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

NCT03910439 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 19007819-C-0078
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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....

Conditions

Myeloma, Multiple; Myeloma-Multiple

Keywords

Monoclonal Antibody; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR is defined as participants who experience a partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) per International Myeloma Working Group Criteria (IMWG) 2016 criteria. Complete Response is defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates. Stringent Complete Response is defined as complete response as noted previously plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow biopsy by immune-histochemistry. Partial Response is ≥50% reduction of serum M-protein plus reduction in 24 hour(h) urinary M-protein by ≥90% or to \<200 mg per 24 h. Very Good Partial Response is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level \<100 mg per 24 h.

  up to end of study, an average of 11 months

Secondary Outcomes (9)

• Fraction of Participants Who Experience a Complete Response (CR) or Stringent Complete Response (sCR) Using the Study Treatment

  up to end of study for individual patient, an average of 11 months

• Fraction of Participants Who Experience a Minimal Residual Disease Negative (MRDneg)Complete Response (CR) Using the Study Treatment

  up to up to end of study for individual patient, an average of 11 months

• Percent Change in Aberrant Circulating Plasma Cells in the Peripheral Blood (PB) and Bone Marrow (BM) From Baseline

  Baseline and up to end of study for individual patient, an average of 11 months

• Percent Reduction in Size of On-irradiated Extramedullary Lesions

  end of study

• Fluorodeoxyglucose (FDG) Avidity Positron-Emission Tomography/Computed Tomography (PET/CT) of Non-irradiated Extramedullary Lesions (Abscopal Effect) Compared to Baseline

  End of study

Other Outcomes (1)

• Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Date treatment consent signed to date off study, approximately 14 months and 4 days.

Study Arms (1)

1/Avelumab 800 mg intravenous (IV) every two weeks in combination with radiation therapy

EXPERIMENTAL

Avelumab 800 mg IV every two weeks in combination with radiation therapy

Biological: Avelumab; Radiation: External beam radiotherapy

Interventions

Avelumab BIOLOGICAL

Avelumab 800 mg intravenous (IV) over 60 minutes (+/- 20 minutes) on days 1 and 15 of each 28-day cycle

Also known as: MSB0010718C

1/Avelumab 800 mg intravenous (IV) every two weeks in combination with radiation therapy

External beam radiotherapy RADIATION

5 gray (Gy) per fraction will be delivered on 5 consecutive treatment days for a total dose 25 Gy

1/Avelumab 800 mg intravenous (IV) every two weeks in combination with radiation therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a documented diagnosis of multiple myeloma defined by the International Myeloma Working Group Criteria (IMWG)(3). Patients at initial diagnosis must have had a serum M-protein greater than or equal to 3 g/dL and/or bone marrow plasma cells greater than or equal to 10%, and at least one of the following:
• Anemia: Hemoglobin less than or equal to10 g/dL, or
• Renal failure: serum creatinine greater than or equal to 2.0 mg/dL, or
• Hypercalcemia: Calcium (Ca) greater than or equal to10.5 mg/dL, or
• Lytic bone lesions on X-ray, computed tomography (CT), or positron emission tomography (PET)/CT, or
• greater than or equal to 2 focal lesions on spinal magnetic resonance imaging (MRI), or
• greater than or equal to 60% bone marrow plasma cells, or
• Involved/un-involved serum free light chain ratio greater than or equal to 100
• Have at least one extramedullary plasmacytoma or lytic lesion which at the discretion of the investigators is amenable to and clinically indicated for localized radiation therapy
• Must have Relapsed or Relapsed and Refractory Multiple Myeloma. Patients must have documented evidence of progressive disease (PD) as defined by the IMWG criteria on or after their last regimen and must have achieved a minimal response (MR) or better to at least one prior regimen. Definitions by the IMWG:
• Relapsed and refractory: disease that is nonresponsive while on salvage therapy or progresses within 60 days of last therapy in patients who have achieved minor response (MR) or better
• Relapsed: disease that progresses and requires the initiation of salvage therapy but does not meet criteria for either primary refractory or relapsed and refractory MM categories
• Patients must have been previously treated for MM and be refractory to, not a candidate for (ineligible), or intolerant of available therapeutic regimens known to provide clinical benefit including immunomodulatory (IMiD), proteasome inhibitor, and anti-cluster of differentiation (CD)38 monoclonal antibody-based treatments.
• Documented measurable disease within the 4 weeks prior to registration defined by any one of the following:
• Monoclonal Bone marrow plasma cells greater than or equal to 5%

You may not qualify if:

• Patients with clinically unstable lesions (e.g., impending cord compression) where a delay in receiving radiation therapy (XRT) would be detrimental are not eligible
• Current or prior anti-cancer treatment prior to the first dose of avelumab as defined below:
• Chemotherapy, targeted small molecule therapy, or other anti-cancer treatment not otherwise specified below within 2 weeks
• Radiation therapy within 2 weeks
• Anti-cancer monoclonal antibody (mAb) treatment within 4 weeks
• Use of an investigational agent (e.g., biologic, drug, or other) within 4 weeks
• Allogeneic stem cell transplant
• No autoimmune disease, as follows:
• Active (acute or chronic) autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with type I diabetes, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment may be eligible.
• History of serious autoimmune-related disorders including immune colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis whether drug- mediated or not.
• Current use of immunosuppressive medication, EXCEPT for the following:
• Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
• Systemic corticosteroids at physiologic doses
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Uncontrolled intercurrent illness including, but not limited to the following that may limit interpretation of results or that could increase risk to the patient in the judgment of the investigator:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Multiple Myeloma

Interventions

avelumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr. Mark Roschewski
• Organization: National Cancer Institute

mark.roschewski@nih.gov

240-760-6183

Study Officials

• Mark Roschewski, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 9, 2019
• First Posted: April 10, 2019
• Study Start: October 17, 2019
• Primary Completion: November 4, 2020
• Study Completion: November 4, 2020
• Last Updated: May 12, 2021
• Results First Posted: April 20, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)