Avelumab in Combination With Hypofractionated Radiotherapy in Patients With Relapsed Refractory Multiple Myeloma

Myeloma-Multiple Clinical Trial

Official title: A Phase II Pilot Study of Avelumab in Combination With Hypofractionated Radiotherapy in Patients With Relapsed Refractory Multiple Myeloma

Status Terminated

Clinical Trial Summary

Background:

Multiple myeloma is a cancer that forms from plasma cells which normally produce important immune response antibodies. It cannot be cured. Researchers hope the combination of radiation combined with the drug avelumab causes the immune system to kill myeloma cells more effectively.

Objective:

To see if avelumab given with radiation treatment helps treat multiple myeloma. Also to see if giving the treatments together is safe.

Eligibility:

People ages 18 and older with multiple myeloma that has come back after treatment and has spread to other parts of the body

Design:

Participants will be screened with:

Medical history

Physical exam

Blood, urine, and heart tests

Possible tumor biopsy

Bone marrow testing: A needle will be stuck into the participants hipbone to take out a small amount of marrow.

Positron emission tomography (PET)/Computed tomography (CT) scan and magnetic resonance imaging (MRI): Participants will lie in a machine that takes pictures of the body.

Participants will get avelumab through an intravenous (IV). An IV is a small plastic tube put into an arm vein. They will get avelumab every 2 weeks for 2 doses. Then they will get radiation each day for 5 days. They will continue to get avelumab every 2 weeks as long as they do not have bad side effects and the treatment is helping their disease.

Participants will have blood and urine tests, bone marrow biopsies, scans, and X-rays repeated during the study.

Participants will have a follow-up visit 30 days after their last treatment dose. Then they will have visits every 3-6 months for up to 5 years....

Clinical Trial Description

Background:

• Multiple Myeloma (MM) is a hematologic neoplasm of the plasma cells defined by an M- protein greater than or equal to 3.0 g/dL or bone marrow plasma cells greater than or equal to 10% and presence of end-organ disease.

• Although significant advances in treatment have been made in the past decade, MM remains incurable with median survivals of 5-8 years.

• While therapeutic strides have been made with approvals of immunomodulatory drugs (IMiDs), proteasome inhibitors, and monoclonal antibodies, treatment of relapsed refractory MM (RRMM) remains an unmet need for patients who have exhausted available therapies.

• Extramedullary plasmacytomas arising either from focal bone involvement or from hematogenous spread occur in 7-18% of newly diagnosed MM (NDMM) with an additional 6-20% in RRMM.

• Immune checkpoint inhibitors are being evaluated in combination regimens and evidence exists that radiation therapy (XRT) may synergize with immune checkpoint inhibitors.

Objectives:

• To assess the response rate of avelumab in combination with XRT (BavXRT) in RRMM patients with plasmacytomas or lytic lesions

Eligibility:

• Patients must have previously treated RRMM refractory to, ineligible for, or intolerant of available therapeutic regimens known to provide clinical benefit (e.g, immunomodulatory [IMiD], proteasome inhibitor, and anti-cluster of differentiation (CD)38 monoclonal antibody-based treatments).

• Presence of greater than or equal to 1 extramedullary plasmacytoma and/or lytic lesion amenable to XRT

• Age greater than or equal to 18 years

• Adequate organ function, and without serious comorbidity or disease (e.g., autoimmune disease), that would preclude concurrent systemic treatment or radiotherapy.

Design:

• Treatment will consist of a 4-week lead-in with avelumab, followed by concurrent XRT 5 gray (Gy) x 5 days). Monotherapy avelumab will continue indefinitely until progressive disease (PD) or unacceptable toxicity; 28-day cycles.

• Routine safety and MM-specific clinical labs will be assessed. Additional research bloods will be collected for evaluating immune-subsets, endosomes, and peripheral blood T cell repertoire prior to and following treatment (lead-in and prior to XRT, at disease re- evaluations at at time of response [i.e., complete remission (CR)/progressive disease (PD)]).

• Bone marrow biopsies will be evaluated for Programmed death-ligand 1 (PD-1)/ligand 1 (L1) expression, and B and T cell subsets using immunohistochemistry (IHC). Flow cytometry will also be used to evaluate stimulatory and inhibitory immune subsets along with endosomes. Standard clinical histopathology and flow cytometry will also be evaluated.

• Single arm, Simon minimax two-stage phase II trial design. The first stage will enroll 13 patients; if futility is not met, second stage will enroll another 14 patients to define the response rate to BavXRT in this population. Early stopping rules for safety will also be applied. ;

Related Conditions & MeSH terms

• Multiple Myeloma
• Myeloma, Multiple
• Myeloma-Multiple
• Neoplasms, Plasma Cell

• NCT number: NCT03910439
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 2
• Start date: October 17, 2019
• Completion date: November 4, 2020