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

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ClinicalTrials.gov Identifier: NCT03267888
Recruitment Status : Recruiting
First Posted : August 30, 2017
Last Update Posted : February 11, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Mohammad K. Khan, Emory University

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.

Condition or disease Intervention/treatment Phase
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 Biological: Pembrolizumab Radiation: Radiation Therapy Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Pembrolizumab and Single-Fraction, Low-Dose, Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : May 29, 2018
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : May 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: 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.
Biological: Pembrolizumab
Given 200 mg/kg IV.
Other Names:
  • Keytruda
  • MK-3475

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




Primary Outcome Measures :
  1. Incidence of 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. Proportion adverse events will be reported.


Secondary Outcome Measures :
  1. Number of patients achieving any response [ Time Frame: Up to 12 months after study start ]
    According to International Myeloma Working Group (IMWG) criteria.

  2. Overall response based on baseline changes on positron emission to positron emission tomography/computed tomography [ Time Frame: Up to 12 months after study start ]
    Will be defined using International IMWG criteria.

  3. 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 ]
    Will be estimated using the Kaplan-Meier product-limit method.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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); 6 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03267888


Contacts
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Contact: Mohammad K. Khan, MD, PhD 404-778-3473 m.k.khan@emory.edu
Contact: Jonathan Kaufman, MD jlkaufm@emory.edu

Locations
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United States, Georgia
Emory University/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Stacey Worrell    404-778-4206    stacey.worrell@emory.edu   
Contact: Giesla Rodgers    404-778-5162    grodg01@emory.edu   
Sponsors and Collaborators
Emory University
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Mohammad K. Khan, MD, PhD Emory University

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Responsible Party: Mohammad K. Khan, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT03267888     History of Changes
Other Study ID Numbers: IRB00097324
NCI-2017-01485 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RAD4106-17 ( Other Identifier: Emory University/Winship Cancer Institute )
First Posted: August 30, 2017    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents