RECRUITING

BAFFR-targeting CAR T Cells for Patients With Relapsed or Refractory B-NHL

Conditions

Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma Relapsed or Refractory Mantle Cell Lymphoma BAFFR-CAR T cells B-cell Non-Hodgkin's Lymphoma B-NHL BAFFR MCL LBCL

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients with Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)

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)

Quick Facts

Study Start:2022-06-13

Study Completion:2028-06-13

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05370430

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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 * 3. Age: ≥ 18 years * 4. ECOG ≤ 2 * 5. Histologically confirmed diagnosis of B-NHL, as follows: * Large B-cell lymphoma (LBCL) patients including the following types defined by World Health Organization (WHO) 2016 classification - DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBCL) with or without MYC and BCL2 and/or BCL6 rearrangement, transformed follicular lymphoma (tFL), and transformed marginal zone lymphoma (tMZL) - as well as follicular lymphoma (FL) Grade 3b, who have received at least 2 prior lines of standard therapy (described in NCCN guidelines), which must contain an anti-CD20 targeted agent (unless documented CD20 negative) and an anthracycline. * Mantle Cell Lymphoma (MCL) patients with: * 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 * Newly diagnosed MCL without standard of care (SOC) options (e.g., TP53 mutation, ineligible for intensive chemotherapy) are eligible after discussion with PI. * Follicular lymphoma (FL) Grades 1-3a and marginal zone lymphoma (MZL) patients who are relapsed or refractory to at least one prior systemic treatment regimen which must include an anti-CD20 targeted agent (unless documented CD20 negative), and for whom there is no readily available therapy expected to improve survival (e.g., standard chemotherapy, ASCT). * 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 3 months have elapsed prior to leukapheresis procedure i. If participant received prior CD19-CAR T cells persistence must be evaluated and found to be \<5% 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. Blood counts: * Absolute Neutrophil count (ANC ≥1000 cells/ul)\* * Platelet count ≥75,000/ul. Transfusion with 7 days prior to screening is not allowed\* * Exception: participants with bone marrow involvement do not need to meet this criteria * 13. AST \< 3 x ULN * 14. ALT \< 3 x ULN * 15. Creatinine clearance of ≥ 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula * 16. Left ventricular ejection fraction (LVEF) ≥ 45% Note: To be performed within 28 days prior to start of protocol therapy. * 17. QTc ≤ 480 ms Note: To be performed within 28 days prior to start of protocol therapy. * 18. O2 saturation \> 91% on room air. * 19. Seronegative for HIV Ag/Ab combo, HCV\, active HBV (Surface Antigen Negative) 20. Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. * 21. 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 6 months prior to leukapheresis * 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).

Inclusion Criteria

Exclusion Criteria

* 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
* 3. Age: ≥ 18 years
* 4. ECOG ≤ 2
* 5. Histologically confirmed diagnosis of B-NHL, as follows:
* Large B-cell lymphoma (LBCL) patients including the following types defined by World Health Organization (WHO) 2016 classification - DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBCL) with or without MYC and BCL2 and/or BCL6 rearrangement, transformed follicular lymphoma (tFL), and transformed marginal zone lymphoma (tMZL) - as well as follicular lymphoma (FL) Grade 3b, who have received at least 2 prior lines of standard therapy (described in NCCN guidelines), which must contain an anti-CD20 targeted agent (unless documented CD20 negative) and an anthracycline.
* Mantle Cell Lymphoma (MCL) patients with:
* 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
* Newly diagnosed MCL without standard of care (SOC) options (e.g., TP53 mutation, ineligible for intensive chemotherapy) are eligible after discussion with PI.
* Follicular lymphoma (FL) Grades 1-3a and marginal zone lymphoma (MZL) patients who are relapsed or refractory to at least one prior systemic treatment regimen which must include an anti-CD20 targeted agent (unless documented CD20 negative), and for whom there is no readily available therapy expected to improve survival (e.g., standard chemotherapy, ASCT).
* 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 3 months have elapsed prior to leukapheresis procedure i. If participant received prior CD19-CAR T cells persistence must be evaluated and found to be \<5% 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. Blood counts:
* Absolute Neutrophil count (ANC ≥1000 cells/ul)\*
* Platelet count ≥75,000/ul. Transfusion with 7 days prior to screening is not allowed\*
* Exception: participants with bone marrow involvement do not need to meet this criteria
* 13. AST \< 3 x ULN
* 14. ALT \< 3 x ULN
* 15. Creatinine clearance of ≥ 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula
* 16. Left ventricular ejection fraction (LVEF) ≥ 45% Note: To be performed within 28 days prior to start of protocol therapy.
* 17. QTc ≤ 480 ms Note: To be performed within 28 days prior to start of protocol therapy.
* 18. O2 saturation \> 91% on room air.
* 19. Seronegative for HIV Ag/Ab combo, HCV\*, active HBV (Surface Antigen Negative)
* 20. Women of childbearing potential (WOCBP): negative urine or serum pregnancy test.
* 21. 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 6 months prior to leukapheresis
* 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).

Contacts and Locations

Study Contact

Hazel (Ting-Ying) Cheng, PhD

CONTACT

714-599-8077

hazel.cheng@pepromenebio.com

Hemali Patel

CONTACT

913-574-6176

Hemali.Patel@iconplc.com

Principal Investigator

Elizabeth Budde, MD

STUDY_CHAIR

City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center

Duarte, California, 91010

United States

Collaborators and Investigators

Sponsor: PeproMene Bio, Inc.

Elizabeth Budde, MD, STUDY_CHAIR, City of Hope Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-06-13

Study Completion Date2028-06-13

Study Record Updates

Study Start Date2022-06-13

Study Completion Date2028-06-13

Terms related to this study

Keywords Provided by Researchers

Relapsed or Refractory
Mantle Cell Lymphoma
BAFFR-CAR T cells
B-cell Non-Hodgkin's Lymphoma
B-NHL
BAFFR
MCL
LBCL

Additional Relevant MeSH Terms

Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma