Trial Title:
Study of IMPT-314 in R/R Aggressive B-cell NHL
NCT ID:
NCT05826535
Condition:
Relapsed Non-Hodgkin Lymphoma
Refractory Non-Hodgkin Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Conditions: Keywords:
CAR T-cell
Non-Hodgkin Lymphoma
CD19/20
CD19
CD20
NHL
Diffuse Large B-cell lymphoma
DLBCL
Transformed follicular lymphoma
TFL
Primary mediastinal B-cell lymphoma
PMBCL
High-grade B-cell lymphoma
HGBL
follicular lymphoma Grade 3B
large cell follicular lymphoma
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Dose finding Phase I followed by a Phase II part. Two Phase I dose levels and one Phase
II dose level. Three cohorts in each phase.
Primary purpose:
Treatment
Masking:
Single (Outcomes Assessor)
Masking description:
Analysis of response will be performed by Blinded Independent Central Review (BICR)
Discordance between the Investigator assessment and BICR assessment will be evaluated for
each efficacy endpoints based on tumor assessments if BICR assessments are performed.
Intervention:
Intervention type:
Drug
Intervention name:
IMPT-314
Description:
CAR T-cell therapy
Arm group label:
Phase I Dose Level I CAR T experienced cohort
Arm group label:
Phase I Dose Level I CAR T naïve cohort
Arm group label:
Phase I Dose Level I Refractory disease or relapse within one year of first line therapy
Arm group label:
Phase I Dose Level II CAR T experienced cohort
Arm group label:
Phase I Dose Level II CAR T naïve cohort
Arm group label:
Phase I Dose Level II Refractory disease or relapse within one year of first line therapy
Arm group label:
Phase II CAR T experienced cohort
Arm group label:
Phase II CAR T naïve cohort
Arm group label:
Phase II Refractory disease or relapse within one year of first line therapy
Summary:
This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of
IMPT-314, a bispecific chimeric antigen receptor (CAR) targeting cluster of
differentiation (CD)19 and CD20 in participants with aggressive B-cell NHL. Three cohorts
of participants will be enrolled: 1) CAR T naïve after at least two or more prior lines
of treatment, 2) CAR T experienced and 3) refractory disease or relapse within one year
of first line therapy.
Up to approximately 90 patients (30 per cohort) will be enrolled in dose finding Phase 1
part of the study, which will determine the recommended phase 2 dose.
Phase 2 will enroll up to approximately 60 additional participants (20 per cohort) to
evaluate further the safety and efficacy of IMPT-314.
IMPT-314 treatment consists of a single infusion of CAR-transduced autologous T cells
administered intravenously after a conditioning chemotherapy regimen consisting of
fludarabine and cyclophosphamide, administered over 3 days.
Individual participants will remain in the active post-treatment period for approximately
2 years. Participants will continue in long-term follow-up for 15 years from treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age 18 years or older
2. Willing and able to provide written informed consent
3. Histologically confirmed aggressive NHL, including the following types defined by
the World Health Organization (WHO 2017):
- DLBCL
- DLBCL arising from follicular lymphoma (Transformed FL)
- Primary mediastinal (thymic) large B-cell lymphoma
- High-grade large B-cell lymphoma with or without MYC and BCL2 and/or BCL6
rearrangement
- Grade 3b follicular lymphoma/Large cell follicular lymphoma
4. Received at least 1 prior line of therapy. Prior therapy must have included:
- Anti-CD20 monoclonal antibody
- An anthracycline containing chemotherapy regimen
- Participants with TFL must have received at least one of their prior lines of
therapy after transformation to DLBCL
5. Relapsed or refractory disease, defined by the following:
- Disease progression after last regimen (including salvage therapy after
autologous stem cell transplantation [ASCT]). In participants who have only
received front-line therapy, progression should be ≤12 months of first-line
therapy.
- In patients who received two or more lines of therapy, refractory disease is
defined as failure to achieve a CR to last line of therapy (including CAR T
and/or salvage therapy).
- In patients who received one line of therapy, refractory disease is defined as
failure to achieve at least a PR after at least 4 cycles of therapy
6. At least 1 measurable lesion (the Lugano classification). Lesions that have been
previously irradiated will be considered measurable only if progression has been
documented following completion of radiation therapy
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Absolute neutrophil count (ANC) ≥ 1000/uL
Other protocol-defined criteria apply.
Exclusion Criteria:
1. History of malignancy other than non-melanoma skin cancer or carcinoma in situ
(e.g., cervix, bladder, breast) unless disease-free for at least 3 years.
Participants who have received therapy for a prior malignancy within the prior 3
years, e.g., in the adjuvant setting, are not excluded
2. Active central nervous system (CNS) involvement by malignancy on magnetic resonance
imaging (MRI) or by lumbar puncture. Participants with prior evidence of brain
metastasis treated at least 8 weeks prior to enrollment will not be excluded for
participation if CNS disease is deemed stable at the time of study enrolment
3. History of cardiac lymphoma involvement
4. Ongoing or impending oncologic emergency (e.g., tumor mass effect, tumor lysis
syndrome)
5. Received the following therapies in the specified time frame prior to
enrollment/leukapheresis
1. Any systemic therapy within 2 weeks
2. Any systemic inhibitory/stimulatory immune checkpoint molecule therapy within 3
half-lives prior to enrollment (e.g., ipilimumab, nivolumab, pembrolizumab,
atezolizumab, OX40 agonists, 4-
1BB agonists)
3. Fludarabine within 12 weeks
4. Alemtuzumab, bendamustine or antithymocyte globuline (ATG) within 6 months
5. Any T cell engager/bispecific antibody therapy such as CD20/CD3 or CD19/CD3
bispecific antibodies within 4 weeks
6. Any experimental therapy within 4 weeks or 5 half-lives (whichever is shorter)
6. Received radiation therapy within 3 weeks prior to enrollment
7. Experiencing non-hematologic toxicities due to prior therapy (stable and recovered
to grade ≤ 1 or non- clinically significant toxicities such as alopecia are allowed)
8. History of allogeneic stem cell or solid organ transplantation
9. Receipt of autologous stem cell transplantation within 6 weeks prior to enrollment
10. History of prior genetically modified cell therapy other than a product targeting
CD19 with an FMC63-based CAR (e.g., axicabtagene ciloleucel (axi-cel, YESCARTA®),
tisagenlecleucel (tisa-cel, KYMRIAH®), or lisocabtagene maraleucel (liso-cel,
BREYANZI®). For all other CAR T cell therapy treatments, discussion with the
Sponsor's Medical Monitor is required
11. Primary immunodeficiency
12. History of autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic
lupus) resulting in end organ injury or requiring systemic
immunosuppression/systemic disease modifying agents within the last 2 years.
Participants who have other autoimmune condition(s) considered to be associated with
underlying malignancy may be enrolled in the study after discussion with and
approval of the Medical Monitor.
Other protocol-defined criteria apply.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California-Irvine Medical Center
Address:
City:
Irvine
Zip:
92697
Country:
United States
Status:
Recruiting
Contact:
Last name:
Blake Johnson
Email:
blakej@hs.uci.edu
Investigator:
Last name:
Stefan Ciurea
Email:
Principal Investigator
Facility:
Name:
Cedars-Sinai Medical Center
Address:
City:
Los Angeles
Zip:
90048
Country:
United States
Status:
Recruiting
Contact:
Last name:
Akil Merchant
Phone:
310-423-5706
Email:
Akil.Merchant@cshs.org
Investigator:
Last name:
Akil Merchant
Email:
Principal Investigator
Facility:
Name:
University of California, Los Angeles (UCLA) Medical Center
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christopher M. Hannigan
Phone:
310-825-4493
Email:
CHannigan@mednet.ucla.edu
Investigator:
Last name:
Sara M. Larson
Email:
Principal Investigator
Facility:
Name:
Scripps Clinic
Address:
City:
San Diego
Zip:
92037
Country:
United States
Status:
Recruiting
Contact:
Last name:
James Mason
Email:
Mason.James@scrippshealth.org
Investigator:
Last name:
James Mason
Email:
Principal Investigator
Facility:
Name:
Augusta University Medical Center
Address:
City:
Augusta
Zip:
30912
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amanda Spires
Phone:
706-721-8981
Email:
amspires@augusta.edu
Investigator:
Last name:
Locke Bryan
Email:
Principal Investigator
Facility:
Name:
Indiana Blood and Marrow Transplantation
Address:
City:
Indianapolis
Zip:
46237
Country:
United States
Status:
Recruiting
Contact:
Last name:
Melanie Coleman
Phone:
317-528-7298
Email:
Melanie.Coleman@franciscanalliance.org
Investigator:
Last name:
Felix Mensah
Email:
Principal Investigator
Facility:
Name:
University of Iowa
Address:
City:
Iowa City
Zip:
52242
Country:
United States
Status:
Recruiting
Contact:
Last name:
Umar Farooq
Phone:
319-356-1616
Email:
umar-farooq@uiowa.edu
Investigator:
Last name:
Umar Farooq
Email:
Principal Investigator
Facility:
Name:
University of Louisville Brown Cancer Center
Address:
City:
Louisville
Zip:
40202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mohamed Hegazi
Phone:
502-562-3367
Email:
mohamed.hegazi@louisville.edu
Investigator:
Last name:
Mohamed Hegazi
Email:
Principal Investigator
Facility:
Name:
University of New Mexico Comprehensive Cancer Center
Address:
City:
Albuquerque
Zip:
87131
Country:
United States
Status:
Recruiting
Contact:
Last name:
Valerie Parks
Phone:
404-925-0390
Email:
Vparks@salud.unm.edu
Investigator:
Last name:
Matthew L. Fero
Email:
Principal Investigator
Facility:
Name:
Montefiore Medical Center
Address:
City:
Bronx
Zip:
10461
Country:
United States
Status:
Recruiting
Contact:
Last name:
Dennis Cooper
Email:
decooper@montefiore.org
Investigator:
Last name:
Dennis Cooper
Email:
Principal Investigator
Facility:
Name:
University of Cincinnati (UC) Physicians Company, LLC
Address:
City:
Cincinnati
Zip:
45267
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tahir Latif
Phone:
513-558-2115
Email:
tahir.latif@uc.edu
Investigator:
Last name:
Tahir Latif
Email:
Principal Investigator
Facility:
Name:
Baylor University Medical Center
Address:
City:
Dallas
Zip:
75246
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nebu Koshy
Email:
Nebu.Koshy@BSWHealth.org
Investigator:
Last name:
Nebu Koshy
Email:
Principal Investigator
Facility:
Name:
Huntsman Cancer Institute
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lindsay Gilstrap
Phone:
801-213-5652
Email:
Lindsey.Gilstrap@hci.utah.edu
Investigator:
Last name:
Boyu Hu
Email:
Principal Investigator
Facility:
Name:
Intermountain Healthcare
Address:
City:
Salt Lake City
Zip:
84143
Country:
United States
Status:
Recruiting
Contact:
Last name:
Bradley Hunter
Phone:
801-408-1819
Email:
Brad.Hunter@imail.org
Investigator:
Last name:
Bradley Hunter
Email:
Principal Investigator
Facility:
Name:
Virginia Commonwealth University-Massey Cancer Center
Address:
City:
Richmond
Zip:
23298
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kristin Lantis
Phone:
804-628-6430
Email:
masseybmt@vcu.edu
Investigator:
Last name:
William Clark
Email:
Principal Investigator
Start date:
May 9, 2023
Completion date:
December 1, 2029
Lead sponsor:
Agency:
ImmPACT Bio
Agency class:
Industry
Source:
ImmPACT Bio
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05826535