Durvalumab and Radiation Therapy in Treating Patients with Solitary Bone Plasmacytoma with Abnormal Cells in Bone Marrow
This phase I trial studies how well durvalumab works with radiation therapy in treating patients with solitary bone plasmacytoma with abnormal cells in their bone marrow. Monoclonal antibodies, such as durvalumab, may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving durvalumab with radiation therapy may kill more tumor cells and work better in treating patients with solitary bone plasmacytoma.
Inclusion Criteria
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Anticipated lifespan greater than 3 month
- Total bilirubin within normal ranges unless associated with hepatobiliary metastases or Gilbert syndrome, then total bilirubin =< 2 x upper limit of normal (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 sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03196401.
PRIMARY OBJECTIVES:
I. To estimate the proportion of patients with solitary bone plasmacytoma and minimal clonal bone marrow plasmacytosis who achieve a stringent complete response (sCR) and/or minimal residual disease (MRD) negativity, defined by undetectable clonal bone marrow plasma cells assessed by immunohistochemistry and multiparameter flow cytometry according to 2016 International Myeloma Working Group (IMWG) criteria on post-treatment bone marrow biopsy and aspirate specimens.
SECONDARY OBJECTIVES:
I. To assess the occurrence and type of toxicity associated with durvalumab use in combination with definitive radiation therapy as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
II. To estimate the time to progression (TTP), as defined as the time from study entry to demonstration of progression of disease (PD) by 2016 IMWG uniform response criteria.
III. To estimate overall survival (OS), defined by time from enrollment to the earlier of death or end of follow-up.
TERTIARY OBJECTIVES:
I. To evaluate the augmentation of post-treatment antigen-specific T cell response as defined by 2-fold increase in intracellular cytokine staining (ICS) assay using stimulation by known tumor associated antigens (CT7, MAGEA3, WT1, SOX2), using stimulation using tumor-associated antigen messenger ribonucleic acid (mRNA)-electroporated autologous dendritic cells.
II. To evaluate T cell receptor diversity and clonality as defined by deep sequencing of T cell receptor using ImmunoSEQ assay performed on paired peripheral blood mononuclear cell samples, with a meaningful result judged as a 2-fold change in either direction.
III. To evaluate changes in clonal populations as defined by data analysis obtained through next generation sequencing of plasmacytoma biopsy specimen, and from paired bone marrow biopsy specimens.
IV. To report descriptively immunophenotyping of T cell, B cell, natural killer (NK) cell, and myeloid cell subsets by flow cytometry and/or immunohistochemistry before, during, and after treatment with durvalumab and radiation therapy.
OUTLINE:
Patients receive durvalumab intravenously (IV) over 1 hour on day 1. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy daily starting on day 1 4-5 times a week for 23-25 treatments.
After completion of study treatment, patients are followed up every 3 months for 36 months.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorAlexander M. Lesokhin
- Primary ID17-269
- Secondary IDsNCI-2017-01457
- ClinicalTrials.gov IDNCT03196401