Pembrolizumab and Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma

NCT03267888 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: IRB00097324NCI-2017-01485RAD4106-17P30CA138292
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events

  Greater than grade 2 toxicity will be assessed by Common Terminology Criteria for Adverse Events.

  Up to 12 months after study start

Secondary Outcomes (3)

• Number of Patients Achieving Any Response

  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

  Up to 12 months after study start

• 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

Study Arms (1)

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.

Biological: Pembrolizumab; Radiation: Radiation Therapy

Interventions

Pembrolizumab BIOLOGICAL

Given 200 mg IV.

Also known as: Keytruda, MK-3475

Radiation therapy, pembrolizumab

Radiation Therapy RADIATION

Patients will receive radiotherapy (8 Gy/1 fx) to an extra-osseous site and/or any bony site containing myeloma deposit.

Also known as: Radiotherapy

Radiation therapy, pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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)
• 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

Sponsors & Collaborators

• Emory University: lead
• Merck Sharp & Dohme LLC: collaborator
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• 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.

  PMID: 38797190 DERIVED

Related Links

• peer reviewed journal article

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pembrolizumab; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

• Title: Mohammad K Khan
• Organization: Emory University

m.k.khan@emory.edu

404-778-3473

Study Officials

• Mohammad K. Khan, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 29, 2017
• First Posted: August 30, 2017
• Study Start: May 29, 2018
• Primary Completion: September 2, 2022
• Study Completion: September 2, 2022
• Last Updated: September 4, 2024
• Results First Posted: September 4, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)