Avelumab in Combination With Hypofractionated Radiotherapy in Patients With Relapsed Refractory Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT03910439|
Recruitment Status : Recruiting
First Posted : April 10, 2019
Last Update Posted : October 15, 2019
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.
To see if avelumab given with radiation treatment helps treat multiple myeloma. Also to see if giving the treatments together is safe.
People ages 18 and older with multiple myeloma that has come back after treatment and has spread to other parts of the body
Participants will be screened with:
Blood, urine, and heart tests
Possible tumor biopsy
Bone marrow testing: A needle will be stuck into the participant s hipbone to take out a small amount of marrow.
PET/CT scan and MRI: Participants will lie in a machine that takes pictures of the body.
Participants will get avelumab through an 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....
|Condition or disease||Intervention/treatment||Phase|
|Myeloma-Multiple||Biological: Avelumab Radiation: External beam radiotherapy||Phase 2|
- 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.
- To assess the response rate of avelumab in combination with XRT (BavXRT) in RRMM patients with plasmacytomas or lytic lesions
- 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-CD38 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.
- Treatment will consist of a 4-week lead-in with avelumab, followed by concurrent XRT 5Gy 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- evalutions at at time of response [i.e., CR/PD]).
- Bone marrow biopsies will be evaluated for PD-1/L1 expression, and B and T cell subsets using 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Pilot Study of Avelumab in Combination With Hypofractionated Radiotherapy in Patients With Relapsed Refractory Multiple Myeloma|
|Estimated Study Start Date :||October 18, 2019|
|Estimated Primary Completion Date :||July 1, 2023|
|Estimated Study Completion Date :||July 1, 2024|
Avelumab 800 mg IV every two weeks in combination with radiation therapy
Avelumab 800 mg IV over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle
Radiation: External beam radiotherapy
5 Gy per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy
- Overall response rate (ORR) [ Time Frame: every 6-8 weeks ]The fraction of patients who experience a partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) per IMWG 2016 criteria.
- Complete Response (CR) rate and Minimal Residual Disease (MRD) negative CR rate [ Time Frame: every 6-8 weeks ]the fraction of patients who experience a CR or sCR using the study treatment
- Reductions in bone marrow (BM) and peripheral blood (PD) plasmacytosis [ Time Frame: every 6-8 weeks ]the fraction of patients who experience an MRDnegCR using the study treatment
- Radiographic reduction in size, and/or FDG avidity (PET/CT) of extramedullary lesio [ Time Frame: every 6-8 weeks ]percent change in plasma cells in the PB and BM from baseline
- Radiographic reduction in size, and/or FDG avidity (PET/CT) of non-irradiated extramedullary lesions (abscopal effect) [ Time Frame: every 6-8 weeks ]percent reduction of size, and/or FDG avidity, radiographicaly, of extramedullary lesions compared to baseline
- Progression-free survival (PFS) [ Time Frame: every 6-8 weeks ]determined using the Kaplan- Meier method, considering those who progress or die without progression as failures, and censoring thosewho do not.
- Overall survival (OS) [ Time Frame: ongoing ]will be determined using the Kaplan-Meier method
- All Grade, Grade 3-4, and serious adverse events [ Time Frame: ongoing ]overall tolerability in terms of adverse events will be evaluated with descriptive statistics to determine the safety of receiving avelumabin the context of irradiation
- ORR post cycle 1 (prior to XRT) [ Time Frame: 4 weeks ]a milestone ORR at start of cycle 2 will be calculated as above to determine ORR of avelumab monotherapy after 1 cycle of therapy
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): NCT03910439
|Contact: Maureen E Edgerly, R.N.||(240) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Dickran G Kazandjian, M.D.||National Cancer Institute (NCI)|