Clinical trial NCT05370430: BAFFR-targeting CAR T Cells for Patients with Relapsed or Refractory 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
Keywords: Relapsed or Refractory
Mantle Cell Lymphoma
BAFFR-CAR T cells
B-cell Non-Hodgkin's Lymphoma
B-NHL
BAFFR
MCL
LBCL
Lead sponsor: PeproMene Bio, Inc.
Sponsor class: INDUSTRY
Collaborators: name: City of Hope Medical Center
First posted: 2022-05-11
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: This phase I trial evaluates the side effects and best dose of BAFFR-CAR T cells in treating patients with B-cell Non-Hodgkin's Lymphoma (B-NHL) that has come back (recurrent) or does not respond to treatment (refractory). T cells are infection fighting blood cells that can kill cancer cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize BAFFR, a protein on the surface of cancer cells. These BAFFR-specific T cells may help the body's immune system identify and kill BAFFR+ cancer cells.

Eligibility criteria: Inclusion Criteria:

1. Informed Consent: Signed informed consent by the participant or legally authorized representative.
2. Age \& Performance Status:

   * Age ≥ 18 years
   * ECOG performance status ≤ 2
3. Diagnosis \& Disease Criteria:

   * Histologically confirmed B-NHL, including LBCL, MCL, and FL/MZL subtypes meeting specified prior treatment conditions.
   * BAFF-R expression on lymphoma cells required.
4. Measurable Disease: Tumor ≥1.5 cm on CT/PET scan or evidence of disease in blood, BM, GI, skin, or spleen.
5. Prior CAR T-cell Therapy: Allowed if ≥ 3 months since last treatment and CD19 CAR-T persistence \< 5% before leukapheresis.
6. Organ Function \& Laboratory Criteria:

   * Hematologic: ANC ≥ 1000/μL, Platelets ≥ 75,000/μL (exceptions for BM involvement).
   * Liver Function: Bilirubin ≤ 1.5x ULN (except Gilbert's), AST/ALT \< 3x ULN.
   * Renal Function: CrCl ≥ 50 mL/min.
   * Cardiac \& Pulmonary: LVEF ≥ 45%, QTcF ≤ 480 ms, O₂ saturation \> 91% on room air.
7. Infectious Disease Screening: Seronegative for HIV, active HBV, active HCV (or undetectable viral load if positive).
8. Reproductive Considerations:

   * Negative pregnancy test for females of childbearing potential.
   * Use of effective contraception or abstinence through 3 months post-treatment.

Exclusion Criteria:

1. Prior Therapies \& Transplants:

   * Prior allogeneic SCT.
   * Autologous SCT \< 6 months before leukapheresis.
   * Concurrent systemic steroids or chronic immunosuppressant use.
2. Disease-Specific Exclusions:

   * Cardiac lymphoma involvement.
   * Need for urgent therapy due to tumor-related complications (e.g., bowel obstruction).
3. Medical Conditions:

   * Active autoimmune disease requiring immunosuppressants.
   * Primary immunodeficiency.
   * Cardiac conditions, including NYHA Class III/IV heart disease, arrhythmia, recent MI (≤ 6 months), stroke (≤ 6 months), or significant VTE (≤ 6 months).
   * Neurologic conditions, including prior optic neuritis, CNS inflammatory diseases, or seizure disorders.
   * History of malignancy, unless resected/treated with curative intent or in remission for ≥ 3 years.
   * Uncontrolled systemic infections or active CNS lymphoma.
4. Pregnancy \& Breastfeeding: Females who are pregnant or nursing.
5. Other Considerations:

   * Investigator-determined safety concerns.
   * Potential noncompliance with study procedures.

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 1 year post treatment
measure: Maximum Tolerated Dose (MTD)
timeFrame: The DLT evaluation period is defined as 28 days following BAFFR CAR-T infusion.
Secondary outcomes:
measure: Disease Response
timeFrame: Up to 1 year post treatment
measure: Minimal Residual Disease (MRD)
timeFrame: Up to 1 year post treatment
measure: B Cell Quantification
timeFrame: Up to 1 year post treatment
measure: Progression-free survival (PFS)
timeFrame: 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.
measure: Overall Survival (OS)
timeFrame: From the day of BAFFR-CAR T cell infusion to death from any cause assessed, up to 15 years.
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Charlotte
country: United States
facility: Atrium Health Levine Cancer Institute - Morehead
state: North Carolina
city: Seattle
country: United States
facility: Providence Swedish Cancer Institute
state: Washington
Study officials:
affiliation: City of Hope Medical Center
name: Elizabeth Budde, MD
role: STUDY_CHAIR
References: