CTRI/2023/11/059795 [Registered on: 14/11/2023] Trial Registered Prospectively
Last Modified On:
14/03/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Other (Specify) [Cell Therapy]
Study Design
Other
Public Title of Study
Evaluation of the safety and efficacy of anti-BCMA CAR-T product (cell therapy) in Patients with Multiple Myeloma.
Scientific Title of Study
A Phase 1/2, Open Label, Multicenter Study to Evaluate the Efficacy and Safety of DRL-1801 in Patients with Relapsed and Refractory Multiple Myeloma (SWASTH).
Trial Acronym
SWASTH
Secondary IDs if Any
Secondary ID
Identifier
DRL-1801-201 Version 3.0 dated 19 Jun 2023.
Other
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Akhil Kumar
Designation
VP and Head, Clinical Development
Affiliation
Aurigene Oncology limited (Subsidiary of Dr. Reddy’s Laboratories Limited).
Address
A39-40, KIADB Industrial Area, Phase II, Electronic City Hosur Road (Subsidiary of Dr. Reddys Laboratories limited) Bangalore
KARNATAKA
560100
India.
Bangalore KARNATAKA 560100 India
Phone
9632203510
Fax
Email
akhil_k@aurigene.com
Details of Contact Person Scientific Query
Name
Dr Divyesh Mandavia
Designation
Associate Director and Medical Lead, Clinical Development
Affiliation
Aurigene Oncology limited (Subsidiary of Dr. Reddy’s Laboratories Limited).
Address
A39-40, KIADB Industrial Area, Phase II, Electronic City Hosur Road (Subsidiary of Dr. Reddys Laboratories limited) Bangalore
KARNATAKA
560100
India.
Bangalore KARNATAKA 560100 India
Phone
9427181182
Fax
Email
divyesh_m@aurigene.com
Details of Contact Person Public Query
Name
Mukesh Kumar Ramashre Saroj
Designation
Assistant Clinical Project Manager
Affiliation
Aurigene Oncology limited (Subsidiary of Dr. Reddy’s Laboratories Limited).
Address
A39-40, KIADB Industrial Area, Phase II, Electronic City Hosur Road (Subsidiary of Dr. Reddys Laboratories limited) Bangalore
KARNATAKA
560100
India.
Bangalore KARNATAKA 560100 India
Phone
9769090249
Fax
Email
mukesh_s@aurigene.com
Source of Monetary or Material Support
Aurigene Oncology Limited, 39-40, KIADB Industrial Area Phase II Electronic City Hosur Road Bangalore 560 100 Karnataka India.
Primary Sponsor
Name
Aurigene Oncology Limited
Address
39-40, KIADB Industrial Area Phase II Electronic City Hosur Road Bangalore 560 100 Karnataka India.
JAWAHARLAL INSTITUTE OF POSTGRADUTE MEDICAL EDUCATION AND RESEARCH
3rd floor, Department of Medical oncology, Super speciality Block, JIPMER campus road, Gorimedu,Dhanavantri Nagar, Puducherry-605006 Pondicherry PONDICHERRY
8056338405
drbiswajitdm@gmail.com
Dr Hari Menon
St. Johns Medical College and Hospital
Department of medical oncology, 2nd floor office area, oncology block, Koramangala, Bangalore, Karnataka -560034 Bangalore KARNATAKA
9819913164
hari.menon@stjohns.in
Dr Manju Sengar
Tata memorial Hospital
81,OPD, Adult hemotolymphiod OPD, Main Building, Ground Floor,Tata memorial Hospital Parel, Mumbai, Maharashtra 400012
Mumbai MAHARASHTRA
Institutional Ethics Committee-Clinical Studies, Apollo Hospitals Enterprise Limited
Approved
Institutional review board and Ethics committee, Christian Medical College and Hospital
Approved
TMH, Institutional Ethics Committee-I ,Tata Memorial Hospital
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C90||Multiple myeloma and malignant plasma cell neoplasms,
Intervention / Comparator Agent
Type
Name
Details
Intervention
DRL-1801
Anti-BCMA CAR-T therapy. Duration of the intervention is one day.
Comparator Agent
Not Applicable
NA
Inclusion Criteria
Age From
18.00 Year(s)
Age To
60.00 Year(s)
Gender
Both
Details
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 ≤ 1.5 x ULN; (Patients with known Gilbert’s syndrome are allowed with a Total Bilirubin ≤ 2.5 x ULN)
e. AST (SGOT) ≤ 3 x ULN (≤ 5 × ULN if known myeloma in the liver)
f. ALT (SGPT) ≤ 3 x ULN (≤ 5 × ULN if known myeloma in the liver)
g. Creatinine Clearance (by Cockcroft Gault formula) 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
ExclusionCriteria
Details
1.History or presence of clinically relevant central nervous system.
2.Patients with active or history of plasma cell leukemia, Waldenstrom’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 an autologous trans plant.
20.Uncontrolled congestive heart failure (New York Heart Association [NYHA] Class 2-4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, or transient ischemic attack, or pulmonary embolis m within 3 months prior to enrolment visit(Day 0).
21.Ongoing cardiac dysrhythmias requiring treatme nt of any grade or treatment of cardiac drsrhythia s in past 3 months, before enrolment visit (Day 0).
22.Uncontrolled intercurrent illness.
23.Current swab-positive or suspected (under investigation) Covid-19 infection or fever and other signs or symptoms suggestive of Covid-19 infection with recent contact of person(s) with confirmed Covid-19 infection, at screening or Day 0.
24.History of another primary malignancy within 5 years prior to starting study drug, except for ade quately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study.
25.Positive pregnancy test for women of child-bea ring potential (WOCBP) at the screening or enrolme nt visit (Day 0).
26.Lactating women or WOCBP who are neither surgi cally sterilized nor willing to use reliable contr aceptive methods (hormonal contraceptive, IUD, or any double combination of male or female condom, spermicidal gel, diaphragm, sponge, cervical cap).
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
• Percentage of patients who achieved
partial response (PR) or better
according to IMWG Uniform
Response Criteria for Multiple
Myeloma
6 months and 24 months
Secondary Outcome
Outcome
TimePoints
Percentage of patients who achieved
partial response (PR) or better
according to IMWG Uniform
Response Criteria for Multiple
Myeloma
6 months & 24 months
Time from DRL-1801 infusion to first documentation of
response of PR or better
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 first
6 months & 24 months
Time from DRL-1801 infusion to first
documentation of progressive disease
(PD), or death due to any cause,
whichever occurs first
6 months & 24 months
Time from DRL-1801 infusion to time
of death due to any cause
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 cells
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 abnormalities
6 months & 24 months
Evaluate patients for MRD status
6 months & 24 months
Change in patient-reported outcomes as measured by EORTC-QLQ-C30
and EORTC-QLQ-MY20
6 months & 24 months
Target Sample Size
Total Sample Size="24" Sample Size from India="24" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase I /
II, an Interventional clinical trial of DRL-1801 (Investigational Product) in
Patients with Relapsed and Refractory Multiple Myeloma. DRL-1801 is a Chimeric
antigen receptor (CAR) T-cell therapy where T-cell are modified to express
anti-BCMA antibodies.The study will be
conducted in many centres across India. This study is Single dose
administration of DRL-1801. Patients will be followed in the study for a
minimum of 24 months after DRL-1801 infusion and the study will consist of 3
periods i.e. pre-treatment period, treatment period and post-treatment period.
The pre-treatment
period of the study will consist of screening for eligibility, leukapheresis
and baseline evaluations (prior to lymphodepleting chemotherapy).
The treatment period
will start with initiation and completion of three days of lymphodepleting
chemotherapy (Day -5 though Day -3), followed by DRL-1801 infusion on Day 0.
So, treatment period is of 6 days from Day (-5) to Day 0 till DRL-1801
infusion.
The post-treatment
period will start from after the DRL-1801 administration and will consist of
efficacy and safety follow-up visits. These will include monthly evaluations
until month 24 post-DRL-1801 infusion or until disease progression, whichever
is longer.
Upon discontinuation
from this study, all patients who received DRL-1801 will participate in a
long-term follow-up and will be monitored for delayed toxicities related to
DRL-1801 and viral vector safety. Patients will be monitored for up to 5 years
from the date of their last DRL-1801 infusion.