BAFFR-targeting CAR T Cells for Patients With Relapsed or Refractory B-NHL
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|ClinicalTrials.gov Identifier: NCT05370430|
Recruitment Status : Recruiting
First Posted : May 11, 2022
Last Update Posted : October 20, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma||Biological: BAFFR-CAR T cells||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)|
|Actual Study Start Date :||June 13, 2022|
|Estimated Primary Completion Date :||July 13, 2025|
|Estimated Study Completion Date :||June 13, 2026|
Experimental: B-cell activating factor receptor-Chimeric antigen receptor T cells [BAFFR-CAR T cells]
BAFFR-CAR T cells in participants with r/r B-NHL
Biological: BAFFR-CAR T cells
First-in-human trial examining the safety and preliminary efficacy of BAFFR-CAR T cells in participants with r/r B-NHL
- Incidence of adverse events [ Time Frame: Up to 1 year post treatment ]Assess the safety of administering BAFFR-CAR T cells in participants with relapsed or refractory (r/r) B-cell Non-Hodgkin's Lymphoma (B-NHL) and it's subtypes. Toxicity will be graded per Common Terminology Criteria for Adverse Events version 5.0, Cytokine Release Syndrome (CRS) and neurotoxicity which use the American Society for Transplantation and Cellular Therapy Consensus Criteria (ASTCT) and Graft versus Host Disease (GVHD) criteria. Toxicities will be followed from the start of lymphodepletion until the end of the study.
- Maximum Tolerated Dose (MTD) [ Time Frame: Up to 1 year post treatment ]Determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of BAFFR-CAR T cells. Toxicity will be graded per Common Terminology Criteria for Adverse Events version 5.0, Cytokine Release Syndrome (CRS) and neurotoxicity which use the American Society for Transplantation and Cellular Therapy Consensus Criteria (ASTCT) and Graft versus Host Disease (GVHD) criteria. Toxicities will be followed from the start of lymphodepletion until the end of the study.
- Disease Response [ Time Frame: Up to 1 year post treatment ]Defined as achieving a best response of complete response or partial response per Lugano Criteria
- Minimal Residual Disease (MRD) [ Time Frame: Up to 1 year post treatment ]Negative MRD is defined by malignant cells < 0.01% by flow cytometry or clonoSEQ.
- B Cell Quantification [ Time Frame: Up to 1 year post treatment ]Measured by flow cytometry
- Progression-free survival (PFS) [ Time Frame: From CAR T cell infusion to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed up to 15 years. ]Kaplan-Meier product limit method with log-log transformation for the confidence interval will be used to estimate PFS.
- Overall Survival (OS) [ Time Frame: From the day of BAFFR-CAR T cell infusion to death from any cause assessed, up to 15 years. ]Kaplan-Meier product limit method with log-log transformation for the confidence interval will be used to estimate OS.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 1. Documented informed consent of the participant and/or legally authorized representative.
- 2. Agreement to allow the use of archival tissue from diagnostic tumor biopsies If unavailable, exceptions may be granted with Study PI approval.
- 3. Age: ≥ 18 years
- 4. ECOG ≤ 2
5. Histologically confirmed Mantle Cell Lymphoma (MCL)
- Evidence of positive BAFF-R expression on the MCL cells at the time of enrollment is required. Archival tissue is allowed if there is a significant safety risk for a repeat biopsy or if the lymphoma site is not accessible.
- Subjects with other relapsed or refractory BAFFR+ B cell lymphoma with no standard of care options are allowed during initial dose escalation phase, not the dose expansion phase.
6. Relapsed/refractory disease after failure of at least 1 prior regimen.
- Participants who have primary refractory MCL (with or without prior BTK inhibitor) defined as lymphoma did not respond to a first line therapy or the response did not last longer than 6 months from an initial response, or
- Participants who have relapsed MCL defined as recurrence of disease after an initial response lasting longer than 6 months, must have had at least 1 prior regimen that must include a BTK inhibitor, or
- Participants with newly diagnosed MCL without standard of care (SOC) options (e.g., TP53 mutation, ineligible for intensive chemotherapy) are eligible after discussion with PI.
- 7. Measurable disease by CT scan (≥1.5 cm) or evidence of blood, gastrointestinal, skin, bone marrow or spleen involvement
- 8. Prior CAR T cell therapy is allowed if at least 90 days has elapsed prior to leukapheresis procedure
- 9. Fully recovered from the acute toxic effects (except alopecia) to ≤ Grade 1 to prior anti-cancer therapy
- 10. No known contraindications to leukapheresis, steroids or tocilizumab.
- 11. Total bilirubin ≤ 1.5 X ULN (unless has Gilbert's disease), then ≥ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN)
- 12. AST < 3 x ULN
- 13. ALT < 3 x ULN
- 14. Creatinine clearance of ≥ 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula
- 15. Left ventricular ejection fraction (LVEF) ≥ 45% Note: To be performed within 28 days prior to start of protocol therapy.
- 16. QTc ≤ 480 ms Note: To be performed within 28 days prior to start of protocol therapy.
- 17. O2 saturation > 91% on room air.
18. Seronegative for HIV Ag/Ab combo, HCV*, active HBV (Surface Antigen Negative)
*If seropositive for HIV, HCV or HBV (surface antigen or core antibody positive), nucleic acid quantitation must be performed. Viral load must be undetectable.
19. Women of childbearing potential (WOCBP): negative urine or serum pregnancy test.
*If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
20. Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy.
- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only).
- 1. Prior allogeneic stem cell transplant.
- 2. Autologous stem cell transplant within 90 days at the time of enrollment.
- 3. Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. Physiologic replacement of steroids (i.e., prednisone ≤ 7.5 mg/day or hydrocortisone ≤ 20 mg/day) is allowed. During study participation, participants may receive systemic corticosteroids as needed for treatment-emergent comorbid conditions.
- 4. Cardiac lymphoma involvement
- 5. Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression
- 6. Auto-immune disease or condition requiring systemic immunosuppressant therapy, including uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
- 7. Primary immunodeficiency
- 8. Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification.
- 9. History of clinically significant arrhythmia. Paroxysmal atrial fibrillation or flutter that is stable on medical management at least 2 weeks prior to enrollment is allowed.
- 10. History or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder.
- 11. History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent, including lymphodepletion agents and tocilizumab.
- 12. History of stroke or intracranial hemorrhage within 6 months of enrollment.
- 13. History of venous thrombotic embolism (VTE) within 6 months of enrollment with exception of central line associated VTE.
- 14. History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for ≥ 3 years.
- 15. Clinically significant uncontrolled illness.
- 16. Active systemic uncontrolled infection requiring antimicrobials.
- 17. Active CNS MCL or History of CNS MCL within 3 months prior to screening
- 18. Females only: Pregnant or breastfeeding i. Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
- 19. Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05370430
|Contact: Hazel (Ting-Ying) Cheng, PhDfirstname.lastname@example.org|
|Contact: Katrin Tiemann, PhDemail@example.com|
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Elizabeth Budde, MD|
|Contact: Katrin Tiemann, PhD|
|Principal Investigator:||Elizabeth Budde, MD||City of Hope Medical Center|
|Responsible Party:||PeproMene Bio, Inc.|
|Other Study ID Numbers:||
PMB-BAFFR-102 ( Other Identifier: PeproMeneBio )
|First Posted:||May 11, 2022 Key Record Dates|
|Last Update Posted:||October 20, 2022|
|Last Verified:||October 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Relapsed or Refractory
Mantle Cell Lymphoma
BAFFR-CAR T cells
B-cell Non-Hodgkin's Lymphoma
Neoplasms by Histologic Type
Immune System Diseases