This phase II trial tests how well consolidation therapy with obecabtagene autoleucel works to control disease in patients with newly diagnosed, high-risk B-cell acute lymphoblastic leukemia (ALL). Consolidation therapy is treatment given after initial therapy to kill any remaining cancer cells. Obecabtagene autoleucel is a type of chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a treatment in which a patient's T-cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T-cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added to the T-cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T-cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Chemotherapy drugs such as fludarabine and cyclophosphamide are given before CAR T-cell infusions to prepare the body to receive the CAR T-cells. Obecabtagene autoleucel is approved for the treatment of B-cell ALL that has come back after a period of improvement or that does not respond to treatment, but it is not approved as a consolidation therapy. It may be an effective consolidation treatment option for patients with newly diagnosed, high risk B-cell ALL.
Additional locations may be listed on ClinicalTrials.gov for NCT07053059.
Locations matching your search criteria
United States
Texas
Houston
M D Anderson Cancer CenterStatus: Active
Contact: Elias Jabbour
Phone: 713-792-4764
PRIMARY OBJECTIVE:
I. To assess the efficacy of obecabtagene autoleucel (anti-CD19 autologous derived chimeric antigen receptor T-cell [CAR-T]) in terms of event-free survival (EFS) in patients with newly diagnosed high-risk B-cell ALL (defined by baseline high-risk genomics or persistent measurable residual disease [MRD]) post cytoreductive chemoimmunotherapy: 18-month EFS.
SECONDARY OBJECTIVES:
I. 24-month overall survival (OS).
II. Rate of persistent MRD negativity by flow cytometry and next generation sequencing (NGS) at 18 months. (For Philadelphia [Ph]-negative B-cell ALL)
III. Rate of persistent MRD negativity by flow cytometry, NGS and BCR::ABL1 real time polymerase chain reaction (qPCR) (complete molecular response [CMR]) at 18 months. (For Ph-positive B-cell ALL)
IV. Achievement of BCR::ABL1 complete molecular response (CMR) in patients with Ph-positive ALL having persistent measurable disease at any level before obecabtagene autoleucel (obe-cel) infusion.
V. Achievement of NGS MRD negativity amongst patients in complete remission (CR) and not MRD negative before obe-cel.
VI. Time to initiation of next anti-leukemia therapy except hematopoietic stem cell transplantation (HSCT) when done in ongoing continued morphological response (patients who did not start next anti-leukemia therapy except HSCT will be censored at the last follow-up/death).
VII. Rates of HSCT in morphologic remission after obe-cel infusion.
VIII. Safety.
EXPLORATORY OBJECTIVES:
I. CAR-T-cell expansion by digital droplet polymerase chain reaction (PCR) (ddPCR) assay by a manufacturer designated central laboratory (CellCarta) on days 7, 14, 21, 28, 3 months and then every 3 months up to 12 months post infusion.
II. B-cell aplasia (days 0, 7, 14, 28, monthly up to 3 months and then every 3 months up to 24 months post infusion).
III. Measurable residual disease (MRD) negativity by next-generation sequencing (NGS) (at 1 in 10^5-6 sensitivity) (peripheral blood [PB] on day [D]14 and PB/bone marrow [BM]: day 28, and then once every 3 months [Q3 months] up to 24 months post infusion).
IV. Cytokine panel to study cytokine profile including interluekin-1 (IL1), interluekin-6 (IL6), interferon gamma (IFNG), tumor necrosis factor alpha (TNFalpha) from infusion (days 0, 1, 2, 4, 7, 10, 14, 28).
V. Additional correlatives samples to address tumor samples and immune system factors will be collected at baseline, D28 and Q3 months from infusion.
OUTLINE:
Patients undergo leukapheresis for production of the obecabtagene autoleucel product on study. Patients receive fludarabine intravenously (IV) over 30 minutes on days -6 to -3, and receive cyclophosphamide IV over 30 minutes on days -6 and -5. Patients then receive obecabtagene autoleucel IV on days 1 and 10. Patients also undergo bone marrow aspiration and/or biopsy and collection of blood samples throughout the study and undergo computed tomography (CT)/positron emission tomography (PET)-CT during follow up. Patients may undergo multigated acquisition scan (MUGA) or echocardiography (ECHO) and liver ultrasound or elastography before treatment.
After completion of study treatment, patients are followed up on days 14 and 28, every 3 months for 12 months, every 6 months for 2 years, and then annually for 2 years.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorElias Jabbour
