ISS Stage I Plasma Cell MyelomaPhase 1/2NCT03267888
Pembrolizumab and Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma
A Phase 1/2 study testing Pembrolizumab and Radiation Therapy in people with ISS Stage I Plasma Cell Myeloma and ISS Stage II Plasma Cell Myeloma, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ISS Stage I Plasma Cell Myeloma, ISS Stage II Plasma Cell Myeloma, ISS Stage III Plasma Cell Myeloma
- What is being tested?
- Pembrolizumab 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
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 29 May 2018to 2 Sep 2022
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- Previous anti-programmed cell death protein 1 (PD1) or anti-PD-L1
- Solitary plasmacytoma
- Smoldering (asymptomatic) multiple myeloma
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency
- Known history of active TB (Bacillus tuberculosis)
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- Hypersensitivity to pembrolizumab or any of its recipients
- Known additional malignancy that is progressing or requires active treatment (exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin)
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
- Known history of, or any evidence of active, non-infectious pneumonitis
- Active infection requiring systemic therapy
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
- Has received a live vaccine within 30 days of planned start of study therapy; NOTE: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
- Patients requiring radiation for CNS diseases are excluded (CNS defined as brain soft tissue/intra parenchymal metastases within the gray and white matter of the brain and/or for cerebrospinal fluid [CSF] disseminated disease, including leptomeningeal carcinomatous disease)
- Has a history of allogeneic stem cell transplantation
Trial locations and contacts
1 site in 1 country.
United States1 site
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322
About this study
Official title: Pilot Study of Pembrolizumab and Single-Fraction, Low-Dose, Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- Conditions
- ISS Stage I Plasma Cell Myeloma, ISS Stage II Plasma Cell Myeloma, ISS Stage III Plasma Cell Myeloma, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- Being tested
- Pembrolizumab, 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.
PembrolizumabBiological
Also called Keytruda, MK-3475
Given 200 mg IV.
Radiation TherapyRadiation
Also called Radiotherapy
Patients will receive radiotherapy (8 Gy/1 fx) to an extra-osseous site and/or any bony site containing myeloma deposit.
| Study group | Role | What they receive |
|---|---|---|
| Radiation therapy, pembrolizumab | Experimental | 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. Receives: Biological: Pembrolizumab; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
Greater than grade 2 toxicity will be assessed by Common Terminology Criteria for Adverse Events.
Measured: Up to 12 months after study start
Secondary outcomes (3)
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.
Measured: Up to 12 months after study start
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.
Measured: Up to 12 months after study start
Overall Survival
Will be estimated using the Kaplan-Meier product-limit method.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2017
- Study start29 May 2018
- Primary completion2 Sep 2022
- Study completion2 Sep 2022
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ISS Stage I Plasma Cell MyelomaStudies of the same condition, open and under way.
- More trials run by Emory 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, National Cancer Institute (NCI), National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Mohammad K. Khan, Emory University
- Investigators
- Mohammad K. Khan, MD, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03267888
- Sponsor's protocol ID
- IRB00097324
- Other IDs
- NCI-2017-01485, RAD4106-17, P30CA138292
- Status last verified
- Aug 2024
- First submitted
- 29 Aug 2017
- Last updated
- 4 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Khan MK, Nasti TH, Qian JY, Kleber TJ, Switchenko JM, Kaufman JL, Nooka AJ, Dhodapkar MV, Buchwald ZS, Obiekwe D, Lonial S, Ahmed R. Pembrolizumab and low-dose, single-fraction radiotherapy for patients with relapsed or refractory multiple myeloma: a prospective, single-centre, single-group, open-label, phase 2 pilot trial in the USA. Lancet Haematol. 2024 Jul;11(7):e510-e520. doi: 10.1016/S2352-3026(24)00105-4. Epub 2024 May 23.
PubMed 38797190
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Pembrolizumab and Single-Fraction, Low-Dose, Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT03267888
- Acronym / sponsor ID
- IRB00097324
- Conditions
- ISS Stage I Plasma Cell Myeloma, ISS Stage II Plasma Cell Myeloma, ISS Stage III Plasma Cell Myeloma, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, National Cancer Institute (NCI), National Institutes of Health (NIH)
- Study start
- 29 May 2018 (actual)
- Primary completion
- 2 Sep 2022 (actual)
- Study completion
- 2 Sep 2022 (actual)
- First posted
- 30 Aug 2017 (actual)
- Results
- Posted 4 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Radiation therapy, pembrolizumab | Experimental | Biological: Pembrolizumab, Radiation: Radiation TherapyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (17 listed)
- Previous anti-programmed cell death protein 1 (PD1) or anti-PD-L1
- Solitary plasmacytoma
- Smoldering (asymptomatic) multiple myeloma
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency
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 |
|---|---|---|
| PembrolizumabAlso: Keytruda, MK-3475Given 200 mg IV. | Biological | Radiation therapy, pembrolizumab |
| Radiation TherapyAlso: RadiotherapyPatients will receive radiotherapy (8 Gy/1 fx) to an extra-osseous site and/or any bony site containing myeloma deposit. | Radiation | Radiation therapy, pembrolizumab |
Primary outcome
Number of Participants With Adverse Events
Time frame: Up to 12 months after study start
Greater than grade 2 toxicity will be assessed by Common Terminology Criteria for Adverse Events.
3 secondary outcomes
Number of Patients Achieving Any Response
Time frame: Up to 12 months after study start
Number of Participants Who Showed an Overall Response to Treatment Based on Baseline Changes on Positron Emission to Positron Emission Tomography/Computed Tomography
Time frame: Up to 12 months after study start
Overall Survival
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38797190Khan MK, Nasti TH, Qian JY, Kleber TJ, Switchenko JM, Kaufman JL, Nooka AJ, Dhodapkar MV, Buchwald ZS, Obiekwe D, Lonial S, Ahmed R. Pembrolizumab and low-dose, single-fraction radiotherapy for patients with relapsed or refractory multiple myeloma: a prospective, single-centre, single-group, open-label, phase 2 pilot trial in the USA. Lancet Haematol. 2024 Jul;11(7):e510-e520. doi: 10.1016/S2352-3026(24)00105-4. Epub 2024 May 23.
- peer reviewed journal articleLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Mohammad K. Khan, MD, PhD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pembrolizumab and Radiation Therapy in people with ISS Stage I Plasma Cell Myeloma and ISS Stage II Plasma Cell Myeloma, run by Emory 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 12 inclusion and 17 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: finished, as of the sponsor's last update on 4 Sep 2024. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 4 Sep 2024). 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?
Number of Participants With Adverse Events (time frame: Up to 12 months after study start). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03267888, which also lists 1 linked publication.
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 4 Sep 2024.