Georgia's Online Cancer Information Center

Find A Clinical Trial

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

Status
Active
Cancer Type
Multiple Myeloma
Plasma cell neoplasm
Trial Phase
Phase II
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCT ID
NCT05204160
Protocol IDs
Winship5388-21 (primary)
NCI-2021-08718
STUDY00003182
Study Sponsor
Emory University Hospital/Winship Cancer Institute

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.

Objectives

PRIMARY OBJECTIVES:
I. To evaluate the efficacy of pembrolizumab in patients who have received B- cell maturation antigen (BCMA)-directed adoptive cell therapy (ACT) and have clinical evidence of progression.
II. To obtain anti-tumor activity (best response rates: objective response rate [ORR], very good partial response, [VGPR], complete response [CR], stringent complete remission [sCR], minimal response disease [MRD] negativity) in patients treated with pembrolizumab.

SECONDARY OBJECTIVES:
I. To evaluate the expansion of engrafted T cells following pembrolizumab administration in the peripheral blood and within the tumor microenvironment.
II. To evaluate the phenotype and function of engrafted T cells following pembrolizumab administration.
III. Progression free survival (PFS) and overall survival (OS) among patients progressing after ACT that received pembrolizumab.
IV. To determine immunogenicity of the salvage regimen.

OUTLINE:
Patients receive pembrolizumab intravenously (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.

After completion of study treatment, patients are followed up every 3 months.

Eligibility

  1. Subject is, in the investigator’s opinion, willing and able to comply with the protocol requirements
  2. 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of any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care
  3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
  4. 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
  5. 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 * IgA, IgD, IgE, or IgM multiple myeloma: serum M-protein level >= 0.5 g/dL or urine M-protein level >= 200 mg/24 hours; or * Light chain multiple myeloma without measurable disease in the urine: serum Ig free light chain (FLC) >= 10 mg/dL and abnormal serum Ig kappa/lambda FLC ratio
  6. Must have undergone BCMA-directed CART cell therapy and have evidence of progression per IMWG criteria upon response assessment
  7. Must be refractory to or intolerant of all established therapies known to provide clinical benefit in MM and who have received a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 antibody (mAb)
  8. Must have at least 4-week washout period for all the investigational monoclonal antibodies
  9. Must have resolution of toxicities from prior therapies to less than or equal to grade 1 (Grade =< 1)
  10. Men and women, age >= 18 years or legal age of consent per local regulations (whichever is greater)
  11. Female patients who: * Are postmenopausal for at least 1 year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) * Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 – 14 days prior to and again within 24 hours of starting study drugs
  12. Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following: * Agree to practice effective barrier contraception during the entire study treatment period and through 4 weeks after the last dose of study drug, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.
Georgia CORE

 

Advancing Cancer Care through Partnerships and Innovation

Georgia CORE is a statewide nonprofit that leverages partnerships and innovation to attract more clinical trials, increase research, and promote education and early detection to improve cancer care for Georgians in rural, urban, and suburban communities across the state.