disease progression or dose limiting toxicity is reached. Radiation therapy: Patients will receive radiation for 5 consecutive days. A dose of 6 Gy x 5 days will be administered. Patients may receive radiotherapy to an additional site at 12 weeks if they have stable disease.
Overall Study Adverse Event	1
Overall Study Disease Progression	4
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Radiotherapy With Immunotherapy for Systemic Effect in Myeloma (RISE-M)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nivolumab/Radiotherapy n=5 Participants All eligible patients will receive immunotherapy (Nivolumab) plus radiotherapy (6 Gy x 5 fractions) to a targetable lesion. * Nivolumab 240 mg IV starts with the first radiotherapy fraction 240 mg IV every 2 weeks from first radiotherapy fraction until disease prograssion or dose limiting toxicity is reached * Radiotherapy Dose of 6 Gy x 5 days will be given (patients will receive 1 fraction over 5 days for a total of 5 fractions) during the first week of starting Nivolumab Nivolumab 240mg: Patients with multiple myeloma will receive Nivolumab intravenously at 240 mg every two weeks. Infusions will be given over 60 minutes (not bolus or IV push). Patients will continue to receive infusions every two weeks until disease progression or dose limiting toxicity is reached. Radiation therapy: Patients will receive radiation for 5 consecutive days. A dose of 6 Gy x 5 days will be administered. Patients may receive radiotherapy to an additional site at 12 weeks if they have stable disease.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=99 Participants
Age, Categorical >=65 years	3 Participants n=99 Participants
Age, Continuous	59.4 years n=99 Participants
Sex: Female, Male Female	3 Participants n=99 Participants
Sex: Female, Male Male	2 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	3 Participants n=99 Participants
Race (NIH/OMB) More than one race	2 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Out of the 5 patients that started treatment, only 3 patient made it to 12 weeks of treatment.

Outcome measures

Outcome measures
Measure	Nivolumab/Radiotherapy n=3 Participants All eligible patients will receive immunotherapy (Nivolumab) plus radiotherapy (6 Gy x 5 fractions) to a targetable lesion. * Nivolumab 240 mg IV starts with the first radiotherapy fraction 240 mg IV every 2 weeks from first radiotherapy fraction until disease prograssion or dose limiting toxicity is reached * Radiotherapy Dose of 6 Gy x 5 days will be given (patients will receive 1 fraction over 5 days for a total of 5 fractions) during the first week of starting Nivolumab Nivolumab 240mg: Patients with multiple myeloma will receive Nivolumab intravenously at 240 mg every two weeks. Infusions will be given over 60 minutes (not bolus or IV push). Patients will continue to receive infusions every two weeks until disease progression or dose limiting toxicity is reached. Radiation therapy: Patients will receive radiation for 5 consecutive days. A dose of 6 Gy x 5 days will be administered. Patients may receive radiotherapy to an additional site at 12 weeks if they have stable disease.
To Determine Overall Response at 12 Weeks Using International Myeloma Working Group (IMWG) Criteria in Patients Will be Measured CR (complete response)	0 Participants
To Determine Overall Response at 12 Weeks Using International Myeloma Working Group (IMWG) Criteria in Patients Will be Measured VGPR (Very Good Partial Response)	0 Participants
To Determine Overall Response at 12 Weeks Using International Myeloma Working Group (IMWG) Criteria in Patients Will be Measured PR (Partial Response)	0 Participants
To Determine Overall Response at 12 Weeks Using International Myeloma Working Group (IMWG) Criteria in Patients Will be Measured No change/Stable disease	1 Participants
To Determine Overall Response at 12 Weeks Using International Myeloma Working Group (IMWG) Criteria in Patients Will be Measured PD (Progressive disease)	2 Participants
To Determine Overall Response at 12 Weeks Using International Myeloma Working Group (IMWG) Criteria in Patients Will be Measured Relapse	0 Participants

SECONDARY outcome

Timeframe: through study completion

Population: 4 patient progressed while on study.

Median progression free survival for patients treated with immunotherapy and radiotherapy will be assessed. Progression free survival (PFS) will be defined as the time from first treatment day until objective or symptomatic progression. PFS will be defined as the time from first treatment day until objective or symptomatic progression and PFS will be assessed by Kaplan-Meier survival analysis and 95% confidence interval.

Outcome measures

Outcome measures
Measure	Nivolumab/Radiotherapy n=4 Participants All eligible patients will receive immunotherapy (Nivolumab) plus radiotherapy (6 Gy x 5 fractions) to a targetable lesion. * Nivolumab 240 mg IV starts with the first radiotherapy fraction 240 mg IV every 2 weeks from first radiotherapy fraction until disease prograssion or dose limiting toxicity is reached * Radiotherapy Dose of 6 Gy x 5 days will be given (patients will receive 1 fraction over 5 days for a total of 5 fractions) during the first week of starting Nivolumab Nivolumab 240mg: Patients with multiple myeloma will receive Nivolumab intravenously at 240 mg every two weeks. Infusions will be given over 60 minutes (not bolus or IV push). Patients will continue to receive infusions every two weeks until disease progression or dose limiting toxicity is reached. Radiation therapy: Patients will receive radiation for 5 consecutive days. A dose of 6 Gy x 5 days will be administered. Patients may receive radiotherapy to an additional site at 12 weeks if they have stable disease.
To Determine the Median Progression Free Survival (PFS) Will be Assessed in Patients Treated With Immunotherapy and Radiotherapy.	33.75 days Interval 21.0 to 56.0

SECONDARY outcome

Timeframe: through study completion

Population: All patients withdrew consent after progressing, so no follow up survival data was collected (with the exception of 1 patient who only allowed for survival follow up after being taken off study for progression).

Median overall survival for patients treated with immunotherapy and radiotherapy will be assessed. overall survival will be defined as the time from first treatment day until death. Overall survival will be assessed by Kaplan-Meier survival analysis and 95% confidence interval.

Outcome measures

Outcome measures
Measure	Nivolumab/Radiotherapy n=1 Participants All eligible patients will receive immunotherapy (Nivolumab) plus radiotherapy (6 Gy x 5 fractions) to a targetable lesion. * Nivolumab 240 mg IV starts with the first radiotherapy fraction 240 mg IV every 2 weeks from first radiotherapy fraction until disease prograssion or dose limiting toxicity is reached * Radiotherapy Dose of 6 Gy x 5 days will be given (patients will receive 1 fraction over 5 days for a total of 5 fractions) during the first week of starting Nivolumab Nivolumab 240mg: Patients with multiple myeloma will receive Nivolumab intravenously at 240 mg every two weeks. Infusions will be given over 60 minutes (not bolus or IV push). Patients will continue to receive infusions every two weeks until disease progression or dose limiting toxicity is reached. Radiation therapy: Patients will receive radiation for 5 consecutive days. A dose of 6 Gy x 5 days will be administered. Patients may receive radiotherapy to an additional site at 12 weeks if they have stable disease.
To Determine the Median Overall Survival for Patients Treated With Immunotherapy and Radiotherapy Will be Assessed.	17.96 months Interval 17.96 to 17.96

Adverse Events

Nivolumab/Radiotherapy

Serious events: 2 serious events

Other events: 5 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Nivolumab/Radiotherapy n=5 participants at risk All eligible patients will receive immunotherapy (Nivolumab) plus radiotherapy (6 Gy x 5 fractions) to a targetable lesion. * Nivolumab 240 mg IV starts with the first radiotherapy fraction 240 mg IV every 2 weeks from first radiotherapy fraction until disease prograssion or dose limiting toxicity is reached * Radiotherapy Dose of 6 Gy x 5 days will be given (patients will receive 1 fraction over 5 days for a total of 5 fractions) during the first week of starting Nivolumab Nivolumab 240mg: Patients with multiple myeloma will receive Nivolumab intravenously at 240 mg every two weeks. Infusions will be given over 60 minutes (not bolus or IV push). Patients will continue to receive infusions every two weeks until disease progression or dose limiting toxicity is reached. Radiation therapy: Patients will receive radiation for 5 consecutive days. A dose of 6 Gy x 5 days will be administered. Patients may receive radiotherapy to an additional site at 12 weeks if they have stable disease.
Investigations Platelet count decreased	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Blood and lymphatic system disorders Anemia	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Musculoskeletal and connective tissue disorders Back pain	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.

Other adverse events

Other adverse events
Measure	Nivolumab/Radiotherapy n=5 participants at risk All eligible patients will receive immunotherapy (Nivolumab) plus radiotherapy (6 Gy x 5 fractions) to a targetable lesion. * Nivolumab 240 mg IV starts with the first radiotherapy fraction 240 mg IV every 2 weeks from first radiotherapy fraction until disease prograssion or dose limiting toxicity is reached * Radiotherapy Dose of 6 Gy x 5 days will be given (patients will receive 1 fraction over 5 days for a total of 5 fractions) during the first week of starting Nivolumab Nivolumab 240mg: Patients with multiple myeloma will receive Nivolumab intravenously at 240 mg every two weeks. Infusions will be given over 60 minutes (not bolus or IV push). Patients will continue to receive infusions every two weeks until disease progression or dose limiting toxicity is reached. Radiation therapy: Patients will receive radiation for 5 consecutive days. A dose of 6 Gy x 5 days will be administered. Patients may receive radiotherapy to an additional site at 12 weeks if they have stable disease.
Gastrointestinal disorders Nausea	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Nervous system disorders Peripheral motor neuropathy	40.0% 2/5 • Number of events 2 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Musculoskeletal and connective tissue disorders Back pain	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
General disorders Fatigue	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Musculoskeletal and connective tissue disorders Myalgia	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Gastrointestinal disorders Bloating	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Musculoskeletal and connective tissue disorders bone pain	20.0% 1/5 • Number of events 2 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Gastrointestinal disorders Vomiting	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Gastrointestinal disorders Diarrhea	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Investigations Creatinine increased	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Investigations Alkaline phosphatase increased	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Gastrointestinal disorders Colitis	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Reproductive system and breast disorders pelvic pain	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Investigations Alanine aminotransferase increased	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Investigations Aspartate aminotransferase increased	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.
Metabolism and nutrition disorders Hyperuricemia	20.0% 1/5 • Number of events 1 • Adverse event data is collected from the date of consent until patients withdraw consent. Patients removed from the the study treatment due to disease progression or unacceptable toxicity will be followed until their adverse event returns to baseline values or until study completion, whichever occurs first, unless they withdraw consent. 1 subject withdrew consent before to starting treatment and no AEs were collected, so only 5 subjects were evaluated for AEs.

Additional Information

Dr. Himanshu Nagar

Weill Cornell Medicine

Phone: 212-746-3704

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place