Phase I Study of Anti-CD22 Chimeric Receptor T Cells in Patients With Relapsed/Refractory Hairy Cell Leukemia and Variant

NCT04815356 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 21001921-C-0019
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Background: CAR (Chimeric Antigen Receptor) T cell therapy is a type of cancer treatment in which a person s T cells (a type of immune cell) are changed in a laboratory to recognize and attack cancer cells. Researchers want to see if this treatment can help people with hairy cell leukemia (HCL). Objective: To test whether it is safe to give anti-CD22 CAR T cells to people with HCL. Eligibility: Adults ages 18 and older with HCL (classic or variant type) who have already had, are unable to receive, or have refused other standard treatments for their cancer. Design: Participants will be screened with the following: Medical history Physical exam Blood and urine tests Biopsy sample Electrocardiogram Echocardiogram Lung function tests Imaging scans Some screening tests will be repeated during the study. Participants may need to have a catheter placed in a large vein. Participants will have magnetic resonance imaging of the brain. Participants will have a neurologic evaluation and fill out questionnaires. Participants will have leukapheresis. Blood will be removed from the participant. A machine will divide whole blood into red cells, plasma, and lymphocytes. The lymphocytes will be collected. The remaining blood will be returned to the participant. Participants will get infusions of chemotherapy drugs. Participants will get an infusion of the anti-CD22 CAR T cells. They will stay at the hospital for 14 days. Then they will have visits twice a week for 1 month. After treatment, participants will be followed closely for 6 months, and then less frequently for at least 5 years. Then they will have long-term follow-up for 15 years.

Conditions

Hairy Cell Leukemia; Hairy Cell Leukemia Variant

Keywords

CD-22 Expressing Tumor; Chimeric Antigen Receptor; Adoptive Immunotherapy

Outcome Measures

Primary Outcomes (2)

• safety and feasibility

  Fraction of participants at each dose level who experience a toxicity along with the grades and types of toxicity and which can successfully manufacture the targeted dose number

  end of treatment

• antitumor effect

  The fraction of participants who experience a CR among the 10 evaluable participants treated at the MTD or highest safe dose

  every year for 15 years

Secondary Outcomes (7)

• expansion and persistence

  every year for 5 years

• MRD negative CR

  every year for 15 years

• duration of response

  every year for 15 years

• progression free-survival

  every year for 15 years

• event free survival

  every year for 15 years

Study Arms (2)

Experimental therapy: Dose Escalation

EXPERIMENTAL

Escalating doses of autologous anti-CD22-CAR T-cells in subjects to determine the MTD

Biological: CD22CART cell infusion

Experimental therapy: Dose Expansion

EXPERIMENTAL

Autologous anti-CD22-CAR T-cells at the MTD

Biological: CD22CART cell infusion

Interventions

CD22CART cell infusion BIOLOGICAL

The treatment regimen will consist of lymphodepleting chemotherapy followed by CD22CART infusion: Days -4 to -2: fludarabine 25 mg/m2/dose Day -2: cyclophosphamide 900 mg/m2/dose Day 0: CD22CART infusion (starting at dose level 1 \[DL1\]: 1 x 105 transduced CAR-T cells/kg) on Day 0 participants will be evaluated for response at Day 28 post-CD22CART infusion.

Experimental therapy: Dose Escalation; Experimental therapy: Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of HCL or HCLv according to morphological and immunophenotypic criteria of WHO classification \[WHO, 2008 revised 2016\] of lymphoid neoplasm.
• Participants should have any of the following indications for therapy:
• ANC \<1/nL,
• Hemoglobin \<10g/dL,
• Platelets\<100/nL,
• Symptomatic splenomegaly,
• HCL mass with short axis \> 2 cm outside or \>0.5 cm inside the CNS,
• HCL/HCLv count \>5/nL in blood or \>25/mm\^3 in CSF,
• HCL/HCLv count doubling time \<6 months and increasing lytic or blastic bone lesions
• Participants who have eligible blood counts within 4 weeks from the initiation of study will not be considered ineligible if subsequent blood counts prior to enrollment fluctuate and become ineligible up until the time of enrollment.
• HCL/HCLv, after prior treatment with, ineligible for, refusal of, or inability to obtain 1)rituximab given concurrently with or sequentially after purine analog, 2) moxetumomab pasudotox-tdft, and 3) BRAF-inhibition.
• CD22 expression must be detected on greater than 80% of malignant cells by flow cytometry.
• Participants must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease (MRD) detected by flow cytometry or immunohistochemistry.
• Age \>=18 years
• ECOG performance \<=2 (Karnofsky \>=60%, see Appendix A), participants are exempt from this criterion if poor performance status is related to HCL.

You may not qualify if:

• Pregnancy
• Systemic chemotherapy, immunotherapy, or radiation therapy \<= 2 weeks prior to apheresis with the following exception:
• Participants receiving steroids may be enrolled, provided there has been no increase in dose for at least 1 week prior to starting apheresis;
• For radiation therapy: Radiation therapy must have been completed at least 3 weeks prior to enrollment (including CNS radiation), with the exception that there is no time restriction if the volume of bone marrow treated is less than 10% and also the participant has measurable/evaluable disease outside the radiation port.
• Other anti-neoplastic investigational agents, or antibody-based therapies currently or within 2 weeks prior to apheresis
• Participants taking warfarin
• Prior CAR therapy within 30 days prior to apheresis or prior CAR therapy at any time with evidence for persistence of CAR T cells in blood samples (circulating levels of genetically modified cells of \>= 5% by flow cytometry)
• Seropositive for human immunodeficiency virus (HIV) antibody. (Participants with HIV are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy in the future should study results indicate effectiveness.)
• Seropositive for hepatitis C virus (HCV) or positive for hepatitis B surface antigen (HbsAG). Participants who convert to negative will not be excluded for history of positive test.
• Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, asthma, chronic obstructive pulmonary disease, 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
• 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia, Hairy Cell

Condition Hierarchy (Ancestors)

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

Study Officials

• Robert J Kreitman, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olena S Sierra Ortiz

CONTACT

(240) 858-3185; olena.sierraortiz@nih.gov

Robert J Kreitman, M.D.

CONTACT

(301) 648-7375; kreitmar@mail.nih.gov

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: March 24, 2021
• First Posted: March 25, 2021
• Study Start: May 23, 2022
• Primary Completion (Estimated): December 1, 2036
• Study Completion (Estimated): December 1, 2036
• Last Updated: May 5, 2026

Record last verified: 2026-05-01

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)