Clinical trial NCT05885464: A Study Evaluating the Safety and Efficacy of BEAM-201 in Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL) or T-Cell Lymphoblastic Lymphoma (T-LL)
Official title: A Phase 1/2, Dose-Exploration and Dose-Expansion Study Evaluating the Safety and Efficacy of Multiplex Base-Edited, Allogeneic Anti-CD7 CAR-T Cells (BEAM-201) in Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL) or T-Cell Lymphoblastic Lymphoma (T-LL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Lymphoblastic Lymphoma
T-Cell Lymphoblastic Leukemia/Lymphoma
Lymphoblastic Leukemia
Keywords: Lymphoblastic Leukemia
Lymphoblastic Lymphoma
Base editing
CAR-T
Lead sponsor: Beam Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2023-06-02
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The maximum number of patients for this study is approximately 102 patients:

* 36 patients in the Phase 1 dose exploration
* approximately 12 patients in the Phase 1 dose-expansion cohorts
* 6 patients in the pediatric cohort
* approximately 48 patients in the Phase 2 cohort.
Primary purpose: TREATMENT

Brief summary: This is a Phase 1/2, multicenter, open-label study to evaluate the safety and efficacy of BEAM-201 in patients with relapsed/refractory T-ALL or T-LL. This study consists of Phase 1 dose-exploration cohorts, Phase 1 dose-expansion cohort(s), a Phase 1 pediatric cohort (will enroll patients ages 1 to \< 12 years), and a Phase 2 cohort.


Eligibility criteria: Key Inclusion Criteria:

1. Ages 18 to ≤ 50 years.
2. Ages ≥ 1 year to \< 18 years, after health authority approval.
3. T-ALL/T-LL that is CD7-positive (defined as at least 20% of blasts positive for CD7 by flow cytometry or immunohistochemistry based on assessment of the study site's CLIA \[Clinical Laboratory Improvement Amendments of 1988\] certified facility) in second or greater relapse, first relapse post-transplant relapse, 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 at screening 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-LL on lymph node biopsy after second CR; OR
      * Any detectable disease post-allogeneic transplant with biopsy confirmed evidence of T-LL on lymph node biopsy
   2. Refractory disease, defined as:

      * Primary refractory T-ALL or T-LL, defined as failure to achieve CR after induction chemotherapy, per investigator assessment and based on biopsy-confirmed evidence of residual T-ALL or T-LL; OR
      * Relapsed, refractory disease, defined as \> 5% BM blasts or biopsy-confirmed evidence of residual TLL 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. 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.

Key Exclusion Criteria:

1. CNS involvement meeting any of the following criteria: CNS-3 disease, progressive CNS involvement despite therapy, CNS parenchymal or cranial nerve lesions on imaging.
2. Clinically active CNS dysfunction or known history of irreversible neurological toxicity related to prior antileukemic therapy.
3. Receipt of prior CD7 targeted therapy.
4. Systemic antileukemic therapy intended to induce or maintain remission within 14 days prior to completion of screening.

Primary outcomes:
measure: Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-related adverse events, including serious adverse events (SAEs) and dose-limiting toxicities (DLTs; in Phase 1 only)
timeFrame: Through study completion, an average of 25 months
measure: Overall response rate as defined as proportion of T-ALL patients achieving complete response (CR) or complete response with incomplete hematologic recovery (CRi) or T-LL patients achieving CR or PR at any point after BEAM-201 infusion
timeFrame: From treatment with BEAM-201 through study completion
Secondary outcomes:
measure: Proportion of patients who achieve MRD negative response (defined as < 0.1%) by flow cytometry or next generation sequencing (NGS) in patients achieving morphologic response
timeFrame: Starting at Day 28 and multiple time points up to Month 24
measure: Proportion of patients treated with BEAM-201 deemed appropriate for HSCT based on investigator assessment of clinical response
timeFrame: Through study completion, an average of 25 months
measure: Duration of Response (DOR)
timeFrame: Through study completion, an average of 25 months
measure: Relapse-free survival (RFS)
timeFrame: Through study completion, an average of 25 months
measure: Overall survival
timeFrame: Through study completion, an average of 25 months
measure: Relapse-related mortality
timeFrame: Through study completion, an average of 25 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Fairway
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Dana Farber and Boston Children's Hospital
state: Massachusetts
city: Cleveland
country: United States
facility: Cleveland Clinic- Taussig Cancer Center
state: Ohio
city: Portland
country: United States
facility: OHSU Knight Cancer Institute Hematology Oncology
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon- TriStar Bone Marrow Transplant
state: Tennessee
city: San Antonio
country: United States
facility: Methodist Hospital - Texas Transplant Institute
state: Texas
Study officials:
References: