Immunotherapy using CAR T-cells for treating high-risk acute lymphoblastic leukaemia

Immunotherapy with CD19+CD22 CAR Redirected T-cells for High Risk/relapsed Paediatric CD19+ and CD22+ Acute Lymphoblastic Leukaemia

This study is testing a new type of immune therapy using specially modified T-cells to see if it can help children and young adults with high-risk leukemia feel better and stay in remission longer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: N/A to 24 Years
• Sex: All
• Sponsor: University College, London (Academic / other)
• Drugs / interventions: CAR T, chemotherapy, Chimeric Antigen Receptor
• Locations: 3 sites (London and 2 other locations)
• Trial ID: NCT02443831 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of CD19+CD22 Chimeric Antigen Receptor (CAR) T-cells in children and young adults with high-risk, relapsed acute lymphoblastic leukaemia. Participants will undergo leukapheresis to generate CAR T-cells, followed by lymphodepleting chemotherapy and total body irradiation before receiving the CAR T-cell infusion. The study aims to assess the duration of response and overall efficacy of this innovative immunotherapy approach in a vulnerable patient population.

Who should consider this trial

Good fit: Ideal candidates are children and young adults aged 24 years or younger with high-risk, relapsed CD19+ and CD22+ acute lymphoblastic leukaemia.

Not a fit: Patients with acute lymphoblastic leukaemia that does not express CD19 or CD22 may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could provide a new, effective option for children and young adults with high-risk relapsed acute lymphoblastic leukaemia.

How similar studies have performed: Other studies using CAR T-cell therapy for similar conditions have shown promising results, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Children and young adults (age 24 years or younger) with high risk/relapsed CD19+ and CD22+ acute lymphoblastic leukaemia with:

   1. Resistant disease (\>5% blasts) at end of ALLTogether-1 protocol or equivalent induction
   2. ALL with persisting high level MRD at 2nd time point of frontline national protocol (currently MRD \>10-4 at week 9 ALLTogether-1 Protocol or equivalent).
   3. High risk infant ALL (age \< 6 months at diagnosis with MLL gene rearrangement and either presenting white cell count \> 300 x 10\^9/L or poor steroid early response (i.e. circulating blast count \>1x10\^9/L following 7 day steroid pre-phase of induction as per national guidelines or equivalent)
   4. Any patient with t(17,19) TCF3-HLF rearrangement
   5. High risk 1st relapse (defined as very early (relapse within 18 months of diagnosis) and early relapses (any patient relapsing on therapy or within 6 months of completing treatment) and any relapse with high risk genetics, namely (KMT2A (MLL) rearrangements, low hypodiploidy/near haploidy, t(17;19)(q22;p13)/TCF3-HLF, iAMP21 and t(1;19)(q21;p13)/TCF3- PBX1, t(9;22)(34.1 q11.2)/BCR-ABL1
   6. Any on therapy relapse in patients age 16-24
   7. Any relapse of infant ALL
   8. ALL post ≥ 2nd relapse
   9. Any refractory relapse of ALL (defined as \> 1% blasts by flow cytometry after a at least 1 cycle of standard chemotherapy)
   10. ALL with MRD \>10-4 prior to planned stem cell transplant
   11. Any relapse of ALL eligible for stem cell transplant but no available HLA matched donor or other contraindication to transplant
   12. Any relapse of ALL after stem cell transplant as long as planned time of CD19+CD22CAR T cell infusion is \> 4 months post-transplant
   13. Early (defined as \< 6 months post-infusion) loss of B cell aplasia or any CD19+CD22+ relapse following CD19CAR T cell therapy with Tisagenlecleucel

   Note patients with isolated CNS relapse meeting one or more of the criteria above are eligible for the study
2. Agreement to have a pregnancy test, use adequate contraception (if applicable)
3. Written informed consent

Exclusion Criteria:

Exclusion Criteria for registration:

1. Active Hepatitis B, C or HIV infection
2. Oxygen saturation ≤ 90% on air
3. Bilirubin \> 3 x upper limit of normal
4. Creatinine \> 3 x upper limit of normal
5. Women who are pregnant or breastfeeding
6. Stem Cell Transplant patients only: active significant (overall Grade ≥ II, Seattle criteria) acute GVHD or moderate/ severe chronic GVHD (NIH consensus criteria) requiring systemic steroids.
7. Inability to tolerate leucapheresis
8. Karnofsky (age ≥ 10 years) or Lansky (age \< 10) score ≤ 50%
9. Pre-existing significant neurological disorder (other than CNS involvement of underlying haematological malignancy)
10. CD19 negative or CD22 negative disease

Exclusion criteria for CD19+CD22CAR T-cell infusion:

1. Severe intercurrent infection at the time of scheduled CD19+CD22 CAR T-cell infusion
2. Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19+CD22 CAR T-cell infusion
3. Allogeneic transplant recipients with active significant acute GVHD overall grade ≥II or moderate/severe chronic GVHD requiring systemic steroids at the time of scheduled CD19+CD22 CAR T-cell infusion. Note: Such patients will be excluded until the patient is GVHD free and off steroids

In addition, for CAR T infusion on D14: absence of CRS\>Gr2 or ICANS\>Gr2 after D0 CAR T infusion.

Where this trial is running

London and 2 other locations

• Great Ormond Street Hospital — London, United Kingdom (Recruiting)
• University College Hospital — London, United Kingdom (Recruiting)
• Manchester Royal Children's Hospital — Manchester, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Aniqa Tasnim

Conditions Acute Lymphoblastic Leukemia; high risk relapsed CD19+ and CD22+ acute lymphoblastic leukaemia