Using anti-CD7 CAR-T cells to treat relapsed or refractory T-Cell leukemia or lymphoma

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)

This study is testing a new CAR-T cell therapy called BEAM-201 to see if it can help young people with tough-to-treat T-Cell leukemia or lymphoma feel better and achieve remission.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 33 (estimated)
• Ages: 0 Years to 29 Years
• Sex: All
• Sponsor: Children's Hospital of Philadelphia (Academic / other)
• Drugs / interventions: chemotherapy, Radiation, CART, CAR T
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT06934382 on ClinicalTrials.gov

What this trial studies

This Phase 1, open-label study evaluates the safety and efficacy of BEAM-201, an allogeneic anti-CD7 CAR T cell therapy, in patients aged 0 to 29 with relapsed or refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL) or T-Cell Lymphoma (T-LLy). The study aims to address the significant challenge of achieving complete remission in patients who have not responded to standard treatments. BEAM-201 has shown promising early results, with a notable percentage of adult patients achieving complete remission after treatment. The study will assess both the safety profile and the potential for this therapy to improve outcomes in a patient population with limited treatment options.

Who should consider this trial

Good fit: Ideal candidates are patients aged 0 to 29 years with T-ALL or T-LLy who are experiencing their second or greater relapse or have chemotherapy-refractory disease.

Not a fit: Patients who are not experiencing relapse or who have not undergone prior chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve remission rates and survival outcomes for young patients with relapsed or refractory T-ALL or T-LLy.

How similar studies have performed: Other studies have shown promising results with CAR-T therapies in similar conditions, indicating a potential for success with this novel approach.

Eligibility criteria

Patients must meet all the following criteria to be eligible for enrollment into the study:

1. 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.
2. Ages 0 to 29 years.
3. T-ALL/T-LLy in second or greater relapse, first relapse post-transplant, or chemotherapy-refractory disease. Specifically:

   1. 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
   2. 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.
4. Documentation of CD7 expression on leukemic or T-LLy blasts (defined as at least 90% of blasts positive for CD7 by flow cytometry or immunohistochemistry).
5. Patients with prior or current history of CNS3 disease will be eligible if CNS disease is responsive to therapy
6. 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.
7. 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.
8. Patients of childbearing potential must have a negative urine or serum pregnancy test at screening.
9. Adequate organ function defined as:

   1. Adequate Serum creatinine based on age/gender
   2. ALT ≤ 5x ULN in the absence of ALL infiltration of the liver
   3. Bilirubin ≤ 3 × ULN for age Note: ALT and/or bilirubin results that exceed this range are acceptable if, in the opinion of the physician-investigator (or as confirmed by liver biopsy), the abnormalities are directly related to ALL infiltration of the liver.
   4. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and \<Grade 3 hypoxia; DLCO ≥40% (corrected for anemia if necessary) if PFTs are clinically appropriate as determined by the investigator.
   5. Cardiac echocardiography (ECHO) with left ventricular shortening fraction (LVSF) ≥ 30% or left ventricular ejection fraction (LVEF) ≥ 50%. In cases where quantitative assessment of LVSF/LVEF is not possible, a statement by the cardiologist that the ECHO shows qualitatively normal ventricular function will suffice
10. 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.

4.2 Exclusion Criteria

Patients who meet any of the following criteria will be disqualified from entering the study:

1. Active hepatitis B or active hepatitis C
2. Active HTLV infection
3. HIV infection
4. Uncontrolled, active bacterial, viral, or fungal infection.
5. CNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
6. Clinically active CNS dysfunction or known history of irreversible central neurological toxicity related to prior antileukemic therapy.
7. Receipt of prior CD7 targeted therapy.
8. Radiation therapy within 2 weeks prior to completion of screening, other than prophylaxis for CNS disease.
9. 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.
10. Undergone HSCT within 90 days prior to completion of screening (or donor leukocyte infusion, if received within 30 days prior to completion of screening).
11. Any other condition that would make the patient ineligible for HSCT as determined by the investigator.
12. Known primary immunodeficiency or BM failure syndrome.
13. Atrial fibrillation/flutter (not including isolated episodes that responded to medical management)
14. Clinically significant pericardial effusion
15. Myocardial infarction within the last 12 months
16. QT interval corrected for heart rate \> 480 msec
17. Cardiac dysfunction NYHA (New York Heart Association) III or IV
18. Patients with an autoimmune disorder requiring systemic immunosuppressive therapy that cannot be safely withheld for 3 months.

    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.
19. Pregnant or breastfeeding

Where this trial is running

Philadelphia, Pennsylvania

• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Caroline Diorio, MD — Children's Hospital of Philadelphia
• Study coordinator: Cell Therapy Intake Team

Conditions T-Cell Acute Lymphoblastic Leukemia/Lymphoma; CART; T-cell leukemia; T-cell lymphoma