NCT03910439

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

Terminated Phase 2 Results posted Last updated 12 May 2021

What this trial tests

Phase 2 trial testing Avelumab in Myeloma, Multiple in 4 participants. Terminated before completion.

Timeline

17 October 2019

Primary endpoint
4 November 2020

4 November 2020

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	4
Start date	17 October 2019
Primary completion	4 November 2020
Estimated completion	4 November 2020
Sites	1 location across United States

Drugs / interventions tested

• Avelumab (avelumab) — full drug profile →
• External beam radiotherapy

Conditions studied

• Myeloma, Multiple — all drugs for Myeloma, Multiple →
• Myeloma-Multiple — all drugs for Myeloma-Multiple →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Myeloma, Multiple or Myeloma-Multiple. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate (ORR) Primary · up to end of study, an average of 11 months

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-his

Complete Response

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	0	0 – 0

Stringent Complete Response

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	0	0 – 0

Partial Response

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	0	0 – 0

Very Good Partial Response

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	0	0 – 0

Fraction of Participants Who Experience a Complete Response (CR) or Stringent Complete Response (sCR) Using the Study Treatment Secondary · up to end of study for individual patient, an average of 11 months

Response was assessed by the International Myeloma Working Group (IMWG) response criteria, 2016. 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.

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	0	0 – 0

Fraction of Participants Who Experience a Minimal Residual Disease Negative (MRDneg)Complete Response (CR) Using the Study Treatment Secondary · up to up to end of study for individual patient, an average of 11 months

Response was assessed by the International Myeloma Working Group Criteria (IMWG) 2016 criteria. Sustained MRDnegCR is defined as negativity in the marrow (next-generation flow (NGF) or next-generation sequencing (NGS), or both) and by imaging confirmed minimum of 1 year apart.

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	0	0 – 0

Percent Change in Aberrant Circulating Plasma Cells in the Peripheral Blood (PB) and Bone Marrow (BM) From Baseline Secondary · Baseline and up to end of study for individual patient, an average of 11 months

Blood samples and bone marrow samples were taken from participants and processed by flow cytometry.

Peripheral blood at baseline

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	0	0 – 0

Bone marrow at baseline

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	0	0 – 0

Peripheral blood at end of study

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	18	-1 – 1000

Bone marrow at end of study

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	55	-0.01 – 1250

Progression-free Survival (PFS) Secondary · End of study, an average of 11 months

PFS was defined as those who progress or die without progression as failures, and censoring those who do not. Progressive disease was assessed by the 2016 International Myeloma Working Group (IMWG) response criteria and is an increase of 25% from lowest confirmed response value in one or more of the following criteria: Serum M-protein (absolute increase must be ≥0·5 g/dL); Serum M-protein increase ≥1 g/dL, if the lowest M component was ≥5 g/dL; Urine M-protein (absolute increase must be ≥200 mg/24 h); In patients without measurable serum and urine M-protein levels, the difference between invol

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	5.3	2.5 – 7.1

Percentage of Participants With Overall Survival (OS) Secondary · Enrollment through end of study, an average of 11 months

Participants who are alive following enrollment and study treatment.

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	100

Number of Participants With Grade ≥1 Non-serious Adverse Events Secondary · Date treatment consent signed to date off study, approximately 14 months and 4 days.

Grade ≥1 non-serious adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. Grade 1 is mild, Grade 2 is moderate, and Grade 3 is severe or medically significant.

Alanine aminotransferase increased

Group	Value	95% CI
Grade 1	1
Grade 2	1
Grade 3	0

Alkaline aminotransferase increased

Group	Value	95% CI
Grade 1	1
Grade 2	0
Grade 3	0

Arthralgia

Group	Value	95% CI
Grade 1	1
Grade 2	0
Grade 3	0

Aspartate aminotransferase increased

Group	Value	95% CI
Grade 1	1
Grade 2	1
Grade 3	0

Chest pain - cardiac

Group	Value	95% CI
Grade 1	0
Grade 2	1
Grade 3	0

Eye disorders - Other, posterior vitreous detachment

Group	Value	95% CI
Grade 1	1
Grade 2	0
Grade 3	0

Nausea

Group	Value	95% CI
Grade 1	1
Grade 2	0
Grade 3	0

Pain

Group	Value	95% CI
Grade 1	1
Grade 2	1
Grade 3	0

Number of Participants Overall Best Response Secondary · 4 weeks

Response was assessed by the International Myeloma Working Group (IMWG) response criteria, 2016. Minimal Response is ≥25% but ≤49% reduction of serum M-protein and reduction in 24-h urine M-protein by 50-89%; in addition, if present at baseline, a ≥50% reduction in the size (SPD) of soft tissue plasmacytomas is also required. Stable Disease is not meeting criteria for complete response, very good partial response, partial response, minimal response, or progressive disease. And Progressive Disease is appearance of a new lesion(s), ≥50% increase from nadir in sum of the products of diameters (SP

Minimal Response

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	1

Stable Disease

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	2

Progressive Disease

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	1

Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) Secondary · Date treatment consent signed to date off study, approximately 14 months and 4 days.

Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence.

Group	Value	95% CI
1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy	4

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 14 months and 4 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

1/Avelumab 800 mg Intravenous (IV) Every Two Weeks in Combination With Radiation Therapy

Serious: 0/4 (0%)

Deaths: 0/4

Other adverse events (12 terms — click to expand)

Reaction	System	1/Avelumab 800 mg Intraven…
Alanine aminotransferase increased	Investigations	—
Alkaline phosphatase increased	Investigations	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Aspartate aminotransferase increased	Investigations	—
Chest pain - cardiac	Musculoskeletal and connective tissue disorders	—
Eye disorders - Other, posterior vitreous detachment	Eye disorders	—
Nausea	Gastrointestinal disorders	—
Pain	General disorders	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—
Skin infection	Infections and infestations	—
Syncope	Nervous system disorders	—
Vomiting	Gastrointestinal disorders	—

Data from ClinicalTrials.gov NCT03910439 adverse events section.

Sponsor's own description

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....

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Avelumab, a PD-L1 Inhibitor, in Combination with Hypofractionated Radiotherapy and the Abscopal Effect in Relapsed Refractory Multiple Myeloma.
   Kazandjian D, Dew A, Hill E, Ramirez EG, et al · · 2021 · cited 16× · PMID 33554406 · DOI 10.1002/onco.13712