Using modified T cells to treat relapsed hairy cell leukemia

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

This study is testing a new treatment using modified T cells to see if it can help adults with relapsed hairy cell leukemia who haven't responded to other therapies.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: rituximab, moxetumomab, CAR T, chemotherapy, immunotherapy, radiation, Chimeric Antigen Receptor, cyclophosphamide, fludarabine
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT04815356 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and efficacy of anti-CD22 chimeric antigen receptor (CAR) T cell therapy in adults with relapsed or refractory hairy cell leukemia (HCL) and its variant. Participants will undergo a series of screenings, including medical history assessments, imaging scans, and blood tests, to determine their eligibility. If eligible, patients will receive an infusion of genetically modified T cells designed to target and attack cancer cells expressing the CD22 antigen. The study seeks to provide a new treatment option for patients who have not responded to standard therapies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of hairy cell leukemia or its variant who have not responded to or are ineligible for standard treatments.

Not a fit: Patients with early-stage hairy cell leukemia or those who have not yet undergone standard treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new hope for patients with relapsed or refractory hairy cell leukemia, potentially improving survival rates.

How similar studies have performed: Other studies have shown promising results with CAR T cell therapies targeting CD22 in different types of leukemia, indicating potential for success in this approach.

Eligibility criteria

* INCLUSION CRITERIA
* 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.
* Participants must have adequate organ function as defined below: Participants must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met. If participants exhibit minor lab abnormalities that are determined to be related to HCL (not therapy-related), then those participants will be allowed to participate

  * Total bilirubin \<= 3 ULN, unless consistent with Gilbert s (ratio between total and direct bilirubin \> 5)
  * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<= 3x upper limit of normal (ULN)
  * Alkaline phosphatase \< 2.5 ULN
  * Serum creatinine \<= 1.5 mg/dL or creatinine clearance \>= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal calculated using eGFR or measured
  * Serum albumin \> 2 g/dL
* Prothrombin time (PT)/International Normalized Ratio (INR) \< 2.5x ULN (if on warfarin, PT/INR \< 3.5x ULN; If on any other anticoagulation, PT \< 2.5x ULN
* Fibrinogen \>= 0.5x lower limit of normal
* Participants with CNS disease are eligible, with exceptions
* Participants with history of allogeneic stem cell transplantation are eligible if at least 100 days post-transplant, if there is no evidence of active graft-versus-host disease (GVHD) and no longer taking immunosuppressive agents for at least 30 days prior to initiation of study intervention.
* Women of childbearing potential (WOCBP) must agree to use effective contraception (barrier, hormonal, intrauterine device \[IUD\], abstinence, surgical sterilization) at the study entry and up to 12 months after the last dose of combined chemotherapy or 4 months after cells infusion, whichever is later.

Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 4 months after the last dose of study drug.

* Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 4 months after the last dose of study drug.
* Ability of participant to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA

* 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)

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Robert J Kreitman, M.D. — National Cancer Institute (NCI)
• Study coordinator: Olena S Sierra Ortiz

Conditions Hairy Cell Leukemia; Hairy Cell Leukemia Variant; CD-22 Expressing Tumor; Chimeric Antigen Receptor; Adoptive Immunotherapy