Multiple MyelomaPhase 2RISE-MNCT03634800
Radiotherapy With Immunotherapy for Systemic Effect in Myeloma (RISE-M)
A Phase 2 study testing Nivolumab 240mg and Radiation therapy in people with Multiple Myeloma, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
Eligible patients have multiple myeloma with measurable disease in the blood and a targetable soft tissue or bony lesion with radiotherapy. All eligible patients will receive immunotherapy (Nivolumab) plus radiotherapy, 6 Gy x 5 fractions, to a targetable lesion. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Nivolumab 240mg and Radiation therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Oct 2018to 16 Jan 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is, in the investigator's opinion, willing and able to comply with the protocol requirements.
- Subject has given voluntary written informed consent before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care.
- Must have received 2 consecutive cycles of systemic myeloma therapy.
- Documented refractory or relapsed and refractory (R/R) multiple myeloma
- patients had less than minimal response, or had achieved at least a minimal response to previous treatment, but progressed within 6 months
- patients must have failed, be intolerant or are ineligible to treatment with an IMiD, proteasome inhibitor and anti-CD38 agent
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- Targetable plasmacytoma, either intra-or extramedullary that is visualized on imaging (PET/CT or MRI) and is causing symptoms (eg. pain, neurological compromise) or potential to cause symptom as per clinician's judgement; and measurable disease at screening, defined as one or more of the following:
- Serum IgG, IgA, or IgM M-protein ≥ 0.5 g/dL
- Urine M-Protein ≥ 200 mg excreted in a 24-hour collection sample
- Involved serum free light chain (sFLC) > 100 mg/L provided the FLC ratio is abnormal
- Males and Females at least 18 years or legal age of consent per local regulations.
- Women of childbearing potential (WOCBP) must have two negative serum or urine pregnancy tests (minimum sensitivity 25 mIU/mL or equivalent units of HCG). One 10-14 days prior to start of the study drug and one within 24 hours prior to the start of study drug.
- Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly.
- No condition which would cause unacceptable risk.
Who cannot join
- Subjects with solitary bone or extramedullary plasmacytoma as the only evidence of plasm cell dyscrasia.
- Subjects with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), Waldenstrom's macroglobulinemia, or POEMS syndrome (plasma cell dyscrasia with poly neuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
- Subjects with active plasma cell leukemia (defined as either 20% of peripheral blood white blood cell count comprised of plasma/CD138+ cells or an absolute plasma cell count of 2 x 109/L).
- Subjects within 100 days of stem cell transplantation.
- Subjects within 4 weeks of surgery, unless cleared by surgeon.
- Women who are of childbearing potential not complying to the above described contraceptive measures or are breastfeeding, and sexually active fertile men whose partners are WOCBP if they are not complying to the above described contraceptive measures.
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- Any uncontrolled or severe cardiovascular or pulmonary disease determined by the investigator, including:
- NYHA functional classification III or IV, congestive heart failure, unstable or poorly controlled angina, uncontrolled hypertension, arrhythmia, or myocardial infarction in the past 12 months
- Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
- Active infection or know HBV/HCV/HIV.
- Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of initiation of study drug. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
- Previous radiotherapy to the area of the target area.
- Prior exposure to immunotherapy.
Trial locations and contacts
1 site in 1 country.
About this study
Eligible patients have multiple myeloma with measurable disease in the blood and a targetable soft tissue or bony lesion with radiotherapy. All eligible patients will receive immunotherapy (Nivolumab) plus radiotherapy, 6 Gy x 5 fractions, to a targetable lesion. Immunotherapy treatment starts with the first radiotherapy fraction. Nivolumab will be given every 2 weeks. Patients will have specified laboratory values measured bi-monthly and evaluated for response at 12 weeks as defined by International Myeloma Working Group Criteria. Patients will continue to receive their respective immunotherapy until disease progression or dose limiting toxicity is reached.
Read the detailed description
All eligible patients will receive immunotherapy (Nivolumab) plus radiotherapy, 6 Gy x 5 fractions, to a targetable lesion. Immunotherapy treatment starts with the first radiotherapy fraction. Nivolumab will be given every 2 weeks. Patients will have specified laboratory values measured bi-monthly and evaluated for response at 12 weeks as defined by International Myeloma Working Group Criteria. Patients will continue to receive their respective immunotherapy until disease progression or dose limiting toxicity is reached.
- Conditions
- Multiple Myeloma
- Being tested
- Nivolumab 240mg, Radiation therapy
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab 240mgDrug
Also called Immunotherapy
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 therapyRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| nivolumab/radiotherapy | Experimental | 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 Receives: Drug: Nivolumab 240mg; Radiation: Radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Determine Overall Response at 12 Weeks Using International Myeloma Working Group (IMWG) Criteria in Patients Will be Measured
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.
Measured: 12 weeks
Secondary outcomes (2)
To Determine the Median Progression Free Survival (PFS) Will be Assessed in Patients Treated With Immunotherapy and Radiotherapy.
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.
Measured: through study completion
To Determine the Median Overall Survival for Patients Treated With Immunotherapy and Radiotherapy Will be Assessed.
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.
Measured: through study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2018
- Study start23 Oct 2018
- Primary completion9 Jan 2020
- Study completion16 Jan 2020
Why it stopped: Lack of patient accruals.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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. 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.
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Adriana Rossi, M.D., Principal investigator, Weill Cornell Medicine - New York Presbyterian HospitalHimanshu Nagar, M.D., Principal investigator, Weill Cornell Medicine - New York Presbyterian Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03634800
- Sponsor's protocol ID
- 1612017831
- Acronym
- RISE-M
- Status last verified
- Jul 2021
- First submitted
- 14 Aug 2018
- Last updated
- 5 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radiotherapy With Immunotherapy for Systemic Effect in Myeloma (RISE-M)
- ClinicalTrials.gov ID
- NCT03634800
- Acronym / sponsor ID
- RISE-M / 1612017831
- Conditions
- Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of patient accruals.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Study start
- 23 Oct 2018 (actual)
- Primary completion
- 9 Jan 2020 (actual)
- Study completion
- 16 Jan 2020 (actual)
- First posted
- 16 Aug 2018 (actual)
- Results
- Posted 5 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Eligible patients have multiple myeloma with measurable disease in the blood and a targetable soft tissue or bony lesion with radiotherapy. All eligible patients will receive immunotherapy (Nivolumab) plus radiotherapy, 6 Gy x 5 fractions, to a targetable lesion. Immunotherapy treatment starts with the first radiotherapy fraction. Nivolumab will be given every 2 weeks. Patients will have specified laboratory values measured bi-monthly and evaluated for response at 12 weeks as defined by International Myeloma Working Group Criteria. Patients will continue to receive their respective immunotherapy until disease progression or dose limiting toxicity is reached.
Detailed description
All eligible patients will receive immunotherapy (Nivolumab) plus radiotherapy, 6 Gy x 5 fractions, to a targetable lesion. Immunotherapy treatment starts with the first radiotherapy fraction. Nivolumab will be given every 2 weeks. Patients will have specified laboratory values measured bi-monthly and evaluated for response at 12 weeks as defined by International Myeloma Working Group Criteria. Patients will continue to receive their respective immunotherapy until disease progression or dose limiting toxicity is reached.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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. 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.
| Arm | Type | Receives |
|---|---|---|
| nivolumab/radiotherapy | Experimental | Drug: Nivolumab 240mg, Radiation: Radiation therapyAll 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 |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Subject is, in the investigator's opinion, willing and able to comply with the protocol requirements.
- Subject has given voluntary written informed consent before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care.
- Must have received 2 consecutive cycles of systemic myeloma therapy.
- Documented refractory or relapsed and refractory (R/R) multiple myeloma
- Targetable plasmacytoma, either intra-or extramedullary that is visualized on imaging (PET/CT or MRI) and is causing symptoms (eg. pain, neurological compromise) or potential to cause symptom as per clinician's judgement; and measurable disease at screening, defined as one or more of the following:
Key exclusion criteria (14 listed)
- Subjects with solitary bone or extramedullary plasmacytoma as the only evidence of plasm cell dyscrasia.
- Subjects with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), Waldenstrom's macroglobulinemia, or POEMS syndrome (plasma cell dyscrasia with poly neuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
- Subjects with active plasma cell leukemia (defined as either 20% of peripheral blood white blood cell count comprised of plasma/CD138+ cells or an absolute plasma cell count of 2 x 109/L).
- Subjects within 100 days of stem cell transplantation.
- Subjects within 4 weeks of surgery, unless cleared by surgeon.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumab 240mgAlso: ImmunotherapyPatients 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. | Drug | nivolumab/radiotherapy |
| Radiation therapyPatients 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. | Radiation | nivolumab/radiotherapy |
Primary outcome
To Determine Overall Response at 12 Weeks Using International Myeloma Working Group (IMWG) Criteria in Patients Will be Measured
Time frame: 12 weeks
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.
2 secondary outcomes
To Determine the Median Progression Free Survival (PFS) Will be Assessed in Patients Treated With Immunotherapy and Radiotherapy.
Time frame: through study completion
To Determine the Median Overall Survival for Patients Treated With Immunotherapy and Radiotherapy Will be Assessed.
Time frame: through study completion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adriana Rossi, M.D. principal investigator
Weill Cornell Medicine - New York Presbyterian Hospital
Himanshu Nagar, M.D. principal investigator
Weill Cornell Medicine - New York Presbyterian Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab 240mg and Radiation therapy in people with Multiple Myeloma, run by Weill Medical College of Cornell University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To Determine Overall Response at 12 Weeks Using International Myeloma Working Group (IMWG) Criteria in Patients Will be Measured (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2021.