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Study of IMPT-314 in R/R Aggressive B-cell

Primary Purpose

Relapsed Non-Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
IMPT-314
Sponsored by
ImmPACT Bio
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed Non-Hodgkin Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age 18 years or older Willing and able to provide written informed consent Histologically confirmed aggressive NHL, including the following types defined by the World Health Organization (WHO) 2017: DLBCL not otherwise specified (NOS) DLBCL arising from follicular lymphoma Primary mediastinal (thymic) large B-cell lymphoma High-grade large B-cell lymphoma with or without MYC and BCL2 and/or BCL6 rearrangement Received at least 2 prior lines 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 Relapsed or refractory disease, defined by the following: Disease progression after last regimen (including salvage therapy after autologous stem cell transplantation [ASCT]), or Refractory disease is defined failure to achieve a PR or CR to the last regimen 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 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Absolute neutrophil count (ANC) ≥ 1000/uL Other protocol-defined criteria apply. Exclusion Criteria: 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 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 they are deemed under control at the time of study enrollment History of cardiac lymphoma involvement Ongoing or impending oncologic emergency (e.g., tumor mass effect, tumor lysis syndrome) Received any systemic therapy within two weeks prior to enrollment/leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy. Received any systemic inhibitory/stimulatory immune checkpoint molecule therapy within less than 3 half-lives prior to enrollment (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4- 1BB agonists) Received radiation therapy within 3 weeks prior to enrollment Experiencing toxicities due to prior therapy (stable and recovered to grade ≤ 1 or non- clinically significant toxicities such as alopecia are allowed) History of allogeneic stem cell transplantation Receipt of autologous stem cell transplantation within 6 weeks prior to enrollment History of prior CAR therapy or other genetically modified T cell therapy Primary immunodeficiency 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 Other protocol-defined criteria apply.

Sites / Locations

  • University of California, Los Angeles (UCLA) Medical CenterRecruiting
  • University of Iowa
  • University of Cincinnati (UC) Physicians Company, LLC
  • Huntsman Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Phase I Dose Level I cohort

Phase I Dose Level II cohort

Phase II single group

Arm Description

Phase I 3+3 design Dose level 1: 1×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window

Phase I 3+3 design Dose level 2: 3×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window

Single dose determined during Phase I.

Outcomes

Primary Outcome Measures

Phase I: Incidence of DLTs and other treatment-emergent adverse events (TEAEs)
Phase I: Investigator-assessed complete response (CR) rate
Phase I: Proportion of enrolled participants who receive the target dose
Phase II: Complete response based on investigator assessment per the Lugano classification

Secondary Outcome Measures

Full Information

First Posted
March 24, 2023
Last Updated
May 17, 2023
Sponsor
ImmPACT Bio
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1. Study Identification

Unique Protocol Identification Number
NCT05826535
Brief Title
Study of IMPT-314 in R/R Aggressive B-cell
Official Title
A Phase 1/2 Multi-center Study Evaluating the Safety and Efficacy of IMPT-314, a CD19/20 Bispecific Chimeric Antigen Receptor (CAR) T Cell Therapy in Participants With Relapsed or Refractory Aggressive B-Cell Non-Hodgkin Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 9, 2023 (Anticipated)
Primary Completion Date
June 1, 2025 (Anticipated)
Study Completion Date
December 1, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ImmPACT Bio

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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. Up to 30 patients will be enrolled in dose finding Phase 1 part of the study, which will determine the recommended phase 2 dose. Phase 2 will enroll 20 additional participants 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed Non-Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Dose finding Phase I followed by a single group Phase II part. Two Phase I dose levels and one Phase II dose level.
Masking
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.
Allocation
Non-Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase I Dose Level I cohort
Arm Type
Experimental
Arm Description
Phase I 3+3 design Dose level 1: 1×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window
Arm Title
Phase I Dose Level II cohort
Arm Type
Experimental
Arm Description
Phase I 3+3 design Dose level 2: 3×10e8 (± 20%) IMPT-314 cells Single dose/infusion during 28 day window
Arm Title
Phase II single group
Arm Type
Experimental
Arm Description
Single dose determined during Phase I.
Intervention Type
Drug
Intervention Name(s)
IMPT-314
Intervention Description
CAR T-cell therapy
Primary Outcome Measure Information:
Title
Phase I: Incidence of DLTs and other treatment-emergent adverse events (TEAEs)
Time Frame
Baseline to Month 24
Title
Phase I: Investigator-assessed complete response (CR) rate
Time Frame
Baseline to Month 24
Title
Phase I: Proportion of enrolled participants who receive the target dose
Time Frame
Baseline to Month 24
Title
Phase II: Complete response based on investigator assessment per the Lugano classification
Time Frame
Baseline to Month 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 years or older Willing and able to provide written informed consent Histologically confirmed aggressive NHL, including the following types defined by the World Health Organization (WHO) 2017: DLBCL not otherwise specified (NOS) DLBCL arising from follicular lymphoma Primary mediastinal (thymic) large B-cell lymphoma High-grade large B-cell lymphoma with or without MYC and BCL2 and/or BCL6 rearrangement Received at least 2 prior lines 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 Relapsed or refractory disease, defined by the following: Disease progression after last regimen (including salvage therapy after autologous stem cell transplantation [ASCT]), or Refractory disease is defined failure to achieve a PR or CR to the last regimen 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 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Absolute neutrophil count (ANC) ≥ 1000/uL Other protocol-defined criteria apply. Exclusion Criteria: 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 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 they are deemed under control at the time of study enrollment History of cardiac lymphoma involvement Ongoing or impending oncologic emergency (e.g., tumor mass effect, tumor lysis syndrome) Received any systemic therapy within two weeks prior to enrollment/leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy. Received any systemic inhibitory/stimulatory immune checkpoint molecule therapy within less than 3 half-lives prior to enrollment (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4- 1BB agonists) Received radiation therapy within 3 weeks prior to enrollment Experiencing toxicities due to prior therapy (stable and recovered to grade ≤ 1 or non- clinically significant toxicities such as alopecia are allowed) History of allogeneic stem cell transplantation Receipt of autologous stem cell transplantation within 6 weeks prior to enrollment History of prior CAR therapy or other genetically modified T cell therapy Primary immunodeficiency 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 Other protocol-defined criteria apply.
Facility Information:
Facility Name
University of California, Los Angeles (UCLA) Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christopher M. Hannigan
Phone
310-825-4493
Email
CHannigan@mednet.ucla.edu
First Name & Middle Initial & Last Name & Degree
Sara M. Larson
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Umar Farooq
Phone
319-356-1616
Email
umar-farooq@uiowa.edu
First Name & Middle Initial & Last Name & Degree
Umar Farooq
Facility Name
University of Cincinnati (UC) Physicians Company, LLC
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tahir Latif
Phone
513-558-2115
Email
tahir.latif@uc.edu
First Name & Middle Initial & Last Name & Degree
Tahir Latif
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lindsay Gilstrap
Phone
801-213-5652
Email
Lindsey.Gilstrap@hci.utah.edu
First Name & Middle Initial & Last Name & Degree
Boyu Hu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of IMPT-314 in R/R Aggressive B-cell

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