Clinical Trials /

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

NCT03267888

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma
  • Official Title: Pilot Study of Pembrolizumab and Single-Fraction, Low-Dose, Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: IRB00097324
  • SECONDARY ID: NCI-2017-01485
  • SECONDARY ID: RAD4106-17
  • NCT ID: NCT03267888

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

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, MK-3475Radiation therapy, pembrolizumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Radiation therapy, pembrolizumabExperimentalPatients 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

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 12 months after study start
Safety Issue:
Description:Greater than grade 2 toxicity will be assessed by Common Terminology Criteria for Adverse Events. Proportion adverse events will be reported.

Secondary Outcome Measures

Measure:Number of patients achieving any response
Time Frame:Up to 12 months after study start
Safety Issue:
Description:According to International Myeloma Working Group (IMWG) criteria.
Measure:Overall response based on baseline changes on positron emission to positron emission tomography/computed tomography
Time Frame:Up to 12 months after study start
Safety Issue:
Description:Will be defined using International IMWG criteria.
Measure: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
Safety Issue:
Description:Will be estimated using the Kaplan-Meier product-limit method.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Emory University

Last Updated

February 8, 2019