UCART22 Earns Orphan Drug Designation for Acute Lymphoblastic Leukemia in Europe


The European Commission granted orphan drug designation to UCART22 for acute lymphoblastic leukemia.

Mark Frattini, MD, PhD

Mark Frattini, MD, PhD

The European Commission (EC) has granted orphan drug designation to the allogeneic CD22-targeted CAR T-cell therapy UCART22 as a potential treatment option for patients with acute lymphoblastic leukemia (ALL).1

The CAR T-cell therapy is currently being investigated in the phase 1 BALLI-01 trial (NCT04150497) in patients with relapsed or refractory B-cell ALL (B-ALL).

“Patients with relapsed/refractory ALL have limited, if any, treatment options, especially for those who have failed prior CD19-directed CAR T-cell therapy and allogeneic stem cell transplant” Mark Frattini, MD, PhD, chief medical officer of Cellectis Biologics, stated in a news release. “The orphan drug designation for UCART22 marks an important step toward developing allogeneic CAR T products that would be readily available for all patients.”

Previous data from BALLI-01 presented at the 2023 ASH Annual Meeting showed that patients treated with dose level 2 of UCART22 process 2 (P2) at 1.0 x 106 cell/kg (n = 3) experienced an overall response rate (ORR) of 67%. Prior findings had shown that patients administered UCART22 process 1 (P1) at dose level 3 of 5.0 x 106 cells/kg (n = 6) achieved an ORR of 50%.2

Regarding the safety, no dose-limiting toxicities were reported in the 3 patients given UCART22 P2, and no instances of immune effector cell–associated neurotoxicity syndrome or graft-vs-host disease occurred. Cytokine release syndrome (CRS) occurred in 2 of 3 patients, including 1 patient who had grade 1 CRS that resolved without treatment, and another patient who had grade 2 CRS that resolved after treatment with tocilizumab (Actemra). One patient experienced grade 5 sepsis at day 40, which was classified as a serious adverse effect (AE) related to UCART22 and lymphodepletion.

The ongoing, phase 1, open-label, dose-escalation study is enrolling patients between 15 and 70 years of age with B-ALL who have a CD22 expression of at least 70%. At least 1 prior standard chemotherapy regimen and 1 salvage regimen are required for enrollment, and patients also need to have an ECOG performance status of 0 or 1.

UCART22 P1 was first evaluated at 1 x 105 cells/kg and 1 x 106 cells/kg following lymphodepletion consisting of 30 mg/m2 of fludarabine for 4 days plus 1 g/m2 of cyclophosphamide for 3 days. UCART22 P1 was then examined at 1 x 106 cells/kg, 2.5 x 106 cells/kg, and 5 x 106 cells/kg following lymphodepletion that included 30 mg/m2 of fludarabine, 0.5 g/m2 of cyclophosphamide, and 20 mg of alemtuzumab (Lemtrada) for 3 days each. UCART22 P2 is being evaluated at 1 x 106 cells/kg and 2.5 x 106 cells/kg after the same lymphodepletion regimen using fludarabine, cyclophosphamide, and alemtuzumab.

Safety, tolerability, and establishing the recommended phase 2 dose are the trial’s primary end points. Additional end points include investigator-assessed ORR; UCART22 expansion in peripheral blood and bone marrow; and immune reconstitution.

The 3 patients treated with UCART22 P2 included a female aged 17 years with Philadelphia chromosome (Ph)–negative B-ALL with a hypodiploid karyotype and a germline TP53 mutation who received prior treatment with multiagent chemotherapy, blinatumomab (Blincyto), inotuzumab ozogamicin (Besponsa), venetoclax (Venclexta), allogeneic stem cell transplant, and tisagenlecleucel (Kymriah). The second patient was a female aged 68 years with Ph-negative B-ALL with relapsed CD19-low disease after multiagent chemotherapy, blinatumomab, and inotuzumab ozogamicin. The third patient was male aged 27 years with B-ALL harboring an ABL2 fusion who received prior treatment with multiagent chemotherapy, blinatumomab, inotuzumab ozogamicin, TKIs, and an experimental autologous CD19-directed CAR T-cell therapy.

Additional any-grade AEs related to UCART22 reported in these 3 patients included asthenia (n = 1), chills (n = 1), pyrexia (n = 1), rash (n = 1), and hypotension (n = 1).

Additional data from BALLI-01 are expected to be reported by the end of 2024.1


  1. Cellectis receives orphan drug designation for UCART22, its allogeneic CAR T product for patients with acute lymphoblastic leukemia. News release. Cellectis Biologics. June 4, 2024. Accessed June 5, 2024.
  2. Jain N, Chevallier P, Liu H, et al. Updated results of the phase I BALLI-01 trial of UCART22 process 2 (P2), an anti-CD22 allogeneic CAR-T cell product manufactured by Cellectis Biologics, in patients with relapsed or refractory (R/R) CD22+ B-cell acute lymphoblastic leukemia (B-ALL). Blood. 2023;142(suppl 1):4847. doi:10.1182/blood-2023-187252
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