| CTRI Number |
CTRI/2025/03/082608 [Registered on: 18/03/2025] Trial Registered Prospectively |
| Last Modified On: |
10/03/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Biological |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Study of immunotherapy in combination with CAR-T cell therapy in patients with relapsed or refractory DLBCL |
|
Scientific Title of Study
|
Phase II study of immunotherapy in combination with CAR T cell therapy ACTALY CEL in adults adolescents patients with relapsed refractory DLBCL |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Hasmukh Jain |
| Designation |
Professor |
| Affiliation |
Tata Memorial Hospital |
| Address |
Room No 81,
Adult Hematolymphoid Unit,
Medical Oncology Department,
Main Building Ground Floor,
Tata Memorial Hospital, Parel
Mumbai
MAHARASHTRA
400012
India |
| Phone |
0912224177000 |
| Fax |
|
| Email |
dr.hkjain@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Hasmukh Jain |
| Designation |
Professor |
| Affiliation |
Tata Memorial Hospital |
| Address |
Room No 81,
Adult Hematolymphoid Unit,
Medical Oncology Department,
Main Building Ground Floor,
Tata Memorial Hospital, Parel
Mumbai
MAHARASHTRA
400012
India |
| Phone |
0912224177000 |
| Fax |
|
| Email |
dr.hkjain@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Hasmukh Jain |
| Designation |
Professor |
| Affiliation |
Tata Memorial Hospital |
| Address |
Room No 81,
Adult Hematolymphoid Unit,
Medical Oncology Department,
Main Building Ground Floor,
Tata Memorial Hospital, Parel
Mumbai
MAHARASHTRA
400012
India |
| Phone |
0912224177000 |
| Fax |
|
| Email |
dr.hkjain@gmail.com |
|
|
Source of Monetary or Material Support
|
| Indian Council of Medical Research,
V. Ramalingaswami Bhawan, P.O. Box No. 4911
Ansari Nagar, New Delhi - 110029, India |
|
|
Primary Sponsor
|
| Name |
Dr Hasmukh Jain |
| Address |
Room No 81,
Adult Hematolymphoid Unit,
Medical Oncology Department,
Main Building Ground Floor,
Tata Memorial Hospital, Parel, Mumbai - 400012 |
| Type of Sponsor |
Other [Self] |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Hasmukh Jain |
Tata Memorial Hospital |
Room No 81,
Adult Hematolymphoid Unit,
Medical Oncology Department,
Main Building Ground Floor,
Tata Memorial Hospital, Parel, Mumbai - 400012
Mumbai
MAHARASHTRA |
0912224177000
dr.hkjain@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee-I |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C859||Non-Hodgkin lymphoma, unspecified, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
CAR-T cell therapy |
Actaly-cel, a CAR-T cell therapy will be the standard of care. This is a single infusion given on Day 0 |
| Intervention |
CAR-T cell therapy plus Nivolumab |
Nivolumab (40mg), an immunotherapy will be administered once in 28 days for 6 cycles after completion of CAR-T cell therapy Day 28 |
| Intervention |
CAR-T cell therapy plus Nivolumab plus reinfusion of CAR-T cell therapy |
After the initial CAR-T cell therapy infusion, a reinfusion will be administered within Day 28 to Day 90.
Dose: 10x10^6 CAR T cells/Kg (with 20% margin)
Following this, Nivolumab (40mg), an immunotherapy will be administered once in 28 days for 6 cycles after completion of the reinfusion Day 28 |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
80.00 Year(s) |
| Gender |
Both |
| Details |
1. Age more than equal to 18 years
2. Histologically confirmed diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, transformed follicular lymphoma and high-grade B-cell NHL.
3. Patient achieved Complete Response on day 28 response assessment post Actaly-cel infusion.
The complete inclusion criteria is available in the protocol
4. Indication for CART1 Actaly cel first dose should be chemotherapy refractory disease defined as progressive or stable disease as the best response to the most recent chemotherapy regimen or disease progression or relapse within 12 months after autologous stem cell transplantation ASCT
5. Subject must have received an anti CD20 monoclonal antibody and an anthracycline containing regimen Patients with transformed follicular lymphoma must have been treated for follicular lymphoma and have refractory disease after transformation
6. Subject must have received CART1 Actaly cel first dose at a target dose of 5x10 to the power of 6, CAR T cells per Kg with 20 percent margin
7. Patient is not willing or not feasible to undergo ASCT
8. Patient life expectancy 12 weeks or more
9. Eastern Cooperative Oncology Group performance status of 0 to 2 at the time of screening
10. Adequate organ function at the time of screening
a. Renal function a serum creatinine of 1.5 times upper limit of normal ULN or an estimated glomerular filtration rate 60 mL per min per 1.73 m2 or more
b. Liver function Alanine Aminotransferase 2.5 times the ULN for age and gender and bilirubin 2.0 mg per dl or less unless the patient had Gilbert syndrome in which case they can be included if their total bilirubin is 5.0 times ULN or less and direct bilirubin is 1.5 times ULN or less
c. A minimum level of pulmonary reserve defined as grade 1 or less dyspnea and pulse oxygenation more than 91 percent on room air
d. Hemodynamically stable and left ventricular ejection fraction 45 percent or more confirmed by echocardiogram or multiple gated acquisition scan No evidence of pericardial effusion
e. Adequate bone marrow reserve defined as absolute neutrophil count more than 1000 per mm3 platelets 50000 per mm3 or more and hemoglobin more than 8.0 g per dl
11. Sexually active patients women of childbearing potential are required to use highly effective methods of contraception for at least 12 months following CAR T cell infusion |
|
| ExclusionCriteria |
| Details |
1. Grade 3 or 4 CRS, ICANS, IEC-HS from previous treatment with specific anti-CD19 or anti-CD3 therapy or any other anti-CD19 directed therapy.
2. Need for mechanical ventilation or vasopressors during the previous treatment with Actaly-cel
3. Active central nervous system involvement by malignancy.
4. Active replication of prior infection with hepatitis B or active hepatitis C HCV RNA positive or HIV positive patients
5. Uncontrolled acute life-threatening bacterial viral or fungal infection i.e. blood culture positive 72 hours before infusion
6. Unstable angina and or myocardial infarction within 6 months before screening or cardiac arrhythmia not controlled with medical management
7. Previous or concurrent malignancies except in the case of adequately treated basal cell or squamous cell carcinoma in situ carcinoma of the cervix or breast treated curatively and without evidence of recurrence for 3 years before study or primary malignancy which has been completely resected and in complete remission for 5 years
8. Currently pregnant or lactating female subjects
9. Previous treatment with antibodies targeting immune checkpoint pathways such as anti PD 1 anti PD L1 anti CD137 or anti CTLA 4 or other agents that modulate T cell co-stimulation
10. Patients with active or known autoimmune diseases including immune colitis inflammatory bowel disease immune pneumonitis pulmonary fibrosis or psychiatric conditions including those within the past year will be excluded However patients with type 1 diabetes mellitus residual hypothyroidism due to autoimmune thyroiditis requiring only hormone replacement or skin conditions e.g. vitiligo psoriasis or alopecia not requiring systemic treatment may be included
11. A history of severe hypersensitivity to the investigational product or any component of its formulation including severe reactions to monoclonal antibodies NCI CTCAE v5 Grade 3 |
|
|
Method of Generating Random Sequence
|
Stratified randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Disease-free survival defined as the time from enrollment to disease recurrence, or death. |
At the end of 1-year |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Overall Survival (OS)
Acute and long-term toxicities
CAR RQ PCR monitoring
B and T-cell enumeration
|
1 year follow up |
|
|
Target Sample Size
|
Total Sample Size="100"
Sample Size from India="100"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
01/04/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Brief Summary:
Background or Rationale: Patients with DLBCL, a type of blood cancer, who do not respond to regular chemotherapy are treated with a new treatment called CAR-T cell therapy. In the CAR-T cells therapy patients own cells (T cells) are modified in the lab to fight against the cancer. This treatment works in about 40 percent of the patients. The efficiency of CAR-T cell therapy depends on how long the CAR-T cells can survive in the body. In this study we are exploring two strategies to improve the persistence of CAR-T cells, one is to give a drug called Nivolumab and another approach is to give a repeat CAR-T infusion about a month after the first CAR-T cell therapy followed by the use of nivolumab. We will study these two approaches against the standard practice of using CAR-T cell therapy alone. This study will ensure that every patient will at least receive the standard treatment.
Objective of the study: The primary objective is to compare the groups and determine how many patients survive and remain disease-free over the period of one year.
Protocol Schema: This is a randomized controlled trial and will include patients with relapsed or refractory DLBCL, who are more than or equal to 18 years of age. Patients who are treated at Tata Memorial Hospital will be screened and enrolled in the study. Each participant will have an equal chance of being randomly assigned to any one of the study arms. The study will span for a total duration of 3 years, with the first 2 years of enrollment and 1 year for follow-up.
Study Procedure:
Patients with relapsed or refractory DLBCL who are free from disease after receiving the first CAR-T cells therapy will be assessed by the study investigators and if eligible will be enrolled in the study, Routine investigations will be performed as per standard practice. Eligible patients will be enrolled and randomized into one of the three study arms on Day 28 after first CAR-T cell therapy.
The three arms of the study are described below,
Arm A - CAR-T cell therapy alone (Standard of Care) Arm B - CAR-T cell therapy plus Nivolumab
Arm C - CAR-T cell therapy plus CAR-T cell therapy re-infusion (CART2) plus Nivolumab.
Nivolumab will be administered through an IV line every 4 weeks for total of 6 cycles. In these patients some additional hormonal and lipid profile tests will be performed to monitor any side effects.
CAR-T cell therapy re-infusion will be performed by giving the remaining cells which were modified for the first CAR-T cell therapy infusion. Patients who receive re-infusion will be admitted and monitored for side effects according to the standard practice.
After 6 months, we will perform a PET-CT scan on all patients to determine whether the disease remains cured or if it has returned. This will be done if there is a clinical suspicion of disease recurrence and also after 12 months.
Analysis: We will mostly use descriptive methods to summarize the results. The Kaplan-Meier method will be used to measure how long patients survive without the disease coming back. |