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NCT06934382 | RECRUITING | T-Cell Acute Lymphoblastic Leukemia/Lymphoma

Anti-CD7 CAR-T Cells in Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia or Lymphoma
Sponsor:

Stephan Grupp MD PhD

Information provided by (Responsible Party):

Stephan Grupp MD PhD

Brief Summary:

This will be a Phase 1, open-label study to evaluate the safety and efficacy of BEAM-201 in patients with R/R T-ALL or T-LLy. BEAM-201 is an allogeneic anti-CD7 CART therapy.

Condition or disease

T-Cell Acute Lymphoblastic Leukemia/Lymphoma

Intervention/treatment

Allogeneic anti-CD7 CAR-T cells (BEAM-201)

Phase

PHASE1

Detailed Description:

Despite favorable outcomes in newly diagnosed patients, approximately 20% of pediatric and young adult T-ALL patients and 40% of adult patients will have refractory disease or will relapse within 2 years of their initial diagnosis. Survival rates of patients with relapsed disease remain below 35%. For recurrent disease, allogeneic hematopoietic stem cell transplant (HSCT) is the only known potentially curative treatment. However, a prerequisite to HSCT is obtaining a complete remission, which remains a significant challenge as only 40 to 50% of patients achieve a second remission with current reinduction regimens with salvage rates even lower for patients with disease that is refractory to first-line chemotherapy. BEAM-201 is an allogeneic anti-CD7 CAR T cell product that has shown promising early evidence of efficacy, with 3 out of 4 adult T-ALL patients infused had a CRi/CR ≥28 days after infusion. Safety of BEAM-201 has been favorable and consistent with known adverse events associated with other CAR T cell therapies. Given the current treatment landscape of T-ALL/T-LLy, promising clinical experience with BEAM-201, and that \>98% of T-ALL cases highly and homogenously express CD7 protein on the surfaces of their lymphoblasts, the investigators think there is compelling rationale in further investigating the safety and efficacy of BEAM-201 in pediatric patients.

Study Type : INTERVENTIONAL
Estimated Enrollment : 33 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : A Phase 1 Study of Allogeneic Anti-CD7 CAR-T Cells (BEAM-201) in Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia (T-ALL) or T-cell Lymphoblastic Lymphoma (T-LLy)
Actual Study Start Date : 2025-04-29
Estimated Primary Completion Date : 2029-05-30
Estimated Study Completion Date : 2031-05-30

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 0 Years to 29 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
Inclusion Criteria
  • 1. Ages 0 to 29 years.
  • 2. T-ALL/T-LLy in second or greater relapse, first relapse post-transplant, or chemotherapy-refractory disease. Specifically
    • * Second or greater relapse or post-transplant relapse, defined as
      • * BM with ≥ 5% lymphoblasts by morphologic assessment or evidence of extramedullary disease after second documented CR; OR
      • * Flow cytometric confirmation of relapsed T-ALL of at least 0.1% after second CR documented to have been MRD negative \< 0.1%; OR
      • * Any detectable relapsed disease post-allogeneic HSCT with flow cytometric confirmation of T-ALL of at least 0.1%; OR
      • * Biopsy confirmed evidence of relapsed T-LLy after second CR; OR
      • * Any detectable disease post-allogeneic transplant with biopsy confirmed evidence of T-LLy
      • * Refractory disease, defined as
        • * Primary refractory T-ALL or T-LLy, defined as failure to achieve CR after induction chemotherapy, per investigator assessment and based on biopsy- or MRD-confirmed evidence of residual T-ALL or T-LLy; OR
        • * Relapsed, refractory disease, defined as \> 0.1 % MRD or morphologic evidence of disease or evidence of residual T-LLy after 1 course of re-induction chemotherapy for patients who have relapsed after previously achieving a CR
        • NOTE: Patients with mixed phenotype acute leukemia with T cell dominant phenotype may be enrolled if the aforementioned criteria are met.
        • 3. Documentation of CD7 expression on leukemic blasts (defined as at least 20% of blasts positive for CD7 by flow cytometry or immunohistochemistry).
        • 4. Patients with prior or current history of CNS3 disease will be eligible if CNS disease is responsive to therapy
        • 5. Eligible for myeloablative conditioning for and allogeneic HSCT based on the investigator's assessment with an available donor identified by a FACT accredited transplant center.
        • 6. Lansky Performance Status (ages \< 16 years at time of consent) or Karnofsky Performance Status (KPS) (ages ≥ 16 years at time of consent) score of ≥ 50.
        • 7. Patients of childbearing potential must have a negative urine or serum pregnancy test at screening.
        • 8. Patients who are sexually active and of reproductive potential must agree to use an acceptable form of highly effective contraception from consent to 12 months after BEAM 201 infusion.
        • 9. Patients (ages ≥ 18 years) or parent/legal guardians (for patients ages \< 18 years) must provide signed, written informed consent according to local IRB and institutional requirements.
        Exclusion Criteria
        • 1. CNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
        • 2. Clinically active CNS dysfunction or known history of irreversible central neurological toxicity related to prior antileukemic therapy.
        • 3. Receipt of prior CD7 targeted therapy.
        • 4. Systemic antileukemic therapy intended to induce remission within 14 days prior to completion of screening.
        • 5. Radiation therapy within 2 weeks prior to completion of screening, other than prophylaxis for CNS disease.
        • 6. Acute GVHD that is grade ≥ 2 and requiring systemic immunosuppression (corticosteroids), or chronic GVHD that is mild, moderate, or severe and requiring systemic immunosuppression (corticosteroids). Grade 1 acute GVHD not requiring immunosuppression is allowable.
        • 7. Undergone HSCT within 90 days prior to completion of screening (or donor leukocyte infusion, if received within 30 days prior to completion of screening).
        • 8. Evidence of organ dysfunction including
          • * Serum ALT ≥ 5 × ULN for age
          • * Total bilirubin ≥ 3 × ULN for age
          • * Serum creatinine that exceeds the maximum values listed in the protocol.
          • * Any of the following cardiac criteria
            • i. Atrial fibrillation/flutter (not including isolated episodes that responded to medical management) ii. Myocardial infarction within the last 12 months iii. QT interval corrected for heart rate using Fridericia's method (QTcF) \> 480 msec iv. Cardiac echocardiography (ECHO) with left ventricular shortening fraction (LVSF) \< 30% or left ventricular ejection fraction (LVEF) \< 50% or clinically significant pericardial effusion v. Cardiac dysfunction NYHA (New York Heart Association) III or IV
            • * A minimum level of pulmonary reserve defined as \>Grade 1 dyspnea and \>Grade 3 hypoxia; DLCO 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the investigator
            • 9. Positive serology for
              • * Human immunodeficiency virus (HIV) (HIV-1 or HIV2)
              • * Human T-cell lymphotropic virus (HTLV) (HTLV-1 or HTLV-2)
              • * Hepatitis B (positive surface Ag or positive core Ab unless Hep B DNA negative by polymerase chain reaction \[PCR\])
              • * Hepatitis C (if hepatitis C virus \[HCV\] antibody positive) must be HCV RNA PCR negative. Patients with sustained viral response \> 12 weeks following antiviral therapy are eligible as long as no history of hepatic cirrhosis is present.
              • 10. Uncontrolled, active bacterial, viral, or fungal infection.
              • 11. Any other condition that would make the patient ineligible for HSCT as determined by the investigator.
              • 12. Patients with an autoimmune disorder requiring systemic immunosuppressive therapy that cannot be safely withheld for 3 months.
              • 13. Concurrent use of systemic corticosteroids for diagnoses unrelated to T-ALL/T-LLy is prohibited, with exception of physiologic corticosteroid replacement therapy treatment for adrenal insufficiency.
              • 14. Known primary immunodeficiency or BM failure syndrome.
              • 15. Pregnant or breastfeeding.
Anti-CD7 CAR-T Cells in Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia or Lymphoma

Location Details

NCT06934382

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Locations

RECRUITING

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104