Clinical Trials /

Leukemia-Specific Immune Cells (BAFFR- CAR T Cells) for the Treatment of Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

NCT04690595

Description:

A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients with Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Leukemia-Specific Immune Cells (BAFFR- CAR T Cells) for the Treatment of Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia
  • Official Title: A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: PMB-101
  • NCT ID: NCT04690595

Conditions

  • Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
BAFFR-CAR T cellsBAFFR-CAR T cells

Purpose

A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients with Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

Detailed Description

      This phase I trial evaluates the side effects and best dose of BAFFR-CAR T cells in treating
      patients with B-cell Acute Lymphoblastic Leukemia 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.
    

Trial Arms

NameTypeDescriptionInterventions
BAFFR-CAR T cellsExperimentalB-cell activating factor receptor-Chimeric antigen receptor T cells
  • BAFFR-CAR T cells

Eligibility Criteria

        Inclusion 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. If unavailable, exceptions may be granted with study PI approval.

          4. Age ≥ 18 years.

          5. ECOG ≤ 2.

          6. Life expectancy ≥ 16 weeks.

          7. Histologically confirmed B-ALL or B-cell lymphoblastic lymphoma

          8. Relapsed/refractory disease after failure of ≥ 2 prior lines of therapy.

          9. Evidence of active BAFF-R expression at the time of enrollment.

         10. Recovered to ≤ Grade 1 from the acute toxic effects (except alopecia) of prior
             anti-cancer therapy.

         11. No known contraindications to leukapheresis, steroids or tocilizumab.

         12. Ineligible for or failed prior CD19-targeted immunotherapy (e.g., blinatumomab or
             CD19-CAR T cells).

         13. For participants to be eligible for the trial following prior CD19-CAR T cell therapy
             at least 90-days has elapsed since participant received last CD19-CAR T cell therapy.

         14. Participants with CNS involvement by leukemia (CNS2 and asymptomatic CNS3) may be
             considered eligible after discussions with the study team.

         15. Total serum bilirubin ≤2.0 mg/dL (unless has Gilbert's disease or leukemia involvement
             of the liver, then ≤3.0)

         16. AST ≤2.5 x ULN

         17. ALT ≤ 2.5 x ULN

         18. Creatinine clearance of ≥ 50 mL/min per 24-hour urine test or the Cockcroft-Gault
             formula

         19. Left ventricular ejection fraction (LVEF) ≥ 50%

         20. O2 saturation ≥ 92% on room air.

         21. Seronegative for HIV Ag/Ab combo, HCV*, and active HBV (Surface Antigen Negative)

         22. *If positive, Hepatitis C RNA quantitation must be performed and must be undetectable.

         23. 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

         24. 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).

        Exclusion Criteria:

          1. Autologous/allogeneic stem cell transplant within 100 days at the time of enrollment.

          2. 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 (prednisone ≤ 7.5 mg /day or equivalent) is allowed

          3. Auto-immune disease or active GVHD requiring systemic immunosuppressant therapy.

          4. Class III/IV cardiovascular disability according to the New York Heart Association
             (NYHA) Classification.

          5. Subjects with clinically significant arrhythmia or arrhythmias not stable on medical
             management within 2 weeks of enrollment.

          6. Subjects with a known history or prior diagnosis of optic neuritis or other
             immunologic or inflammatory disease affecting the central nervous system, including
             seizure disorder.

          7. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to study agent.

          8. Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.

          9. History of stroke or intracranial hemorrhage within 6 months of enrollment.

         10. 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.

         11. Clinically significant uncontrolled illness.

         12. Active systemic uncontrolled infection requiring antibiotics.

         13. Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection.

         14. Females only: Pregnant or breastfeeding.

         15. Any other condition that would, in the investigator's judgment, contraindicate the
             subject's participation in the clinical study due to safety concerns with clinical
             study procedures.

         16. 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 1 year post treatment
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Disease response
Time Frame:Up to 1 year post treatment
Safety Issue:
Description:Defined as complete response [CR], or complete response with incomplete blood count recovery [CRi], or complete response with partial hematological recovery [CRh]. Response will be evaluated using European Leukemia Net (ELN) criteria. Rates and associated 95% binomial exact confidence limits will be estimated (CR/CRi/CRh) rate.
Measure:Minimal residual disease (MRD)
Time Frame:Up to 1 year post treatment
Safety Issue:
Description:Negative MRD is defined by malignant cells < 0.01% by flow cytometry or clonoSEQ.
Measure:B cell frequency
Time Frame:Up to 1 year post treatment
Safety Issue:
Description:Measured by serum IgG level
Measure:Severity of graft-versus-host disease (GVHD) in recipients of prior allogeneic hematopoietic stem cell transplantation
Time Frame:Up to 1 year post treatment.
Safety Issue:
Description:Defined per Keystone criteria for acute GVHD and revised National Institute of Health (NIH) consensus on grading of chronic GVHD.
Measure:Progression-free survival (PFS)
Time Frame:From T cell infusion to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed up to 15 years.
Safety Issue:
Description:Kaplan-Meier product limit method with log-log transformation for the confidence interval will be used to estimate PFS.
Measure:Overall survival (OS)
Time Frame:From the day of BAFFR-CAR T cell infusion to death from any cause assessed, up to 15 years.
Safety Issue:
Description:Kaplan-Meier product limit method with log-log transformation for the confidence interval will be used to estimate OS.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:PeproMene Bio, Inc.

Trial Keywords

  • B cell
  • ALL
  • relapsed or refractory

Last Updated

December 30, 2020