ISS Stage III Plasma Cell Myeloma, ISS Stage II Plasma Cell Myeloma, ISS Stage I Plasma Cell Myeloma, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
Conditions
Brief summary
This pilot clinical trial studies the side effects of pembrolizumab and radiation therapy in treating patients with stage I-III multiple myeloma that has come back after a period of improvement or that does not respond to treatment. Monoclonal antibodies, such as pembrolizumab, may block cancer growth in different ways by targeting certain cells. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving pembrolizumab and radiation therapy may work better in treating patients with stage I-III multiple myeloma.
Detailed description
PRIMARY OBJECTIVE: I. To evaluate the safety of concurrent single/low dose radiation therapy (radiotherapy) (8 Gy/1fx) in combination with pembrolizumab in relapsed or refractory myeloma patients. SECONDARY OBJECTIVES: I. To characterize late toxicity (Common Terminology Criteria for Adverse Events \[CTCAE\] \> grade 2 toxicity at 6 and 12 months) and the effect of radiation in combination with pembrolizumab on systemic response rates using international myeloma working group (IMWG) uniform response criteria for multiple myeloma at 6 months and 12 months. II. To assess changes in positron emission tomography/computed tomography (PET/CT) as a result of combining pembrolizumab and radiotherapy at 6 months and 12 months. OUTLINE: Patients undergo radiation therapy on day 1. Patients also receive pembrolizumab intravenously (IV) over 30 minutes on day 2 or 3. Courses with pembrolizumab repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks thereafter.
Interventions
BIOLOGICALPembrolizumab
Given 200 mg IV.
RADIATIONRadiation Therapy
Patients will receive radiotherapy (8 Gy/1 fx) to an extra-osseous site and/or any bony site containing myeloma deposit.
Sponsors
Merck Sharp & Dohme LLC
National Cancer Institute (NCI)
National Institutes of Health (NIH)
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* International Staging System (ISS) stage I-III multiple myeloma that has progressive, relapsed, or refractory disease * Able to give informed consent * Eastern Cooperative Oncology Group (ECOG) 0-1 * Relapsed and/or refractory myeloma; there is no minimum or maximum number of previous therapies that a patient may have received previously before being put on the current trial * ≥ 1 osseous and/or extra-osseous lesion that can be radiated * Candidate for pembrolizumab (as determined by physician, and adequate organ function) * Candidate for radiotherapy (as determined by treatment physician); these patients can have symptomatic disease and/or asymptomatic disease; a minimum of one site of radiation is required to any osseous and/or any extra-osseous disease; radiation to any bony parts of the head and neck, skull, spine, ribs, and/or extremities are allowed; radiation to any bony part for documented lytic disease is allowed; radiation to any soft tissue plasmacytoma (including osseous and extra-osseous plasmacytoma) is allowed; the only
Exclusion criteria
for radiation, is central nervous system (CNS) metastases * Measurable myeloma disease (urine protein \> 200 mg in 24 hours \[hr\] urine collection, serum free light chain ratio \> 100 with an abnormal k/l ratio, serum M protein \> 0.5 g/dl); 12 of the 24 patients do not have to have measurable disease * Negative urine pregnancy test within 2 weeks for female subjects; female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year * Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy * Abstinence is acceptable, if this is the usual life style and preferred contraception for the patient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Up to 12 months after study start | Greater than grade 2 toxicity will be assessed by Common Terminology Criteria for Adverse Events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Achieving Any Response | Up to 12 months after study start | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR according to International Myeloma Working Group (IMWG) criteria. |
| Number of Participants Who Showed an Overall Response to Treatment Based on Baseline Changes on Positron Emission to Positron Emission Tomography/Computed Tomography | Up to 12 months after study start | Will be defined using International IMWG criteria. |
| Overall Survival | From first treatment on course 1, day 1 to the earlier of date of death and/or last follow up, assessed up to 12 months | Will be estimated using the Kaplan-Meier product-limit method. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiation Therapy, Pembrolizumab Patients undergo radiation therapy on day 1. Patients also receive pembrolizumab IV over 30 minutes on day 2 or 3. Courses with pembrolizumab repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Pembrolizumab: Given 200 mg/kg IV.
Radiation Therapy: Patients will receive radiotherapy (8 Gy/1 fx) to an extra-osseous site and/or any bony site containing myeloma deposit. | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Radiation Therapy, Pembrolizumab |
|---|---|
| Age, Continuous | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 25 |
| other Total, other adverse events | 8 / 25 |
| serious Total, serious adverse events | 1 / 25 |
Outcome results
Primary
Number of Participants With Adverse Events
Greater than grade 2 toxicity will be assessed by Common Terminology Criteria for Adverse Events.
Time frame: Up to 12 months after study start
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation Therapy, Pembrolizumab | Number of Participants With Adverse Events | 8 Participants |
Secondary
Number of Participants Who Showed an Overall Response to Treatment Based on Baseline Changes on Positron Emission to Positron Emission Tomography/Computed Tomography
Will be defined using International IMWG criteria.
Time frame: Up to 12 months after study start
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiation Therapy, Pembrolizumab | Number of Participants Who Showed an Overall Response to Treatment Based on Baseline Changes on Positron Emission to Positron Emission Tomography/Computed Tomography | 20 participants |
Secondary
Number of Patients Achieving Any Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR according to International Myeloma Working Group (IMWG) criteria.
Time frame: Up to 12 months after study start
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation Therapy, Pembrolizumab | Number of Patients Achieving Any Response | 8 Participants |
Secondary
Overall Survival
Will be estimated using the Kaplan-Meier product-limit method.
Time frame: From first treatment on course 1, day 1 to the earlier of date of death and/or last follow up, assessed up to 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiation Therapy, Pembrolizumab | Overall Survival | 15 participants |