CARPALL: Immunotherapy With CD19+CD22 CAR T-cells for CD19+ and CD22+ Acute Lymphoblastic Leukaemia

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

This study aims to evaluate the safety, efficacy and duration of response of CD19+CD22 Chimeric Antigen Receptor (CAR) redirected autologous T-cells in children with high risk, relapsed CD19+ and CD22+ acute lymphoblastic leukaemia

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia
• Intervention / Treatment: Procedure: Leukapheresis; Radiation: Total Body Irradiation (TBI); Drug: Lymphodepletion with Fludarabine; Drug: Lymphodepletion with Cyclophosphamide; Biological: CD19+CD22 CAR T-cells

Detailed Description

This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product named CD19+CD22 Chimeric Antigen Receptor (CAR) T-cells (CD19+CD22 CAR T-cells) in children and young adults (age <24 years) with high risk, relapsed CD19+ and CD22+ acute lymphoblastic leukaemia. Following informed consent and registration to the trial, patients will undergo an unstimulated leukapheresis for the generation of the CD19+CD22 CAR T-cells. Patients will receive the CD19+CD22CAR T-cells following lymphodepleting chemotherapy and total body irradiation. The study will evaluate the safety, efficacy and duration of response of the CD19+CD22 CAR T-cells in children with high risk relapsed CD19+ and CD22+ acute lymphoblastic leukaemia.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Aniqa Tasnim; Phone Number: 0203 108 4753; Email: ctc.carpall@ucl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Great Ormond Street Hospital
    • Contact: Prof. Persis Amrolia
  • London, United Kingdom
    • Recruiting
    • University College Hospital
    • Contact: Dr Rachael Hough
  • Manchester, United Kingdom
    • Recruiting
    • Manchester Royal Children's Hospital
    • Contact: Dr Denise Bonney

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 24 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CD19+CD22 CAR T-cells; Patients meeting the eligibility criteria will have leukapheresis to isolate the blood immune cells used to manufacture the CD19+CD22CAR T-cells. Patients will receive lymphodepletion with low dose total body irradiation, fludarabine and cyclophosphamide prior to infusion of the CD19+CD22CAR T-cells.

Procedure: Leukapheresis; Patients will undergo an unstimulated leukapheresis to isolate the required immune cells to produce the CD19+CD22 CAR T-cells; Radiation: Total Body Irradiation (TBI); Participants will receive low-dose total body irradiation delivered as a single fraction on day -7 prior to CD19+CD22CAR T-cell infusion.; Drug: Lymphodepletion with Fludarabine; Patients will receive lymphodepleting chemotherapy with iv fludarabine on days -6 to -3 prior to CD19+CD22CAR T-cell infusion.; Drug: Lymphodepletion with Cyclophosphamide; Patients will receive lymphodepleting chemotherapy with iv cyclophosphamide on days -6 to -5 prior to CD19+CD22CAR T-cell infusion.; Biological: CD19+CD22 CAR T-cells; 1 dose of CD19+CD22 CAR T-cells given as an intravenous injection through a Hickman line or PICC line (peripherally inserted central catheter) on day 0.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular remission	Efficacy will be assessed by determining Minimal Residual Disease in the bone marrow aspirate using immunoglobulin heavy chain (IgH) quantitative polymerase chain reaction (qPCR) and/or Next Generation Sequencing in all patients. The proportion of patients achieving molecular remission at 28 days post CD19+CD22CAR T-cell infusion will be determined.	28 days
Incidence of unacceptable toxicity following CD19+CD22 CAR T-cell infusion	The incidence of unacceptable toxicity occurring within 28 days of CD19+CD22CAR T-cell infusion.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Generation of CD19+CD22 CAR T-cells	Evaluated by the number of therapeutic products generated.	Day 28
Molecular Remission	Efficacy will be assessed by determining Minimal Residual Disease in the bone marrow aspirate using immunoglobulin heavy chain (IgH) quantitative polymerase chain reaction (qPCR) and/or Next Generation Sequencing in all patients. The proportion of patients achieving molecular remission at 3 months post CD19+CD22CAR T-cell infusion will be determined.	3 months
Long-Term Molecular Remission	Number of patients in molecular remission without further therapy at 1 and 2 years	2 years
Duration of Response	Duration of response is measured from the time of achieving molecular remission or flow MRD negativity until the disease relapse or death, whichever occurs first.	15 years
Safety and Tolerability of the CAR T-cells	Incidence of adverse events and reactions (toxicity) to the CAR T-cells.	15 years
Incidence of B Aplasia	Incidence of B aplasia	2 years
Incidence of Hypogammaglobulinaemia	Incidence of hypogammaglobulinaemia	2 years
Frequency of Circulating CD19+CD22 CAR T-cells	Persistence and frequency of circulating CD19+CD22CAR T-cells in the peripheral blood by flow cytometry and qPCR analyses.	2 years
Relapse rate	Relapse rate	2 years
Overall Survival (OS)	Overall Survival (OS) at 1 and 2 years	2 years

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Study Chair: Persis Amrolia, UCL Institute of Child Health

Publications and helpful links

General Publications

• Ghorashian S, Kramer AM, Onuoha S, Wright G, Bartram J, Richardson R, Albon SJ, Casanovas-Company J, Castro F, Popova B, Villanueva K, Yeung J, Vetharoy W, Guvenel A, Wawrzyniecka PA, Mekkaoui L, Cheung GW, Pinner D, Chu J, Lucchini G, Silva J, Ciocarlie O, Lazareva A, Inglott S, Gilmour KC, Ahsan G, Ferrari M, Manzoor S, Champion K, Brooks T, Lopes A, Hackshaw A, Farzaneh F, Chiesa R, Rao K, Bonney D, Samarasinghe S, Goulden N, Vora A, Veys P, Hough R, Wynn R, Pule MA, Amrolia PJ. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nat Med. 2019 Sep;25(9):1408-1414. doi: 10.1038/s41591-019-0549-5. Epub 2019 Sep 2.
• Ghorashian S, Lucchini G, Richardson R, Nguyen K, Terris C, Guvenel A, Oporto-Espuelas M, Yeung J, Pinner D, Chu J, Williams L, Ko KY, Walding C, Watts K, Inglott S, Thomas R, Connor C, Adams S, Gravett E, Gilmour K, Lal A, Kunaseelan S, Popova B, Lopes A, Ngai Y, Hackshaw A, Kokalaki E, Carulla MB, Mullanfiroze K, Lazareva A, Pavasovic V, Rao A, Bartram J, Vora A, Chiesa R, Silva J, Rao K, Bonney D, Wynn R, Pule M, Hough R, Amrolia PJ. CD19/CD22 targeting with cotransduced CAR T cells to prevent antigen-negative relapse after CAR T-cell therapy for B-cell ALL. Blood. 2024 Jan 11;143(2):118-123. doi: 10.1182/blood.2023020621.
• Kokalaki E, Ma B, Ferrari M, Grothier T, Hazelton W, Manzoor S, Costu E, Taylor J, Bulek A, Srivastava S, Gannon I, Jha R, Gealy R, Stanczuk L, Rizou T, Robson M, El-Kholy M, Baldan V, Righi M, Sillibourne J, Thomas S, Onuoha S, Cordoba S, Pule M. Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR. Mol Ther. 2023 Jul 5;31(7):2089-2104. doi: 10.1016/j.ymthe.2023.03.020. Epub 2023 Mar 21.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2041

Study Registration Dates

• First Submitted: April 29, 2015
• First Submitted That Met QC Criteria: May 13, 2015
• First Posted (Estimated): May 14, 2015

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: high risk relapsed CD19+ and CD22+ acute lymphoblastic leukaemia
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Organic Chemicals; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Cytological Techniques; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Biological Therapy; Cytapheresis; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cyclophosphamide; fludarabine; Leukapheresis; Whole-Body Irradiation
• Other Study ID Numbers: UCL 14/0529

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No