Anti-CD22 Chimeric Receptor T Cells in Pediatric and Young Adults With Recurrent or Refractory CD22-expressing B Cell Malignancies

NCT02315612 | Completed Phase 1 FDA Drug

• 2 other identifiers: 15002915-C-0029
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- One type of cancer therapy takes blood cells from a person, changes them in a lab, then gives the cells back to the person. In this study, researchers are using an anti-CD22 gene, a virus, and an immune receptor to change the cells. Objective: \- To see if giving anti-CD22 Chimeric Antigen Receptor (CAR) cells to young people with certain cancers is safe and effective. Eligibility: \- People ages 1-39 with a leukemia or lymphoma that has not been cured by standard therapy. Design:

• Participants will be screened to ensure their cancer cells express the CD22 protein. They will also have medical history, physical exam, blood and urine tests, heart tests, scans, and x-rays. They may give spinal fluid or have bone marrow tests.
• Participants may have eye and neurologic exams.
• Participants will get a central venous catheter or a catheter in a large vein.
• Participants will have white blood cells removed. Blood is removed through a needle in an arm. White blood cells are removed. The rest of the blood is returned by needle in the other arm.
• The cells will be changed in a laboratory.
• Participants will get two IV chemotherapy drugs over 4 days. Some will stay in the hospital for this.
• All participants will be in the hospital to get anti-CD22 CAR cells through IV. They will stay until any bad side effects are gone.
• Participants will have many blood tests. They may repeat some screening exams.
• Participants will have monthly visits for 2-3 months, then every 3-6 months. They may repeat some screening exams.
• Participants will have follow-up for 15 years.

Conditions

ALL; B-All; Acute Lymphocytic Leukemia; B-NHL; Follicular Lymphoma; B-precursor ALL; Acute Lymphoblastic Leukemia; B-Non Hodgkin Lymphoma; NHL; Large Cell Lymphoma

Keywords

Lymphoma; Chimeric Antigen Receptor; CD-22 Expressing Tumor; ALL; Adoptive Immunotherapy; B-All; Acute Lymphoblastic Leukemia; Acute Lymphocytic Leukemia; B-Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Toxicity

  Number of patients who have grade 3 CRS and above

  End of treatment

• Response

  Number of patients who have complete and partial remission

  1 month, 3 months, and 6 months following CAR infusion

Secondary Outcomes (3)

• Safety and Toxicity

  1 month, 3 months and 6 months following CAR infusion

• Objective Response (Complete + Partial Remission)

  1 month, 3 months and 6 months following CAR infusion

• CAR-T cell Persistence

  1 month, 3 months and 6 months following CAR infusion

Study Arms (2)

Arm 1

EXPERIMENTAL

dose escalation of CD22-CAR

Biological: CD22-CAR

Arm 2

EXPERIMENTAL

dose expansion of CD22-CAR

Biological: CD22-CAR

Interventions

CD22-CAR BIOLOGICAL

CD22-CAR cells will be infused on Day 0 after induction chemotherapy regimen.

Arm 1; Arm 2

Eligibility Criteria

• Age: 3 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patient must have a B cell ALL (inclusive of ALL blast transformation from CML) or lymphoma and must have relapsed or refractory disease after at least one standard chemotherapy regimen and one salvage regimen. In view of the PI and the primary oncologist, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, recurred after SCT, or have disease activity that prohibits SCT at the time of enrollment.
• CD22 expression must be detected on greater than 15% of the malignant cells by immunohistochemistry or greater than 80% by flow cytometry. The choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each patent. In general, immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples and CSF when feasible.
• Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
• Greater than or equal to 3 years of age (and at least 14.5 kg) and less than or equal to 39 years of age at time of enrollment.

You may not qualify if:

• Patients, parents/guardian(s), legally authorized representative (LAR), or durable power of attorney must be able to give consent and sign the informed consent document.
• Clinical performance status: Patients greater than or equal to 16 years of age: Karnofsky greater than or equal to 50%; Patients \< 16 years of age: Lansky scale greater than or equal to 50%. Subjects who are unable to walk because of paralysis, but who are upright in a wheelchair will be considered ambulatory for the purpose of calculating the performance score.
• Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for 12 months after receiving the preparative regimen for women and for 4 months for the same for men.
• Patients must have adequate organ function as described below:
• Cardiac function: Left ventricular ejection fraction greater than or equal to 45% or fractional shortening greater than or equal to 28%.
• Pulmonary function: Patients without respiratory symptoms (e.g. dyspnea at rest, known requirement for supplemental oxygen therapy) and who have an oxygen saturation greater than or equal to 92% on room air, will be eligible. For patients not meeting this criteria, pulmonary function tests will be performed to confirm that the DLCO/VA/Adj is 50% of the normal predicted value corrected for hemoglobin and alveolar volume in order to meet eligibility.(For children who are unable to cooperate for PFTs, the criterion is: No evidence of dyspnea at rest, no exercise intolerance and no requirement for supplemental oxygen therapy. )
• Hematologic function:
• Absolute neutrophil count greater than or equal to 750/mcL
• Platelets greater than or equal to 50,000/mcl
• A subject will not be excluded because of pancytopenia related to disease
• Liver Function:
• AST (SGOT)/ALT (SGPT): less than or equal to 20 x institutional upper limit of normal
• Total bilirubin less than or equal to 2 x ULN (except in the case of subjects with documented Gilbert s disease greater than or equal to 3 x ULN)
• Renal Function: Normal creatinineCreatinine level \< the maximum for age listed in the table below OR creatinine clearance greater than or equal to 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
• less than or equal to 5 years old: maximum serum creatinine 0.8mg/dL

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (9)

• Haso W, Lee DW, Shah NN, Stetler-Stevenson M, Yuan CM, Pastan IH, Dimitrov DS, Morgan RA, FitzGerald DJ, Barrett DM, Wayne AS, Mackall CL, Orentas RJ. Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood. 2013 Feb 14;121(7):1165-74. doi: 10.1182/blood-2012-06-438002. Epub 2012 Dec 14.

  PMID: 23243285 BACKGROUND

• Bang S, Nagata S, Onda M, Kreitman RJ, Pastan I. HA22 (R490A) is a recombinant immunotoxin with increased antitumor activity without an increase in animal toxicity. Clin Cancer Res. 2005 Feb 15;11(4):1545-50. doi: 10.1158/1078-0432.CCR-04-1939.

  PMID: 15746059 BACKGROUND

• Kalos M, June CH. Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology. Immunity. 2013 Jul 25;39(1):49-60. doi: 10.1016/j.immuni.2013.07.002.

  PMID: 23890063 BACKGROUND

• Dreyzin A, Yates B, Shalabi H, Silbert SK, Wang HW, Yuan CM, Hoang CN, Culbert AA, Gava F, Nair MS, Giordani VM, Little L, Foley T, Nussenblatt V, Fry TJ, Stroncek DF, Highfill SL, Shah NN. Ten-year experience of CD22 CAR T cells for children and young adults with B-cell acute lymphoblastic leukemia. Blood Adv. 2026 Mar 10;10(5):1700-1712. doi: 10.1182/bloodadvances.2025017753.

  PMID: 41411486 DERIVED

• Silbert SK, Madan S, Holland EM, Steinberg SM, Little L, Foley T, Epstein M, Sarkisian A, Lee DW, Nikitina E, Kakumanu S, Ruppin E, Shalabi H, Yates B, Shah NN. A comprehensive analysis of adverse events in the first 30 days of phase 1 pediatric CAR T-cell trials. Blood Adv. 2023 Sep 26;7(18):5566-5578. doi: 10.1182/bloodadvances.2023009789.

  PMID: 37486616 DERIVED

• Jess J, Yates B, Dulau-Florea A, Parker K, Inglefield J, Lichtenstein D, Schischlik F, Ongkeko M, Wang Y, Shahani S, Cullinane A, Smith H, Kane E, Little L, Chen D, Fry TJ, Shalabi H, Wang HW, Satpathy A, Lozier J, Shah NN. CD22 CAR T-cell associated hematologic toxicities, endothelial activation and relationship to neurotoxicity. J Immunother Cancer. 2023 Jun;11(6):e005898. doi: 10.1136/jitc-2022-005898.

  PMID: 37295816 DERIVED

• Molina JC, Steinberg SM, Yates B, Lee DW, Little L, Mackall CL, Shalabi H, Shah NN. Factors Impacting Overall and Event-Free Survival following Post-Chimeric Antigen Receptor T Cell Consolidative Hematopoietic Stem Cell Transplantation. Transplant Cell Ther. 2022 Jan;28(1):31.e1-31.e9. doi: 10.1016/j.jtct.2021.10.011. Epub 2021 Oct 20.

  PMID: 34687939 DERIVED

• Masih KE, Ligon JA, Yates B, Shalabi H, Little L, Islam Z, Ombrello AK, Inglefield J, Nussenblatt V, Manion M, Khan J, Shah NN. Consequences of hemophagocytic lymphohistiocytosis-like cytokine release syndrome toxicities and concurrent bacteremia. Pediatr Blood Cancer. 2021 Oct;68(10):e29247. doi: 10.1002/pbc.29247. Epub 2021 Jul 26.

  PMID: 34309174 DERIVED

• Shah NN, Highfill SL, Shalabi H, Yates B, Jin J, Wolters PL, Ombrello A, Steinberg SM, Martin S, Delbrook C, Hoffman L, Little L, Ponduri A, Qin H, Qureshi H, Dulau-Florea A, Salem D, Wang HW, Yuan C, Stetler-Stevenson M, Panch S, Tran M, Mackall CL, Stroncek DF, Fry TJ. 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. J Clin Oncol. 2020 Jun 10;38(17):1938-1950. doi: 10.1200/JCO.19.03279. Epub 2020 Apr 14.

  PMID: 32286905 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Dendritic Cell Sarcoma, Interdigitating; Lymphoma, Follicular; Burkitt Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Lymphoma, Non-Hodgkin; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Study Officials

• Nirali N Shah, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2014
• First Posted: December 12, 2014
• Study Start: December 12, 2014
• Primary Completion: April 3, 2019
• Study Completion: October 29, 2024
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (1)