UCART22 for Acute Lymphoblastic Leukemia

Recruiting at 16 trial locations

Overseen By Cellectis Central Contact

Age: Any Age

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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a first-in-human, open-label, dose escalation and expansion study of UCART22 administered intravenously to patients with relapsed or refractory B-cell acute Lymphoblastic Leukemia (B-ALL). The purpose of this study is to evaluate the safety and clinical activity of UCART22 and determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

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.

What data supports the effectiveness of the treatment UCART22 for Acute Lymphoblastic Leukemia?

Research on similar treatments, like anti-CD22 CAR T-cell therapy, shows it can lead to remissions in patients with relapsed acute lymphoblastic leukemia, suggesting UCART22 might also be effective. ^{1 2 3 4 5}

What makes the treatment UCART22 unique for acute lymphoblastic leukemia?

UCART22 is unique because it targets the CD22 antigen on B-cells, offering an alternative for patients who do not respond to or relapse after CD19-targeted therapies. This approach uses engineered T-cells to specifically attack leukemia cells, which is different from traditional chemotherapy or bone marrow transplants. ^{1 2 3 6 7}

Research Team

Nitin Jain, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States 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. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Importance of long-term follow-up in evaluating treatment regimens for adults with acute lymphoblastic leukemia. [2019]

4. United States 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Novel antibody therapy in acute lymphoblastic leukemia. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Characterization of CD22 expression in acute lymphoblastic leukemia. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia. [2020]