Pembrolizumab as Salvage Therapy for the Treatment of Multiple Myeloma in Patients Progressing on CAR-T Cell Therapy

NCT05204160 | Withdrawn Phase 2 DMC FDA Drug

• 4 other identifiers: STUDY00003182NCI-2021-08718Winship5388-21P30CA138292
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effect of pembrolizumab in treating patients with multiple myeloma that is growing, spreading, or getting worse (progressing) on chimeric antigen receptor (CAR)-T cell therapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  The ORR is defined as the proportion of treated subjects who achieve a best response of minimal residual disease negativity, complete response (CR), stringent (s)CR, very good partial response, or partial response using the International Myeloma Working Group criteria. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Proportion of patients achieving stable disease or better will also be reported at 6 months and 12 months; Response rates will be reported along with 95% confidence intervals will be estimated using the Clopper-Pearson method. Chi-square test will be used to compare the efficacy in term of tumor response rate between the different groups.

  Up to 3 years

Secondary Outcomes (4)

• Progression-free survival (PFS)

  Up to 3 years

• Overall survival (OS)

  Up to 3 years

• Immunogenicity of the salvage regimen

  Up to 3 years

• Incidence of adverse events (AEs)

  Up to 3 years

Study Arms (1)

Treatment (pembrolizumab)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Biological: Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Subject is, in the investigator's opinion, willing and able to comply with the protocol requirements
• Subject has given voluntary signed written informed consent before performance of any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Have documented multiple myeloma as defined by the International Myeloma Working Group (IMWG) 2014 criteria including: Clonal bone marrow plasma cells \>= 10% (If bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement). In addition, the patient must meet one of the criteria in c1 or c2:
• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically (one or more of the following):
• Hypercalcemia: serum calcium \> 0.25 mmol/L (\> 1 mg/dL) higher than the upper limit of normal (ULN) or \> 2.75 mmol/L (\> 11 mg/dL)
• Renal insufficiency: Creatinine clearance (CrCl) \< 40 mL/min (measured or estimated by validated equations) or serum creatinine \> 177 umol/L (\> 2 mg/dL)
• Anemia: hemoglobin value of \> 20 g/L below the lower limit of normal, or a hemoglobin value \< 100 g/L
• Bone lesions: 1 or more osteolytic lesions on skeletal radiography, computed tomography (CT), or magnetic resonance imaging (MRI) (Clonality should be established by showing kappa/lambda-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used)
• Any one or more of the following:
• Clonal bone marrow plasma cell percentage \>= 60% (Clonality should be established by showing kappa/lambda-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used)
• Involved: uninvolved serum free light chain (FLC) ratio \> 100 (These values are based on the serum Freelite assay. The involved FLC must be \>= 100 mg/L
• \> 1 focal lesions on MRI studies; Each focal lesion must be 5 mm or more in size
• Measurable disease as defined by any of the following:
• Serum M-protein level \>= 1.0 g/dL or urine M-protein level \>= 200 mg/24 hours

You may not qualify if:

• Renal insufficiency, defined as creatinine clearance =\< 30 mL/min (either actual or calculated value), within 21 days of initiation of protocol therapy. The Cockcroft - Gault formula should be used for calculating creatinine clearance values
• Platelet count =\< 75,000 cells/mm\^3 at time of screening evaluation. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment
• Participants with an absolute neutrophil count (ANC) =\< 1000 cells/mm\^3 at time of screening evaluation. Growth factors may not be used to meet ANC eligibility criteria within 14 days of obtaining screening evaluation
• Participants with hemoglobin level \< 7.5 g/dL, at time of screening. Transfusion may not be used to meet eligibility criteria within 7 days of obtaining screening evaluation
• Participant had undergone ACT \> 12 weeks from study enrollment
• Participants with hepatic impairment, defined as bilirubin \>= 1.5 x institutional upper limit of normal (ULN) or aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]), or alkaline phosphatase \>= 3x institutional ULN
• Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but no more than 10 mg orally \[p.o.\] once daily \[q.d.\] or its equivalent) for other rheumatological manifestations. Doses of corticosteroid should be stable for at least 7 days prior to study treatment.)
• Known significant cardiac abnormalities including:
• Congestive heart failure, New York Heart Association (NYHA) class III or IV
• Uncontrolled angina, arrhythmia or hypertension
• Myocardial infarction within the past six months
• Any other uncontrolled or severe cardiovascular condition
• Prior cerebrovascular event with residual neurologic deficit
• Serious, intercurrent illness including, but not limited to, clinically relevant active infection, known active hepatitis B or C viral infection, known human immunodeficiency virus (HIV) infection, uncontrolled diabetes mellitus, or serious co-morbid medical conditions such as chronic restrictive pulmonary disease, and cirrhosis
• Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study

Sponsors & Collaborators

• Emory University: lead
• Merck Sharp & Dohme LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pembrolizumab

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

Study Officials

• Ajay K Nooka, MD,MPH,FACP

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: January 24, 2022
• Study Start: April 11, 2022
• Primary Completion: February 27, 2024
• Study Completion: February 27, 2024
• Last Updated: July 3, 2024

Record last verified: 2024-07

Locations

US (1)