Health Condition 1: C90- Multiple myeloma and malignant plasma cell neoplasms
Conditions
Interventions
Intervention1: DRL-1801: Anti-BCMA CAR-T therapy. Duration of the intervention is one day.
Control Intervention1: Not Applicable: NA
Sponsors
Aurigene Oncology Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Males and females >= 18 years of age; 2. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1 (See Appendix D). (Note: Patients with ECOG PS of 2 because of Multiple Myeloma and not because of comorbidities can be enrolled). 3. Acceptable bone marrow and organ function at screening as described below: a. ANC >= 1000/μL (without WBC growth factor support) b. Platelet count >= 75,000/μL without transfusion support c. Hemoglobin >= 9 g/dL (Transfusion is allowed to achieve this Hb) d. Total Bilirubin e. AST (SGOT) f. ALT (SGPT) g. Creatinine Clearance (by Cockcroft Gault formula) ï?³ 30 ml/min 4. Documented diagnosis of multiple myeloma 5. Must have received prior treatment for Multiple Myeloma. Note: Both patients with or without hematopoietic stem cell transplant eligibility are allowed. 6. Patients must have measurable disease as per IMWG criteria (Kumar S et al, 2016), including at least one of the criteria below: • Serum M-protein greater or equal to 0.5 g/dL • Urine M-protein greater or equal to 200 mg/24 h • 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 7. Willing and able to provide written informed consent 8. Ability to communicate well with the investigator and to comply with the requirements of the entire study
Exclusion criteria
Exclusion criteria: 1.History or presence of clinically relevant central nervous system. 2.Patients with active or history of plasma cell leukemia, Waldenstromâ??s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly,endocrinopa thy, monoclonal protein, and skin changes),or clinically significant amyloidosis. 3.Patients with solitary plasmacytomas or non-secretory myeloma without other evidence of measurable disease. 4.Anti-cancer therapy, such as chemotherapy, immuno modulatory drug therapy, immunosuppressive therapy including corticosteroids (unless administered to prevent contrast material reactions during radiographic procedures) received within the past 14 days of LD therapy. Low dose chronic use of corticosteroids (equal to and less than 10 mg prednisone per day or equivalent) is allowed. 5.International ratio (INR) or partial thromboplas tin time (PTT) Greater than1.5x approximately equal to ULN, or history of Grade Greater than2 hemorrhage within 30 days, or patient requires ongoing treatment with chronic, therapeutic dosing of anti-coagulants (e.g., warfarin, low molecular weight heparin, or Factor Xa inhibitors). 6.Echocardiogram or MUGA scan with left ventricular ejection fraction Greater than 45 percentage. 7.Presence of an acute or chronic toxicity resulting from prior chemotherapy, with the exception of alopecia, that has not resolved to Grade equal to and less than 1, as determined by NCI CTCAE v 5.0. 8.Use of any investigational agent within 28 days or 5 half-lives (whichever is longer) prior to cycle 1 Day 1. 9.Previously exposed to any approved or investigational CAR-T therapy. 10.Current or previously treated myeloma in the CNS (Central Nervous System) including current or previous myeloma meningitis. 11.Major surgery Greater than 28 days from the start of treatment(major surgery is defined as a procedure requiring general anesthesia). 12.Minor surgery Greater than 14 days from the start of treatment (insertion of a vascular access device is not considered either major or minor surgery). 13.Active autoimmune disease or any medical condi tion requiring the use of systemic immunosuppressi ive medications (Greater than 10 mg/day of prednisone or equivalent). Patients with thyroid dysfunction,on thyr oid replacement therapy are allowed. Intermittent topical,inhaled or intranasal corticosteroids are allowed. 14.Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy. 15.Patient with known hypersensitivity to any component of DRL-1801, cyclophosphamide,fludarbine or tocilizumab. 16.Active infection requiring systemic therapy. Note: Prophylactic use of antibiotics is allowed. Any infection detected during screening period whi ch is resolved adequately according to investigator by Day 0 is allowed. 17.Receipt of any vaccines against infectious diseases (e.g., influenza) within 28 days of study drug administration. 18.Positive for Human immunodeficiency virus (HIV) positive or Hepatitis B or Hepatitis C during screening.14.Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy. 19.Relapse within 6 months of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| â?¢Percentage of patients who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple MyelomaTimepoint: 6 months and 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of patients who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple MyelomaTimepoint: 6 months & 24 months;Time from DRL-1801 infusion to first documentation of response of PR or betterTimepoint: 6 months & 24 months;Time from first documentation of response or PR or better to first documentation of disease progression or death from any cause, whichever occurs firstTimepoint: 6 months & 24 months;Time from DRL-1801 infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs firstTimepoint: 6 months & 24 months;Time from DRL-1801 infusion to time of death due to any causeTimepoint: 6 months & 24 months;Maximum transgene level (Cmax), Time to peak transgene level (Tmax), Area under the curve of the transgene level (AUC), including maximum expansion & duration of persistence of DRL-1801 cellsTimepoint: 6 months & 24 months;Type, frequency, & severity of adverse events (AEs), adverse events of special interest (AESI), serious adverse events (SAEs), cytokine release syndrome, neurotoxicity, infection & laboratory abnormalitiesTimepoint: 6 months & 24 months;Evaluate patients for MRD statusTimepoint: 6 months & 24 months;Change in patient-reported outcomes as measured by EORTC-QLQ-C30 and EORTC-QLQ-MY20 Timepoint: 6 months & 24 months | — |
Countries
India
Contacts
Public ContactDr Akhil Kumar
Aurigene Oncology limited (Subsidiary of Dr. Reddyâ??s Laboratories Limited).
Outcome results
None listed