UCART22 for Acute Lymphoblastic Leukemia

Recruiting at 18 trial locations

Overseen By Cellectis Central Contact

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Cellectis S.A.

Disqualifiers: Prior cellular therapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called UCART22, a type of cell therapy, for individuals with B-cell acute lymphoblastic leukemia (B-ALL). The goal is to identify a safe and effective dose of UCART22 for patients whose cancer has returned or hasn't responded to other treatments. Participants will receive varying doses to determine the best one for further research. Candidates may qualify if they have B-ALL that didn't respond to at least two different treatments and their cancer cells show a specific marker called CD22. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot have had prior cellular or gene therapy within 60 days before joining the trial.

Is there any evidence suggesting that UCART22 is likely to be safe for humans?

Research has shown that UCART22, a treatment tested for B-cell acute lymphoblastic leukemia (B-ALL), has generally been well-tolerated in earlier studies. Initial results from previous patients indicated that UCART22 did not cause serious side effects for most individuals. Some patients experienced a decrease in cancer cells, and the treatment's safety was considered good. This suggests that UCART22 could be a safe option for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Acute Lymphoblastic Leukemia, which often include chemotherapy and targeted therapies, UCART22 is a cutting-edge approach leveraging CAR-T cell technology. UCART22 is unique because it's an "off-the-shelf" CAR-T therapy, meaning it's engineered from healthy donor cells rather than the patient's own cells, which can significantly reduce the time to treatment. This therapy specifically targets the CD22 protein on leukemia cells, which could offer more precise and effective targeting of cancer cells with potentially fewer side effects. Researchers are excited about UCART22 because it represents a new frontier in personalized cancer treatment, offering hope for improved outcomes in patients who may not respond to existing therapies.

What evidence suggests that UCART22 might be an effective treatment for acute lymphoblastic leukemia?

Research has shown that UCART22, the investigational treatment in this trial, may help treat B-cell acute lymphoblastic leukemia (B-ALL) that has returned or is difficult to treat. Studies found that UCART22 was generally safe for patients, as it did not cause serious side effects. In some cases, it significantly reduced cancer cells, and some patients even achieved complete remission. Specifically, one study reported that about 67% of patients responded positively to the treatment, with one patient remaining cancer-free for over 84 days. These early results suggest UCART22 could be a promising option for people with challenging cases of B-ALL. ^{1 2 3 4 6}

Who Is on the Research Team?

Nitin Jain, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for people with B-cell acute lymphoblastic leukemia (B-ALL) that has come back or didn't respond to treatment. They must have tried at least one standard chemo and one more intense rescue therapy. Patients who've had cell or gene therapies in the last 60 days can't join.

Inclusion Criteria

My leukemia cells test positive for CD22.

I have undergone at least one initial and one follow-up chemotherapy treatment.

I have relapsed or refractory B-cell acute lymphoblastic leukemia.

Exclusion Criteria

I haven't had any cell or gene therapy in the last 60 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Several tested doses of UCART22 until the Maximum Tolerated Dose (MTD) is identified and establish Recommended Phase 2 Dose (RP2D)

Variable duration until MTD is identified

Dose Expansion

UCART22 administered at the RP2D

Variable duration

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• UCART22

Trial Overview The study tests UCART22, a new therapy given through the veins, on patients with relapsed/refractory B-ALL. It aims to find out how safe it is, its effects on leukemia, and the best dose for future studies.

How Is the Trial Designed?

Group I: Dose Escalation Experimental Treatment 2 Interventions

Several tested doses of UCART22 until the Maximum Tolerated Dose (MTD) is identified and establish Recommended Phase 2 Dose (RP2D) Dose Expansion: UCART22 administered at the RP2D

UCART22 is already approved in European Union, United States for the following indications:

Approved in European Union as UCART22 for:

• Acute Lymphoblastic Leukemia (ALL)

Approved in United States as UCART22 for:

• Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL)

Who Is Running the Clinical Trial?

Cellectis S.A.

Lead Sponsor

Trials

6

Recruited

200+

Published Research Related to This Trial

In a multicenter trial involving 525 children with relapsed acute lymphoblastic leukemia (ALL), over one-third achieved long-term remission, indicating that the treatment strategies were effective for a significant portion of patients.

Patients in high-risk groups who underwent stem-cell transplantation (SCT) had better event-free survival rates compared to those who received chemotherapy alone, highlighting the importance of SCT for improving outcomes in these high-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90. Tallen, G., Ratei, R., Mann, G., et al.[2022]

A first-in-human trial of anti-CD22 CAR T-cell therapy in children and young adults with relapsed acute lymphocytic leukemia demonstrated that the treatment is feasible, safe, and effective, resulting in remissions for most patients.

The study found that infusing higher numbers of T cells was associated with better treatment responses, suggesting a dose-dependent effect in the therapy's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD22 CAR Therapy Leads to ALL Remissions. [2018]

In a study involving 58 children and young adults with relapsed or refractory B-cell malignancies, CD22-targeted CAR T cells achieved a complete remission rate of 70%, demonstrating significant efficacy as an alternative treatment for patients who did not respond to CD19-targeted therapies.

The treatment was generally safe, with most side effects being mild to moderate, although cytokine release syndrome occurred in 86.2% of participants, indicating the need for careful monitoring and potential toxicity management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD4/CD8 T-Cell Selection Affects Chimeric Antigen Receptor (CAR) T-Cell Potency and Toxicity: Updated Results From a Phase I Anti-CD22 CAR T-Cell Trial. Shah, NN., Highfill, SL., Shalabi, H., et al.[2021]

Pediatric-based chemotherapy regimens for treating adult acute lymphoblastic leukemia (ALL) have shown improved outcomes in young adults up to 45 years old compared to traditional adult therapies.

Emerging therapies, including monoclonal antibodies like rituximab and epratuzumab, as well as CAR therapy and Blinatumomab, are being studied in clinical trials and may enhance treatment response while reducing toxicity in ALL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel antibody therapy in acute lymphoblastic leukemia. Kochuparambil, ST., Litzow, MR.[2021]

In a study of 163 children and young adults with relapsed and chemotherapy-refractory B-precursor ALL, CD22 was found to be expressed on at least 90% of leukemia cells, making it a promising target for therapy.

However, patients with 11q23 (MLL) rearrangement showed lower CD22 expression and some had CD22-negative cells, indicating that these cases may need special attention when considering anti-CD22 treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of CD22 expression in acute lymphoblastic leukemia. Shah, NN., Stevenson, MS., Yuan, CM., et al.[2019]

Over 20 years, 250 adults with acute lymphoblastic leukemia (ALL) were treated with various multidrug protocols, with the L10 and L10M protocols showing the highest long-term remission rates of 52% and 40%, respectively, compared to more recent protocols.

The overall long-term survival rate was 31%, with 35% of patients achieving complete remission remaining relapse-free for over 5 years, indicating that early remission is crucial for improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Importance of long-term follow-up in evaluating treatment regimens for adults with acute lymphoblastic leukemia. Clarkson, B., Gaynor, J., Little, C., et al.[2019]

Targeted therapies, including monoclonal antibodies, have significantly improved survival rates for patients with chronic and acute lymphoblastic leukemia, showcasing the effectiveness of these modern treatment approaches.

Monoclonal antibodies targeting CD20 and CD22 receptors have shown promising results in preclinical studies and are advancing into clinical trials, with some already receiving FDA approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia. Jacob, JA., Salmani, JM., Chen, B.[2020]

Citations

1. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4847/504776/Updated-Results-of-the-Phase-I-BALLI-01-Trial-of

Updated Results of the Phase I BALLI-01 Trial of UCART22 ... Preliminary results from patients treated with UCART22 manufactured by a CMO (Process 1 (P1)) showed that UCART22 was well-tolerated and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10430638/

UPDATED RESULTS OF THE PHASE I BALLI-01 TRIAL ... Preliminary results from the BALLI-01 study (NCT04150497) showed that UCART22 was well tolerated, and blast reductions were achieved.

3. cellectis.com cellectis.com/uploads/files/P1408_Nicolas_Boissel_Mark_Frattini__EHA_2023-UCART22_Final_poster17May23.pdf

Updated Results of the Phase I BALLI-01 Trial of UCART22 ... ➢As of 31 December 2021, 19 patients were treated in 6 cohorts: FC-DL1 (n=3); FC-DL2 (n=2); FCA-DL2. (n=3); FCA-DL2i (n=4); and FCA-DL3 ( n=6). Note that 1 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123114480

Updated Results of the Phase I BALLI-01 Trial of UCART22 ... For UCART22 P2, FCA-DL2, 2/3 pts (67%) responded: Pt 2 achieved an MRD neg CR lasting over 84 days after UCART22 infusion; Pt 1 achieved an MRD negative MLFS up ...

5. withpower.com withpower.com/trial/phase-1-precursor-cell-lymphoblastic-leukemia-lymphoma-9-2019-e8c88

UCART22 for Acute Lymphoblastic Leukemia In a study involving 58 children and young adults with relapsed or refractory B-cell malignancies, CD22-targeted CAR T cells achieved a complete remission rate ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04150497?term=AREA%5BSponsorSearch%5D(COVERAGE%5BFullMatch%5DEXPANSION%5BNone%5D(%22Cellectis%20S.A.%22))&rank=2

Phase 1/2 Study of UCART22 in Patients With Relapsed or ... Investigator assessed overall response rate according to the Response criteria for Acute Lymphoblastic Leukemia (ALL), At Day 28, Day 56, Day 84, Month 3, Month ...