Health Condition 1: C900- Multiple myeloma
Conditions
Interventions
Intervention1: hBCMA CAR-T cell: The investigational drug product is hBCMA is BCMA targeted Chimeric Antigen
Receptor (CAR) T cells for cancer treatment. It is a cell and gene therapy product.
hBCMA
Sponsors
Immunoadoptive Cell Therapy Private Limited (ImmunoACT)
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age - 18 years and above 2. ECOG 0-2 3. Subjects with diagnosis of multiple myeloma who have received at least two lines of therapy or double refractory to immunomodulatory drug (IMiD) and proteasome inhibitor (PI) combination or refractory to last line of treatment. 4. Measurable Disease defined by at least one of the criteria a. Serum M-protein greater or equal to 1.0 g/dL b. Urine M-protein greater or equal to 200 mg/24 h c. Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal d. A biopsy-proven evaluable plasmacytoma e. Bone marrow plasma cells >= 10% of total bone marrow cells 5. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study. 6. Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy. 7. Ability and willingness to adhere to the study visit schedule and all protocol requirements. 8. Written informed consent.
Exclusion criteria
Exclusion criteria: 1 Subjects who received the following treatments will be excluded a. Any therapy that is targeted to B-cell maturation antigen (BCMA) b. Ongoing treatment with chronic immunosuppressants since 2 weeks (eg cyclosporine or systemic steroids at any dose) c. Previous history of an allogeneic bone marrow transplantation or treatment with any gene therapy-based therapeutic for cancer Any prior systemic therapy for MM within 14 days prior to scheduled protocol required leukapheresis 2. LVEF less than 50 percent 3. Subjects with a history of class III or IV congestive heart failure (CHF) or severe non ischemic cardiomyopathy, history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months 4. Subjects with known active, or prior history of central nervous system (CNS) involvement 5. Subjects with plasma cell leukaemia 6. Subjects with solitary plasmacytomas without other evidence of measurable disease 7. Subjects with second malignancies in addition to myeloma if the second malignancy has required therapy in the last 3 years or is not in complete remission; exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or incidental histologic finding of prostate cancer (T1a or T1b using the TNM tumour, nodes, metastasis clinical staging system) or prostate cancer that is curative 8. Inadequate hepatic function defined by AST and ALT greater than 5 times the upper limit of normal (ULN) and direct bilirubin greater than 2 times ULN 9. Inadequate renal function defined by CrCl less than or equal to 30 ml/min using Cockcroft-Gault equation 10. International ratio (INR) or partial thromboplastin time (PTT) greater than three times ULN, unless on a stable dose of anticoagulant for a thromboembolic event, or history of grade 2 or more hemorrhage within 30 days 11. Evidence of human immunodeficiency virus (HIV) infection 12. Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV) 13. Seropositive for and with active viral infection with hepatitis C virus (HCV) 14. Pregnant or lactating women 15. Significant comorbidities or disease which in the judgement of the Investigator would place the subject at undue risk or interfere with the study 16. Vaccinated with live, attenuated vaccine within 4 weeks prior to apheresis 17. History of cerebrovascular accident or seizures in last 6 months 18. Patient with history of auto-immune disorders to be excluded
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I Safety The MTD is the highest dose that causes DLTs in greater than or equal to 2 of 6 subjects. For a dose level to be declared the MTD at least 5 evaluable subject must be enrolled with no DLTs reported or 6 evaluable subjects if 1 subject experiences a DLT. Phase II Overall Response Rate Percentage of subjects who achieved a PR or better according to IMWG Uniform Response Criteria for Multiple Myeloma.Timepoint: Phase I Safety DLT will be assessed within 21 days post administration of hBCMA CAR Phase II Overall Response Rate: 3 Months | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase I hBCMA persistence and quantificationTimepoint: Day -1, Day7, Day14, Day 21, Day28, month 3, month 6, month 9, month 12. This will be done only till two sequential tests are negative.;Phase I & II: Overall SurvivalTimepoint: 5 years : (Time from the first infusion to time of death due to any cause);Phase I & II: Progression Free SurvivalTimepoint: 5 years (Time from the first infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first) ;Phase I: Overall Response RateTimepoint: Month 3;Phase I & II: Duration of ResponseTimepoint: 5 year Follow up period:(Time from first documentation of response of PR or better to first documentation of response to disease progression or death from any cause, whichever occurs first) | — |
Countries
India
Contacts
Public ContactDr Manju Sengar
Tata Memorial Centre
Outcome results
None listed