A Study of Durvalumab (Anti-PDL1) Plus Radiation Therapy for the Treatment of Solitary Bone Plasmacytoma

A Pilot Study to Evaluate for the Abscopal Effect of Durvalumab (Anti-PD-L1) in Combination With Definitive Radiation Therapy in Solitary Bone Plasmacytoma With Limited Clonal Bone Marrow Plasmacytosis

This study is being done to evaluate whether the combination of immune therapy and radiation therapy to plasmacytoma that can stimulate the immune system to attack and eliminate the abnormal cells in the bone marrow and perhaps delay or prevent the cancer from worsening. This study will evaluate whether the immune system responds to the combination of radiation with immunotherapy. It is possible that that the combination of immune therapy and radiation may not make any difference in whether or not the patient will develop multiple myeloma in the future.

Study Overview

• Status: Withdrawn
• Conditions: Solitary Bone Plasmacytoma
• Intervention / Treatment: Drug: Durvalumab; Radiation: Radiation therapy

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge
    • Middletown, New Jersey, United States, 07748
      • Memoral Sloan Kettering Monmouth
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States, 11570
      • Memorial Sloan Kettering Rockville Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years
• Histologically confirmed plasmacytoma amenable for biopsy
• Detectable clonal bone marrow plasma cells by multicolor flow cytometry and less than 10% clonal plasma cells in a bone marrow biopsy by immunohistochemistry, morphology, or flow cytometry.
• Clinically safe to delay radiation for at least 2 weeks.
• ECOG performance status of 0-1.
• Anticipated lifespan greater than 3 month.

• Adequate organ function, as defined below:

  • Total bilirubin within normal ranges unless associated with hepatobiliary metastases or Gilbert syndrome, then total bilirubin ≤ 2 x ULN
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
  • Creatinine ≤ 2.0 mg/dL
• Able and willing to give valid written informed consent.

Exclusion Criteria:

• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener's syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves' disease; rheumatoid arthritis; hypophysitis, uveitis; etc) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: subjects with vitiligo or alopecia; subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement; or subjects with psoriasis not requiring systemic treatment.
• Current or prior use of immunosuppressive medication within 14 days prior to first dose of durvalumab. The following are exceptions to this criterion: intranasal, inhaled, topical or local steroid injections (eg. intra-articular injection); steroids as premedication for hypersensitivity reactions; systemic corticosteroid at physiologic doses not to exceed 10mg/day of prednisone or equivalent.
• Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or evidence of active hepatitis B virus (HBV).
• History of hypersensitivity to durvalumab or any excipient
• History of hypersensitivity to the combination or comparator agent (If applicable) Receipt of live attenuated vaccination within 30 days prior the first dose of durvalumab.
• Female subjects who are pregnant, breast-feeding or female patients of reproductive potential who are not employing an effective method of birth control from starting dose of durvalumab (Cycle 1 Day 1), including dosing interruptions through 90 days after receipt of the last dose of durvalumab. Refrain from egg cell donation while taking durvalumab and for at least 90 days after the last dose of durvalumab.
• Male subjects who are not employing an effective method of birth control from starting dose of durvalumab (Cycle 1 Day 1), including dosing interruptions through 90 days after receipt of the last dose of durvalumab. Refrain from sperm donation while taking durvalumab and for at least 90 days after the last dose of durvalumab.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Durvalumab Plus Radiation Therapy; Durvalumab (1500mg administered intravenously every 28 days), concurrently with definitive radiation therapy to the solitary bone plasmacytoma to start within 14 days of the first dose of durvalumab.	Drug: Durvalumab; durvalumab 1500mg administered intravenously every 28 days, for a total of six doses; Other Names: (MEDI4736); Radiation: Radiation therapy; concurrent definitive radiation therapy to the bone plasmacytoma initiated within two weeks of starting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response assessment	Disease assessments are made according to IMWG criteria including criteria for minimal residual disease	up to 36 months from start of cycle 1

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Celgene Corporation
• Investigators: Principal Investigator: Alexander Lesokhin, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2017
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): June 1, 2020

Study Registration Dates

• First Submitted: June 21, 2017
• First Submitted That Met QC Criteria: June 21, 2017
• First Posted (Actual): June 22, 2017

Study Record Updates

• Last Update Posted (Actual): August 3, 2018
• Last Update Submitted That Met QC Criteria: August 2, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Radiation Therapy; MEDI4736; Durvalumb; Clonal Bone Marrow Plasmacytosis; 17-269
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Plasmacytoma; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: 17-269

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No