Autologous CD22 CAR T Cells in Adults w/ Recurrent or Refractory B Cell Malignancies

NCT04088890 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: IRB-50836NCI-2019-068105K08CA248968-05
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to test whether CD22-CAR T cells can be successfully made from immune cells collected from adults with relapsed/refractory B-cell malignancies (leukemia and lymphoma).

Conditions

B-ALL; B-cell Non Hodgkin Lymphoma; DLBCL; Follicular Lymphoma Grade 3B

Keywords

CD22; CAR T cells

Outcome Measures

Primary Outcomes (3)

• Rate of Successful Manufacture of CD22 CAR T Cells

  The percentage of apheresis samples (fresh or frozen) that are successfully processed and expanded to manufacture CD22 CAR T cells will be determined for each dose cohort.

  7-11 days from start of manufacturing

• Incidence of Dose Limiting Toxicities (DLTs) in Subjects With Aggressive B-cell NHL

  Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD22 CAR T cells, as recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, at each dose level tested in subjects with aggressive B-cell NHL

  28 days after infusion

• Safety Evaluation of CD22-CAR T Cells in Subjects With ALL

  Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD22 CAR T cells, as recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, at each dose level tested in subjects with ALL

  28 days after infusion

Secondary Outcomes (2)

• Clinical Activity of CD22-CAR T Cells in Adults With Relapsed/Refractory CD22-expressing B-cell ALL at Target Dose

  28 days after infusion

• Clinical Activity of CD22-CAR T Cells in Adults With Relapsed/Refractory Aggressive B-cell NHL at MTD/RP2D

  3 months after infusion

Study Arms (2)

R/R ALL

EXPERIMENTAL

Relapsed/refractory ALL Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows: * Fludarabine 30 mg/m2 per day IV for days 5, 4, 3 * Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3 Autologous CD22 CAR T cells will be administered intravenously at Dose1: 3 x 10\^5cells/kg (± 20%) 10

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: CD22 CAR

R/R aggressive B-cell NHL

EXPERIMENTAL

Relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows: * Fludarabine 30 mg/m2 per day IV for days 5, 4, 3 * Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3 Autologous CD22-CAR T cells will be administered in 3 escalating doses (Dose Level 1, 2, and 3) to determine MTD/RP2D. Dose1: 1 x 10\^6 cells/kg (± 20%) Dose2: 3 x 10\^6 cells/kg (± 20%) Dose3: 1 x 10\^7 cells/kg (± 20%)

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: CD22 CAR

Interventions

Fludarabine DRUG

Fludarabine 30 mg/m2

R/R ALL; R/R aggressive B-cell NHL

Cyclophosphamide DRUG

Cyclophosphamide 500 mg/m2

R/R ALL; R/R aggressive B-cell NHL

CD22 CAR DRUG

Autologous T cells transduced with lentiviral vector (CD22.BB.Z) Chimeric Antigen Receptor (CD22 CAR). Autologous CD22 CAR T cells will be administered intravenously at Dose Level 1 in subjects with ALL. Autologous CD22-CAR T cells will be administered in 3 escalating doses (Dose Level 1, 2, and 3) in subjects with aggressive B-cell NHL to determine MTD/RP2D

R/R ALL; R/R aggressive B-cell NHL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Disease Status
• Disease Status of ALL
• Must have chemotherapy refractory disease defined as progression or stable disease after two lines of therapies, or relapsed disease after achieving CR.
• Subjects with persistent or relapsed minimal residual disease (MRD) (by flow cytometry, PCR, FISH, or next generation sequencing) require verification of MRD on two occasions at least 2 weeks apart.
• Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs).
• Subjects with recurrence of isolated CNS relapse after achieving complete remission (CR) are eligible.
• Disease Status of aggressive B-cell NHL •Histologically confirmed aggressive B cell NHL including the following types defined by WHO 2008: oDLBCL not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein Barr virus (EBV)+ DLBCL of the elderly; OR oprimary mediastinal (thymic) large B cell lymphoma; OR otransformation of follicular lymphoma, marginal zone lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma to DLBCL; OR oFollicular Lymphoma Grade 3B •Subjects with DLBCL, Follicular Lymphoma Grade 3B -or-
• Subjects with transformed FL, MZL, or CLL/SLL who HAVE NOT received chemotherapy prior to transformation:
• oMust have received an anthracycline regimen and an anti CD20 monoclonal antibody (unless documented CD20-negative) and be refractory or relapsed after second line of DLBCL treatment. Subjects with a partial response to second line therapy must be ineligible for autologous transplant.
• Subjects with transformed FL, MZL, or CLL/SLL who HAVE received anthracycline-containing chemotherapy prior to transformation: oMust have progressed, had SD or recurred with transformed disease after initial treatment for DLBCL.
• Measureable Disease
• Subjects with ALL: must have evaluable or measurable disease (MRD positive by flow cytometry, NGS, or PCR is acceptable).
• Subjects with aggressive B-cell NHL: must have evaluable or measurable disease according to the revised IWG Response Criteria for Malignant Lymphoma\[38\]. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
• CD22 expression
• Subjects with ALL: CD22 positive expression on malignant cells is required and must be detected by immunohistochemistry or 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 subject.

You may not qualify if:

• Recurrent or refractory ALL limited to isolated testicular disease.
• Hyperleukocytosis (≥ 50,000 blasts/μL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy.
• History of other malignancy, unless disease free for at least 3 years. At the discretion of the Principal Investigator, subjects in remission for 1-2 years prior to enrollment may be deemed eligible after considering the nature of other malignancy, likelihood of recurrence during one year following CAR therapy, and impact of prior treatment on risk of CD22-CAR T cells. Subjects in remission \<1 year are not eligible.
• Exception: Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) is eligible.
• Hormonal therapy in subjects in remission \> 1 year will be allowed.
• Presence of active fungal, bacterial, viral, or other infection requiring intravenous antimicrobials. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
• No knowledge of:
• HIV,
• Hepatitis B (HBsAg positive) or
• Hepatitis C virus (anti HCV positive) infection. A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
• Presence of cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement that in the judgment of the investigator may impair the ability to evaluate neurotoxicity.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
• Any medical condition that in the judgement of the sponsor investigator is likely to interfere with assessment of safety or efficacy of study treatment.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Women who are pregnant or breastfeeding.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• The Leukemia and Lymphoma Society: collaborator
• American Society of Hematology: collaborator
• Matthew Frank: lead

Study Sites (1)

Stanford Medical Center

Stanford, California, 94304, United States

Location

Related Publications (2)

• Frank MJ, Baird JH, Kramer AM, Srinagesh HK, Patel S, Brown AK, Oak JS, Younes SF, Natkunam Y, Hamilton MP, Su YJ, Agarwal N, Chinnasamy H, Egeler E, Mavroukakis S, Feldman SA, Sahaf B, Mackall CL, Muffly L, Miklos DB; CARdinal-22 Investigator group. CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy: a dose-finding phase 1 study. Lancet. 2024 Jul 27;404(10450):353-363. doi: 10.1016/S0140-6736(24)00746-3. Epub 2024 Jul 9.

  PMID: 38996463 DERIVED

• Baird JH, Frank MJ, Craig J, Patel S, Spiegel JY, Sahaf B, Oak JS, Younes SF, Ozawa MG, Yang E, Natkunam Y, Tamaresis J, Ehlinger Z, Reynolds WD, Arai S, Johnston L, Lowsky R, Meyer E, Negrin RS, Rezvani AR, Shiraz P, Sidana S, Weng WK, Davis KL, Ramakrishna S, Schultz L, Mullins C, Jacob A, Kirsch I, Feldman SA, Mackall CL, Miklos DB, Muffly L. CD22-directed CAR T-cell therapy induces complete remissions in CD19-directed CAR-refractory large B-cell lymphoma. Blood. 2021 Apr 29;137(17):2321-2325. doi: 10.1182/blood.2020009432.

  PMID: 33512414 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Matthew Frank, MD, PhD
• Organization: Stanford University

mjfrank@stanford.edu

(650) 498-8886

Study Officials

• Matthew Frank, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Study Record Dates

• First Submitted: September 11, 2019
• First Posted: September 13, 2019
• Study Start: September 12, 2019
• Primary Completion: November 7, 2024
• Study Completion: March 7, 2025
• Last Updated: March 30, 2026
• Results First Posted: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)