CD19 CAR-T Cell Therapy in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia: A Phase I/II Study

Browse trials for

• Recurrence 4,347
• Burkitt Lymphoma 407
• Precursor Cell Lymphoblastic Leukemia-Lymphoma 2,121

Keywords

• CAR-T
• Acute lymphoblastic leukemia

Recurrence

4,347 studies on the registry are indexed under Recurrence; 1,004 are open to participants now.

This study's planned enrollment of 30 is below the median of 50 across 3,429 interventional studies indexed under Recurrence.

Lead sponsor

Hospital Universitario Dr. Jose E. Gonzalez is the lead sponsor of 83 studies on the registry; 12 are open to participants now.

Study arms

• Experimental
  High disease burden (≥5% bone marrow blasts)

  Patients with ≥5% blasts in bone marrow at the time of lymphodepletion receive a single infusion of MB-CART19.1, with the cell dose assigned by dose level according to a 3+3 dose-escalation design: De-escalation Level 1x10\^5 CAR-positive cells/kg; Dose Level 1 (starting dose) 5x10\^5; Dose Level 2, 1x10\^6; Dose Level 3, 2x10\^6.

  Biological: MB-CART19.1

• Experimental
  Low disease burden (<5% bone marrow blasts)

  Patients with \<5% blasts in bone marrow at the time of lymphodepletion receive a single infusion of MB-CART19.1, with the cell dose assigned by dose level according to a 3+3 dose-escalation design: De-escalation Level, 5x10\^5 CAR-positive cells/kg; Dose Level 1 (starting dose), 1x10\^6; Dose Level 2, 2x10\^6; Dose Level 3, 5x10\^6.

  Biological: MB-CART19.1

Interventions

• BiologicalMB-CART19.1

  MB-CART19.1 are autologous T cells genetically modified to express a chimeric antigen receptor (CAR) targeting CD19.

Primary outcomes

1. Incidence of dose-limiting toxicities (DLTs) and determination of the recommended Phase II dose (RP2D)

   Safety and tolerability of MB-CART19.1 assessed by the incidence of dose-limiting toxicities (DLTs), defined as grade \>=3 adverse events considered related to MB-CART19.1 or the lymphodepletion regimen occurring within 30 days after infusion. The RP2D is defined as the maximum tolerated dose (MTD), or the highest dose level studied if the MTD is not reached, using a 3+3 dose-escalation design.

   Time frame: 30 days post-infusion

2. Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)

   Overall safety of MB-CART19.1 assessed by the frequency and severity of treatment-emergent AEs and SAEs.

   Time frame: Up to 24 months post-infusion

Secondary outcomes

1. Overall response rate (ORR)

   Proportion of patients achieving an overall response, defined as complete remission (CR) plus complete remission with incomplete hematologic recovery (CRi), assessed by bone marrow morphology and flow cytometry.

   Time frame: Day 30 and Day 100 post-infusion

2. Complete remission rate with negative measurable residual disease (MRD)

   Proportion of patients achieving complete remission with negative MRD, defined as \<0.001% residual leukemic cells in bone marrow by multiparameter flow cytometry.

   Time frame: Day 30 and Day 100 post-infusion

3. Overall survival (OS)

   Time from study entry to death from any cause.

   Time frame: Up to 24 months post-infusion

4. Event-free survival (EFS)

   Time from MB-CART19.1 infusion to the first of the following events: absence of response, disease progression, relapse after achieving CR or CRi, or death from any cause.

   Time frame: Up to 24 months post-infusion

5. Leukemia-free survival (LFS)

   Time from documentation of complete remission to disease relapse or death related to the disease, whichever occurs first.

   Time frame: Up to 24 months post-infusion

Publications

• Ghobadi A, Caimi PF, Reese JS, Goparaju K, di Trani M, Ritchey J, Jackson Z, Tomlinson B, Schiavone JM, Kleinsorge-Block S, Zamborsky K, Eissenberg L, Schneider D, Boughan KM, Zabor EC, Metheny L, Gallogly M, Kruger W, Kadan M, Worden A S A, Sharma A, Cooper BW, Otegbeye F, Sekaly RP, Wald DN, Carlo-Stella C, DiPersio J, Orentas R, Dropulic B, de Lima M. Treatment of non-Hodgkin lymphoma with point-of-care manufactured CAR T cells: a dual institution, phase 1 trial. EClinicalMedicine. 2025 Mar 4;81:103138. doi: 10.1016/j.eclinm.2025.103138. eCollection 2025 Mar. PubMed 40115173 ↗
• Muller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Volkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schafer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Kronke G, Mackensen A, Schett G. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med. 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917. PubMed 38381673 ↗
• Mackensen A, Hanssens L, Stelljes M, Bethge WA, Feuchtinger T, Kunkele A, et al. A Phase I Open Label Dose Escalation Study of MB-CART19.1 in Relapsed and Refractory CD19+ B Cell Malignancies, Interim Preliminary Results in Pediatric ALL, Adult ALL Including CLL Cohorts. Blood. 2021;138(Supplement 1):3836. doi:10.1182/blood-2021-152452.

Individual participant data

Plan to share: Yes — De-identified individual participant data (IPD) underlying the results reported in this study will be made available to qualified external researchers. The data to be shared will include individual participant-level data for all pre-specified primary and secondary outcome measures, after de-identification. Requests will be granted after review by the Research Ethics Committee of the Hospital Universitario "Dr. Jose Eleuterio Gonzalez". Data will be provided following the execution of a data sharing/transfer agreement and in accordance with applicable Mexican personal data protection laws.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form