Clinical trial NCT04677452: Dose Exploration Study OF JWCAR129, BCMA-Targeted CART for RRMM
Official title: An Open-Label Phase 1 Dose Exploration Study of JWCAR129, BCMA-targeted Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Safety and Efficacy
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2020-12-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, Phase 1 dose exploration study to evaluate the safety and tolerability and to determine recommended Phase 2 dose(s) of JWCAR129, a CAR T-cell product that targets B-cell maturation antigen (BCMA), in adult subjects with relapsed and/or refractory multiple myeloma.


Eligibility criteria: Inclusion Criteria:

1. 18 years old and above.
2. Signed the Informed Consent Form.
3. Diagnosis of multiple myeloma (MM) with relapsed and/or refractory disease. Subjects must have received at least 3 prior anti-myeloma treatment regimens (note: induction with or without bone marrow transplant and with or without maintenance therapy is considered one regimen). Subjects must be refractory to the last anti-myeloma treatment regimen prior to entering the study.

   1. Autologous hematopoietic stem cell transplantation.
   2. A regimen that included an immunomodulatory agent (eg, thalidomide, lenalidomide, pomalidomide) and a proteasome inhibitor (eg, bortezomib, carfilzomib, ixazomib), either alone or in combination. Subjects must have undergone at least 2 consecutive cycles of treatment for each regimen unless progressive disease was the best response to the regimen.
   3. Anti-CD38 (eg, daratumumab) as part of a combination regimen or as a monotherapy.

   Subjects who were not candidates to receive one or more of the above treatments (ie, contraindicated) are eligible; the reason for not receiving treatment must be clearly documented in the case report form.
4. Subjects must have measurable disease.
5. Subject must be willing to provide fresh bone marrow biopsy samples during Screening (and prior to study treatment, if required).
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
7. Adequate renal, bone marrow, hepatic, pulmonary, and cardiac function

Exclusion Criteria:

1. Subjects with known active or history of CNS involvement by malignancy
2. Subjects with solitary plasmacytoma; active or history of plasma cell leukemia (PCL); Waldenstrom's macroglobulinemia; Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasmaproliferative disorder, Skin changes (POEMS) syndrome; or symptomatic amyloidosis
3. History of another primary malignancy that has not been in remission for at least 3 years. The following are exempt from the 3-year limit: non-melanoma skin cancer, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, and in situ breast cancer that has been completely resected.
4. Require systemic immunosuppressive therapies (eg, calcineurin inhibitors, methotrexate, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-IL-6 or anti-IL-6 receptor \[IL-6R\])
5. Prior CAR T-cell or other genetically-modified T-cell therapy
6. Prior treatment with a BCMA-targeted agent
7. History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
8. Untreated or active infection at time of initial screening, at the time of leukapheresis, within 72 hrs before lymphodepletion, or 5 days before JWCAR129 infusion.
9. History of any of the following cardiovascular conditions within 6 months of initial screening: Class III or IV heart failure as defined by the New York Heart Association (NYHA), myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmias, or other clinically significant cardiac disease
10. History of severe immediate hypersensitivity reaction to any of the protocol-mandated or recommended agents used in this study
11. Allogeneic hematopoietic stem cell transplantation.

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: 28 days
measure: Incidence and severity of adverse events
timeFrame: 2 years
measure: Incidence and severity of clinically significant laboratory abnormalities
timeFrame: 2 years
Secondary outcomes:
measure: Cmax
timeFrame: 2 years
measure: Tmax
timeFrame: 2 years
measure: AUC
timeFrame: 2 years
measure: Duration of persistence
timeFrame: 2 years
measure: Overall response rate
timeFrame: 2 years
measure: CR rate
timeFrame: 2 years
Other outcomes:
Locations:
city: Suzhou
country: China
facility: First Affiliated Hospital, Soochow University
state: Jiangsu
Study officials:
References: