IMPT-314 in Aggressive B-Cell Non-Hodgkin Lymphoma

What is the Purpose of this Study?

The purpose of this study is to evaluate experimental gene-modified immune cells called IMPT-314 for the treatment of lymphomas that have either come back after treatment or have stopped responding to treatment. IMPT-314 is a type of drug called a chimeric antigen receptor T cell, also known as a CAR T cell. Researchers aim to examine the safety and side effects of IMPT-314, determine which dosages are safe for people to take, and evaluate how well the study drug destroys cancer cells. A virus will be used to introduce a gene that creates a protein called a chimeric antigen receptor (CAR) on the surface of the T cells, a type of white blood cell that fights infection and eliminates cancer cells. The study will collect and modify some of the patient’s own white blood cells and give them back to the patient in the hope that these cells can then identify and possibly kill cancerous cells.

Eligibility

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:

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 initiating 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 successfully 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 T 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.

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Where can I participate?

Cedars-Sinai Cancer at SOCC : Amy Oppenheim

More about this Clinical Trial

What is the full name of this clinical trial?

A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of IMPT-314, a CD19/20 Bispecific Chimeric Antigen Receptor T Cell Therapy in Participants with Relapsed or Refractory Aggressive B-Cell Non-Hodgkin Lymphoma

Study Details

Disease Type/Condition

Non-Hodgkin's Lymphoma

Principal Investigator

Merchant, Akil

Co-Investigators

David Oveisi, Hannah Lee, Joshua Sasine, Justin Darrah, Noah Merin, Robert Vescio, Ronald Paquette

Age Group

Adult

Phase

I/II

IRB Number

STUDY00002922

ClinicalTrials.gov ID

NCT05826535

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Amy Oppenheim

Phone

+1 310-423-3713

amy.oppenheim@cshs.org