NHLPhase 1NCT02315612
Anti-CD22 Chimeric Receptor T Cells in Pediatric and Young Adults With Recurrent or Refractory CD22-expressing B Cell Malignancies
A Phase 1 study testing CD22-CAR in people with NHL and Large Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 39 years
- Conditions the study is for
- NHL, Large Cell Lymphoma, Follicular Lymphoma
- What is being tested?
- CD22-CAR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Dec 2014to 29 Oct 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 39 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
- Subjects with CNS disease are eligible, with exceptions as noted in the exclusion criteria
- 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.
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- 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
- between 6 and 10 years old: maximum serum creatinine 1.0mg/dL
- greater than 10 years old: maximum serum creatinine 1.2mg/dL
- 10. Patients previously treated with anti-CD19 CAR or other adoptive cell therapies will be eligible if all other eligibility criteria in the expansion phase. Circulating CAR T cells must be <5% in peripheral blood.
Who cannot join
- Subjects meeting any of the following criteria are not eligible for participation in the study:
- Subjects with radiologically-detected active CNS lymphoma, leptomeningeal CNS disease or isolated CNS disease which are eligible for definitive CNS directed radiationtherapy will be excluded.
- Hyperleukocytosis (greater than or equal to 50,000 blasts/ L) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy;
- Pregnant or breast-feeding females
- Recent prior therapy
- Subjects will be excluded related to the following prior therapy criteria:
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- Systemic chemotherapy, anti-neoplastic investigational agents, or antibody based therapies <= 2 weeks (6 weeks for clofarabine or nitrosoureas) prior to apheresis with the following exception:
- --No time restriction with prior intrathecal chemotherapy, steroid therapy, hydroxyurea or ALL maintenance type chemotherapy (vincristine, 6-mercaptopurine, oral methotrexate, or a tyrosine kinase inhibitor for patients with Ph+ ALL) provided there is recovery from any acute toxic effects.
- Radiation therapy <= 3 weeks prior to apheresis with the following exception:
- --No time restriction with radiation therapy if the volume of bone marrow treated is less than 10% and the subject has measurable/evaluable disease outside the radiation window.
- History of allogeneic stem cell transplantation prior to apheresis that meet the following criteria:
- Less than 100 days post-transplant
- Evidence of active graft-versus-host disease (GVHD)
- Taking immunosuppressive agents within 30 days prior to apheresis.
- Less than 6 weeks post donor lymphocyte infusion (DLI)
- History of prior CAR therapy or other adoptive cell therapies prior to apheresis that meet the following criteria:
- Less than 30 days post-infusion
- Circulating CAR T cells (or genetically modified cells) >=5% by flow cytometry in peripheral blood
- HIV/HBV/HCV Infection:
- Seropositive for HIV antibody. (Patients with HIV are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy in the future should study results indicate effectiveness.)
- Positive for Hepatitis B surface antigen (HbsAG)
- Evidence of active HCV (evidenced by detectable HCV RNA)
- Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject;
- Second malignancy other than in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least two years previously and subject is in remission;
- History of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study or in the manufacturing of the cells (i.e. gentamicin)
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase I Dose Escalation Study of Anti-CD22 Chimeric Receptor T Cells in Pediatric and Young Adults With Recurrent or Refractory CD22-expressing B Cell Malignancies
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.
Read more
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.
Read the detailed description
Background:
- Adoptive cellular therapy with T cells genetically modified using viral-based vectors to express chimeric antigen receptors targeting the CD19 molecule have demonstrated dramatic clinical responses in patients with acute lymphoblastic leukemia (ALL). However, not all patients respond and CD19-negative escape has been observed following CD19 CAR therapy, as well as anti-CD19/CD3 bispecific antibody therapy. Thus, additional targets are needed.
- CD22 is a B-lineage-restricted, transmembrane phosphoglycoprotein of the Ig superfamily that is widely expressed on B-cell malignancies including 96% to 100% of pediatric Bprecursor ALL. Therefore, CD22 represents a promising target. Encouraging responses targeting CD22 with an antibody based immunoconjugate have been seen in patients, including children, with recurrent and refractory ALL. This will be the first in human testing of anti-CD22 CAR adoptive cell therapy.
Objectives:
- To determine the feasibility of producing anti-CD22 CAR cells meeting established release criteria. Complete
- To assess the safety of administering escalating doses of anti-CD22-CAR engineered T cells in children and young adults with recurrent or refractory CD22- expressing B cell malignancies following a cyclophosphamide/fludarabine preparative regimen.
Eligibility:
- Patients 3-39 years of age, at least 14.5 kg, with CD22-expressing B-cell malignancies that have recurred after or not responded to one or more standard regimens and deemed incurable by standard therapy. Patients with a history of allogeneic hematopoietic transplantation (SCT) who meet all eligibility criteria are eligible to participate. Patients previously treated with anti-CD19 CAR engineered T cells are also eligible.
Design:
- PBMC will be obtained by leukapheresis, CD3+ cells enriched and cultured in the presence of anti-CD3/-CD28 beads followed by lentiviral vector supernatant containing the anti-CD22 (M971BBz) CAR.
- On Day -4 (cell infusion is Day 0), patients will begin induction chemotherapy comprising fludarabine 25 mg/m2 on Days -4, -3, and -2 and cyclophosphamide 900 mg/m2 on day -2.
- The CD22-CAR cells will be infused on Day 0, with up to a 72h delay allowed for infusion of fresh cells or a 7 day delay if cells are cryopreserved, if needed for resolution of clinical toxicities, to generate adequate cell numbers, or to facilitate scheduling.
- A phase I cell dose escalation scheme will be performed using 3 dose levels (3 x 10(5) transduced T cells/kg; 1 x 10(6) transduced T cells/kg; and 3 x 10(6) transduced T cells/kg;). If 2/6 patients have DLT at dose level 1, safety will be evaluated in a de-escalated dose of 1 x 10(5) transduced T cells/kg (more or less 20%)). Once the maximum tolerated dose (or highest level evaluated) is reached, enrollment into an expansion cohort of a total of 83 patients at MTD will proceed to provide additional information regarding the feasibility, safety and efficacy of this treatment.
- Patients will be monitored for toxicity, response and T cell persistence as well as other biologic correlates.
- Conditions
- NHL, Large Cell Lymphoma, Follicular Lymphoma, ALL, B-All, B-precursor ALL
- Being tested
- CD22-CAR
- Keywords
- Lymphoma, Chimeric Antigen Receptor, CD-22 Expressing Tumor, ALL, Adoptive Immunotherapy, B-All, Acute Lymphoblastic Leukemia, Acute Lymphocytic Leukemia, B-Non Hodgkin Lymphoma
- Medical subject headings
- Dendritic Cell Sarcoma, Interdigitating, Lymphoma, Follicular, Burkitt Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD22-CARBiological
CD22-CAR cells will be infused on Day 0 after induction chemotherapy regimen.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | dose escalation of CD22-CAR Receives: Biological: CD22-CAR |
| Arm 2 | Experimental | dose expansion of CD22-CAR Receives: Biological: CD22-CAR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity
Number of patients who have grade 3 CRS and above
Measured: End of treatment
Response
Number of patients who have complete and partial remission
Measured: 1 month, 3 months, and 6 months following CAR infusion
Secondary outcomes (3)
Safety and Toxicity
Number of patients who have detectable CAR cells
Measured: 1 month, 3 months and 6 months following CAR infusion
Objective Response (Complete + Partial Remission)
The number of patients who have complete and partial remissions
Measured: 1 month, 3 months and 6 months following CAR infusion
CAR-T cell Persistence
The number of patients who have detectable CAR cells
Measured: 1 month, 3 months and 6 months following CAR infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2014 (estimated)
- Study start12 Dec 2014
- Primary completion3 Apr 2019
- Study completion29 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for NHLStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Nirali N Shah, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02315612
- Sponsor's protocol ID
- 150029
- Other IDs
- 15-C-0029
- Status last verified
- Apr 2026
- First submitted
- 11 Dec 2014
- Last updated
- 28 Apr 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request.
Publications
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.
PubMed 23243285Bang 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.
PubMed 15746059Kalos 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.
PubMed 23890063Dreyzin 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.
PubMed 41411486Silbert 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.
PubMed 37486616Jess 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.
PubMed 37295816Molina 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.
PubMed 34687939Masih 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.
PubMed 34309174Shah 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.
PubMed 32286905
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Escalation Study of Anti-CD22 Chimeric Receptor T Cells in Pediatric and Young Adults With Recurrent or Refractory CD22-expressing B Cell Malignancies
- ClinicalTrials.gov ID
- NCT02315612
- Acronym / sponsor ID
- 150029
- Conditions
- NHL, Large Cell Lymphoma, Follicular Lymphoma, ALL, B-All, B-precursor ALL
- Keywords
- Lymphoma, Chimeric Antigen Receptor, CD-22 Expressing Tumor, ALL, Adoptive Immunotherapy, B-All, Acute Lymphoblastic Leukemia, Acute Lymphocytic Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 12 Dec 2014 (actual)
- Primary completion
- 3 Apr 2019 (actual)
- Study completion
- 29 Oct 2024 (actual)
- First posted
- 12 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background:
- Adoptive cellular therapy with T cells genetically modified using viral-based vectors to express chimeric antigen receptors targeting the CD19 molecule have demonstrated dramatic clinical responses in patients with acute lymphoblastic leukemia (ALL). However, not all patients respond and CD19-negative escape has been observed following CD19 CAR therapy, as well as anti-CD19/CD3 bispecific antibody therapy. Thus, additional targets are needed.
- CD22 is a B-lineage-restricted, transmembrane phosphoglycoprotein of the Ig superfamily that is widely expressed on B-cell malignancies including 96% to 100% of pediatric Bprecursor ALL. Therefore, CD22 represents a promising target. Encouraging responses targeting CD22 with an antibody based immunoconjugate have been seen in patients, including children, with recurrent and refractory ALL. This will be the first in human testing of anti-CD22 CAR adoptive cell therapy.
Objectives:
- To determine the feasibility of producing anti-CD22 CAR cells meeting established release criteria. Complete
- To assess the safety of administering escalating doses of anti-CD22-CAR engineered T cells in children and young adults with recurrent or refractory CD22- expressing B cell malignancies following a cyclophosphamide/fludarabine preparative regimen.
Eligibility:
- Patients 3-39 years of age, at least 14.5 kg, with CD22-expressing B-cell malignancies that have recurred after or not responded to one or more standard regimens and deemed incurable by standard therapy. Patients with a history of allogeneic hematopoietic transplantation (SCT) who meet all eligibility criteria are eligible to participate. Patients previously treated with anti-CD19 CAR engineered T cells are also eligible.
Design:
- PBMC will be obtained by leukapheresis, CD3+ cells enriched and cultured in the presence of anti-CD3/-CD28 beads followed by lentiviral vector supernatant containing the anti-CD22 (M971BBz) CAR.
- On Day -4 (cell infusion is Day 0), patients will begin induction chemotherapy comprising fludarabine 25 mg/m2 on Days -4, -3, and -2 and cyclophosphamide 900 mg/m2 on day -2.
- The CD22-CAR cells will be infused on Day 0, with up to a 72h delay allowed for infusion of fresh cells or a 7 day delay if cells are cryopreserved, if needed for resolution of clinical toxicities, to generate adequate cell numbers, or to facilitate scheduling.
- A phase I cell dose escalation scheme will be performed using 3 dose levels (3 x 10(5) transduced T cells/kg; 1 x 10(6) transduced T cells/kg; and 3 x 10(6) transduced T cells/kg;). If 2/6 patients have DLT at dose level 1, safety will be evaluated in a de-escalated dose of 1 x 10(5) transduced T cells/kg (more or less 20%)). Once the maximum tolerated dose (or highest level evaluated) is reached, enrollment into an expansion cohort of a total of 83 patients at MTD will proceed to provide additional information regarding the feasibility, safety and efficacy of this treatment.
- Patients will be monitored for toxicity, response and T cell persistence as well as other biologic correlates.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Biological: CD22-CARdose escalation of CD22-CAR |
| Arm 2 | Experimental | Biological: CD22-CARdose expansion of CD22-CAR |
Who may qualify
- Ages
- 3 to 39 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (23 listed)
- 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:
- Liver Function:
- 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.
Key exclusion criteria (25 listed)
- Subjects meeting any of the following criteria are not eligible for participation in the study:
- Subjects with radiologically-detected active CNS lymphoma, leptomeningeal CNS disease or isolated CNS disease which are eligible for definitive CNS directed radiationtherapy will be excluded.
- Hyperleukocytosis (greater than or equal to 50,000 blasts/ L) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy;
- Pregnant or breast-feeding females
- Recent prior therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD22-CARCD22-CAR cells will be infused on Day 0 after induction chemotherapy regimen. | Biological | Arm 1, Arm 2 |
Primary outcome
Toxicity
Time frame: End of treatment
Number of patients who have grade 3 CRS and above
Response
Time frame: 1 month, 3 months, and 6 months following CAR infusion
Number of patients who have complete and partial remission
3 secondary outcomes
Safety and Toxicity
Time frame: 1 month, 3 months and 6 months following CAR infusion
Objective Response (Complete + Partial Remission)
Time frame: 1 month, 3 months and 6 months following CAR infusion
CAR-T cell Persistence
Time frame: 1 month, 3 months and 6 months following CAR infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2026.
- Background: PubMed 23243285Haso 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.
- Background: PubMed 15746059Bang 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.
- Background: PubMed 23890063Kalos 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.
- Derived from this study: PubMed 41411486Dreyzin 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.
- Derived from this study: PubMed 37486616Silbert 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.
- Derived from this study: PubMed 37295816Jess 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.
- Derived from this study: PubMed 34687939Molina 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.
- Derived from this study: PubMed 34309174Masih 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.
- Derived from this study: PubMed 32286905Shah 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD recorded in the medical record will be shared with intramural investigators upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nirali N Shah, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD22-CAR in people with NHL and Large Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity (time frame: End of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02315612, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.