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

NCT02443831 | Recruiting Phase 1 DMC

• 1 other identifier: UCL 14/0529
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Acute Lymphoblastic Leukemia

Keywords

high risk relapsed CD19+ and CD22+ acute lymphoblastic leukaemia

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicity (DLT) following CD19+CD22 CAR T-cell infusion

  The incidence of dose limiting toxicity (DLT) occurring within 28 days of CD19+CD22CAR T-cell infusion.

  28 days

• 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

Secondary Outcomes (10)

• Feasibility of Generation of CD19+CD22 CAR T-cells

  Day 28

• Molecular Remission

  3 months

• Long-Term Molecular Remission

  2 years

• Duration of Response

  15 years

• Safety and Tolerability of the CAR T-cells

  15 years

Study Arms (1)

CD19+CD22 CAR T-cells

EXPERIMENTAL

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; Radiation: Total Body Irradiation (TBI); Drug: Lymphodepletion with Fludarabine; Drug: Lymphodepletion with Cyclophosphamide; Biological: CD19+CD22 CAR T-cells

Interventions

Leukapheresis PROCEDURE

Patients will undergo an unstimulated leukapheresis to isolate the required immune cells to produce the CD19+CD22 CAR T-cells

CD19+CD22 CAR T-cells

Total Body Irradiation (TBI) RADIATION

Participants will receive total body irradiation delivered as a single fraction (2Gy) on day -7 prior to CD19+CD22CAR T-cell infusion.

CD19+CD22 CAR T-cells

Lymphodepletion with Fludarabine DRUG

Patients will receive lymphodepleting chemotherapy with iv fludarabine 30 mg/m2 on days -6 to -3 prior to CD19+CD22CAR T-cell infusion.

CD19+CD22 CAR T-cells

Lymphodepletion with Cyclophosphamide DRUG

Patients will receive lymphodepleting chemotherapy with iv cyclophosphamide 0.5 g/m2 on days -6 to -5 prior to CD19+CD22CAR T-cell infusion.

CD19+CD22 CAR T-cells

CD19+CD22 CAR T-cells BIOLOGICAL

Dose level 1: 2 doses of 4 x 10\^5 CD19+CD22 CAR T-cells/kg Dose level 2: 2 doses of 1 x 10\^6 CD19+CD22 CAR T-cells/kg given as a split dose as an intravenous injection through a Hickman line or PICC line (peripherally inserted central catheter) on day 0 and day 14.

CD19+CD22 CAR T-cells

Eligibility Criteria

• Age: Up to 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children and young adults (age 24 years or younger) with high risk/relapsed CD19+ and CD22+ acute lymphoblastic leukaemia with:
• Resistant disease (\>5% blasts) at end of ALLTogether-1 protocol or equivalent induction
• 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).
• 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)
• Any patient with t(17,19) TCF3-HLF rearrangement
• 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
• Any on therapy relapse in patients age 16-24
• Any relapse of infant ALL
• ALL post ≥ 2nd relapse
• Any refractory relapse of ALL (defined as \> 1% blasts by flow cytometry after a at least 1 cycle of standard chemotherapy)
• ALL with MRD \>10-4 prior to planned stem cell transplant
• Any relapse of ALL eligible for stem cell transplant but no available HLA matched donor or other contraindication to transplant
• Any relapse of ALL after stem cell transplant as long as planned time of CD19+CD22CAR T cell infusion is \> 4 months post-transplant
• 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

You may not qualify if:

• Active Hepatitis B, C or HIV infection
• Oxygen saturation ≤ 90% on air
• Bilirubin \> 3 x upper limit of normal
• Creatinine \> 3 x upper limit of normal
• Women who are pregnant or breastfeeding
• 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.
• Inability to tolerate leucapheresis
• Karnofsky (age ≥ 10 years) or Lansky (age \< 10) score ≤ 50%
• Pre-existing significant neurological disorder (other than CNS involvement of underlying haematological malignancy)
• CD19 negative or CD22 negative disease
• Severe intercurrent infection at the time of scheduled CD19+CD22 CAR T-cell infusion
• Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19+CD22 CAR T-cell infusion
• 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.

Sponsors & Collaborators

• University College, London: lead

Study Sites (3)

Great Ormond Street Hospital

London, United Kingdom

RECRUITING

University College Hospital

London, United Kingdom

RECRUITING

Manchester Royal Children's Hospital

Manchester, United Kingdom

RECRUITING

Related Publications (3)

• 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.

  PMID: 37647647 DERIVED

• 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.

  PMID: 36945773 DERIVED

• 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.

  PMID: 31477906 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Leukapheresis; Whole-Body Irradiation; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Radiotherapy; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Persis Amrolia

  UCL Institute of Child Health

  STUDY CHAIR

Central Study Contacts

Aniqa Tasnim

CONTACT

0203 108 4753; ctc.carpall@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2015
• First Posted: May 14, 2015
• Study Start: April 1, 2016
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2041
• Last Updated: April 2, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)