A Phase 1/2a Study of UCART22 in B-cell Acute Lymphoblastic Leukemia (BALLI-01)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cellectis

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 Nov 2025 → ongoing

Decision date (initial)

2023-07-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2022-502305-15-00

EudraCT number

2020-004768-24

ClinicalTrials.gov

NCT04150497

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

For the Dose-escalation:
-To assess the safety and tolerability of UCART22 and determine the Maximum Tolerated Dose (MTD) and/or
Recommended Phase 2 Dose (RP2D) of UCART22 in patients with R/R BALL.

For the Dose-Expansion:
-To confirm the MTD and/or RP2D in patients with R/R B-ALL who have
failed a CD19 directed therapy.

Secondary objectives 11

1. Dose Escalation:To assess the anti-leukemic activity of UCART22 in patients with R/R BALL
2. Dose Escalation:To identify the optimal lymphodepletion regimen to evaluate with UCART22 RP2D in Dose Expansion portion
3. Dose Escalation:To measure the development of a potential immune response to alemtuzumab
4. Dose Escalation:To determine the PK profile/exposure levels of alemtuzumab
5. Dose Escalation:To determine the pharmacodynamics (PD) of alemtuzumab
6. Dose Expansion:To assess the antileukemic activity of UCART22 in R/R B-ALL subjects who have failed a CD19 directed therapy
7. Dose Expansion:To assess MRD negativity by an approved genomic assay in a central laboratory
8. Dose Expansion:To assess the safety and tolerability of UCART22 in R/R B-ALL subjects who have failed a CD19 directed therapy
9. Dose Expansion:To measure the development of an immune response to alemtuzumab
10. Dose Expansion:To determine the PK profile/exposure levels of alemtuzumab
11. Dose expansion: To determine the pharmacodynamics (PD) of alemtuzumab

Conditions and MedDRA coding

Relapsed or refractory B-cell Acute Lymphoblastic Leukemia

Regulatory references

Scientific advice from competent authorities

EMA Regulatory Submissions Expediter Limited, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age: a.Dose Escalation phase: Patient aged ≥15 years and ≤70 years; b.Dose Expansion phase: Patient aged ≥12 and ≤70 years
2. Diagnosis and Prior Therapy: a.Dose Escalation phase: Diagnosed with R/R B-ALL; prior therapy must include at least one standard chemotherapy regimen and at least one salvage regimen. There must be no available alternative curative therapies and patients must be ineligible for allogeneic hematopoietic stem cell transplantation (HSCT), have refused HSCT, recurred after HSCT, or have active disease that prohibits HSCT at the time of enrollment. b.Dose Expansion phase: Diagnosed with R/R B-ALL; prior therapy must include at least one standard chemotherapy regimen and at least one salvage regimen, and must have included a CD19 targeted treatment. There must be no available alternative curative therapies and patients must be ineligible for allogeneic hematopoietic stem cell transplantation (HSCT), have refused HSCT, recurred after HSCT, or have active disease that prohibits HSCT at the time of enrollment
3. Disease burden: a.Dose Escalation phase: Patients must have measurable or evaluable disease in the bone marrow of at least 0.01% blasts or non-CNS extramedullary disease at the time of enrollment; b.Dose Expansion phase: Patients must have measurable or evaluable disease in the bone marrow of at least 5% blasts at the time of enrollment
4. CD22 Expression: a.Dose escalation phase: At least 70% of B-ALL blast cells expressing CD22 by flow cytometry performed as per standard practice; b.Dose expansion phase: At least 70% of B-ALL blast cells must express CD22 by flow cytometry performed as per standard practice
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 for subjects ≥ 18 years; Lansky/Karnofsky score ≥ 70 for subjects < 18 years
6. Adequate organ function, including renal and hepatic function based on the last assessment performed within the Screening Period, defined as: i)Creatinine clearance ≥60 mL/min (assessed as glomerular filtration rate using the Cockcroft-Gault formula); ii)Alanine aminotransferase and aspartate aminotransferase 3×upper limit of normal (ULN) or ≤5×ULN if deemed to be elevated due to leukemic involvement; iii)Total bilirubin 2×ULN or ≤3×ULN if deemed to be elevated due to leukemic involvement; iv)Left ventricular ejection fraction ≥50%
7. Women of childbearing potential must have a negative, highly sensitive serum pregnancy test performed within 7 days prior to enrollment

Exclusion criteria 24

1. Prior CAR T cellular therapy or investigational cellular therapy within 60 days prior to enrollment
2. Prior CD22 directed CAR T cell therapy
3. Prior monoclonal antibody therapy within 30 days prior to enrollment
4. Use of other investigational products within 5 half-lives or within 14 days prior to enrollment, whichever is longer
5. Use of systemic chemotherapy within 14 days prior to enrollment (except 6 weeks for nitrosoureas)
6. Use of rituximab, other anti-CD20 antibodies known to have the same epitope as rituximab, or anti-CD20 antibodies for which the epitope is unknown within 3 months prior to enrollment
7. Planned treatment with > 20 mg of prednisone or equivalent between Days -7 and +28 of UCART22 infusion
8. Burkitt cell leukemia
9. More than 1 allogeneic HSCT received
10. Allogeneic HSCT within 90 days prior to enrollment
11. Donor lymphocyte infusion within 6 weeks prior to enrollment
12. Active, acute or chronic graft-versus-host disease (GvHD). Patients should be off all immunosuppression for 6 weeks prior to enrollment
13. Radioimmunotherapy or radiotherapy within 8 weeks
14. Hyperleukocytosis (≥10,000 blasts/μL) or rapidly progressive disease
15. Patients with radiologically-detected CNS leukemia or CNS-3 disease
16. Presence of an active and clinically relevant CNS disorder
17. Isolated extramedullary relapse (i.e., testicular, CNS)
18. Known infection with human immunodeficiency virus or human T-cell leukemia/lymphoma virus type 1 or active hepatitis B or active hepatitis C
19. Any known uncontrolled cardiovascular disease in the previous 6 months before enrollment
20. History of severe recurrent viral infections or active bacterial, fungal, or viral infection not controlled by adequate treatment at enrollment
21. Abnormal findings and/or clinically significant Grade ≥3 non hematological toxicity that might jeopardize the patient's safety
22. Evidence of another uncontrolled malignancy within 2 years prior to Screening
23. Active macrophage activation syndrome (MAS)
24. For a patient intended to receive alemtuzumab as part of their lymphodepletion regimen (Arm FCA): i)History of hypersensitivity to alemtuzumab; or ii)Inability for any reason to receive appropriate anti-infective prophylaxis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Dose escalation Phase: Incidence, nature and severity of adverse events and serious adverse events (SAEs); Incidence, nature, and severity of adverse events and SAEs associated with lymphodepletion
2. Dose Escalation phase: Proportion of patients in each dose level cohort with dose-limiting toxicity during the DLT observation period
3. Dose expansion phase: Incidence, nature and severity of adverse events and serious adverse events (SAEs); Incidence, nature, and severity of adverse events and SAEs associated with lymphodepletion

Secondary endpoints 16

1. Dose Escalation phase: Investigator assessed overall response rate (ORR) [complete response + complete response CR with incomplete hematologic recovery +complete response with partial hematologic recovery [CR+CRi+ CRh]) according to the Response criteria for Acute Lymphoblastic Leukemia (ALL) and Investigator assessed rate of MRD negativity defined as (BM ALL blasts <0.01%) by flow cytometry
2. Dose Escalation phase: Investigator assessed rate of minimal residual disease (MRD) negativity (defined as bone marrow (BM) ALL blasts < 0.01%) by flow cytometry
3. Dose Escalation phase: Time to Event Endpoints: Progression free survival (PFS); overall survival (OS) and duration of response (DoR)
4. Dose Escalation phase: Proportion of patients who achieve adequate response and proceed to hematopoietic stem cell transplant (HSCT)
5. Dose Escalation phase: Incidence, nature, and severity of adverse events and SAEs associated with lymphodepletion, associated anti-leukemic activity and corresponding host T-cell recovery and CAR+ T-cell expansion
6. Dose Escalation phase: Monitoring of anti-CD52 (alemtuzumab) antibodies in serum pre- and post-administration of alemtuzumab
7. Dose Escalation phase: Quantitation of alemtuzumab levels in serum post administration
8. Dose Escalation phase: Quantitation of T, B, and NK cells and total lymphocytes in periperal blood post administration
9. Dose Expansion Phase: Investigator assessed ORR (CR+CRi+CRh) according to the Response criteria for ALL
10. Dose Expansion Phase:Time to Event Endpoints: Progression free survival (PFS); overall survival (OS) and duration of response (DoR)
11. Dose Expansion phase: Proportion of subjects who achieve adequate response and proceed to hematopoietic stem cell transplant (HSCT) without additional antileukemia therapy
12. Dose Expansion phase: MRD negative rate measured on BM by ClonoSeq MRD assay at central laboratory
13. Dose Expansion phase:Incidence, nature and severity of adverse events and serious adverse events (SAEs) during the Dose Expansion phase
14. Dose Expansion phase: Monitoring of anti-CD52 (alemtuzumab) antibodies in serum pre- and post-administration of alemtuzumab)
15. Dose Expansion phase: Quantitation of alemtuzumab levels in serum post administration
16. Dose Expansion phase: Quantitation of T, B, and NK cells and total lymphocytes in periperal blood post administration

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cellectis

Sponsor organisation

Cellectis

Address

8 Rue De La Croix Jarry

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Cellectis

Contact name

clinical trial information desk

Public contact point

Organisation

Cellectis

Contact name

clinical trial information desk

Third parties 8

Locations

3 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 28 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications