Obecabtagene autoleucel consolidation for newly diagnosed high-risk B-cell acute lymphoblastic leukemia

Phase 2 Study Assessing the Clinical Activity and Safety of Obecabtagene Autoleucel as a Consolidation in Patients With Newly Diagnosed High-risk B-cell Acute Lymphocytic Leukemia (ALL)

This trial will test whether a single infusion of the CAR‑T therapy obecabtagene autoleucel can help keep adults with newly diagnosed high‑risk B‑cell ALL in remission when given after initial chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: CAR-T, CAR T, chimeric antigen receptor
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT07053059 on ClinicalTrials.gov

What this trial studies

This phase 2 interventional trial gives adults with newly diagnosed high‑risk B‑cell ALL a single infusion of anti‑CD19 autologous CAR‑T cells (obecabtagene autoleucel) as consolidation after they achieve first remission with standard chemoimmunotherapy. The primary endpoint is 18‑month event‑free survival (EFS), with secondary endpoints including 24‑month overall survival, rates of persistent MRD negativity by flow cytometry and NGS (and BCR::ABL1 PCR for Ph‑positive patients), and safety. Participants will be monitored for CAR‑T expansion and B‑cell aplasia with scheduled assays up to 12 months post infusion and longer follow‑up for survival and subsequent therapies. Manufacturing and central laboratory testing are performed in collaboration with the CAR‑T developer and certified labs, and the intervention and follow‑up occur at the trial site.

Who should consider this trial

Good fit: Adults (≥18 years) with newly diagnosed high‑risk B‑cell ALL in first remission with <5% bone marrow blasts and at least one specified high‑risk genomic feature or persistent MRD are the intended participants.

Not a fit: Patients with active uncontrolled disease (>5% blasts), significant organ dysfunction or poor performance status, or non‑B‑cell leukemias are unlikely to benefit from this CAR‑T consolidation approach.

Why it matters

Potential benefit: If effective, this approach could extend remission duration and potentially reduce the need for later intensive treatments such as repeat chemotherapy or hematopoietic stem cell transplant.

How similar studies have performed: CD19‑directed CAR‑T therapies have produced high response rates in relapsed/refractory B‑ALL, but using CAR‑T as consolidation in newly diagnosed high‑risk patients is a newer strategy with limited prior data.

Eligibility criteria

Inclusion Criteria:

I. Patients of age .18 years with high-risk B-cell ALL in first remission and \<5% BM blasts with at least one high-risk feature defined as:

1. Ph-negative B-cell ALL:

   1. KMT2A rearranged ALL
   2. Complex cytogenetics as per NCCN 2022
   3. Low-hypodiploidy/tetraploidy
   4. Philadelphia-like ALL (based on CRLF2 overexpression or recurrent Ph-like genetic fusions)
   5. TP53 mutation (variant allele fraction \>2%)
   6. Persistent MRD by flow cytometry and/or NGS
2. Ph-positive B-cell ALL:

   1. IKZF1plus genotype (IKZF1 deletion coexisting with PAX5 or CDKN2A/2B, or PAR1 region deletions) or other high-risk features such as VPRB1 deletion, etc.
   2. High WBC (\>30 x 109/L) at initial presentation
   3. Persistent MRD by flow cytometry and/or NGS and/or PCR II. Performance status of 0, 1, or 2 III. Adequate organ function with creatinine less than or equal to 1.6 mg/dl, bilirubin less than or equal to 3.5 mg and ALT and AST less than or equal to 5 times institutional upper limit of normal IV. Patients should be CD19 expression positive (\>1%) before enrollment V. Patients with controlled CNS and/or other extramedullary leukemia will be eligible.

Exclusion Criteria:

1. Pregnant or lactating; women of child-bearing potential (WOCBP) must have negative pregnancy test. WOCBP defined as not post-menopausal for 12 months or no previous surgical sterilization.
2. Patients with history of Hepatitis B, Hepatitis C, Human Immunodeficiency Virus (HIV) infections, even if under control. (Patients with Hepatitis B core antibody positive alone will not be an exclusion factor if HBV DNA PCR is negative).
3. Active and uncontrolled disease/infection as judged by the treating physician
4. Unable or unwilling to sign the consent form

Where this trial is running

Houston, Texas

• The University of Texas M. D. Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Elias Jabbour, MD — M.D. Anderson Cancer Center
• Study coordinator: Elias Jabbour, MD

Conditions Acute Lymphocytic Leukemia