CD22 CAR T Cell Therapy for Hairy Cell Leukemia
Recruiting in Palo Alto (17 mi)
Overseen byRobert J Kreitman, M.D.
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Warfarin, Antineoplastics, Antibodies, others
Disqualifiers: Pregnancy, HIV, Hepatitis, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had systemic chemotherapy, immunotherapy, or radiation therapy within 2 weeks before apheresis, and you cannot be taking warfarin.
What data supports the effectiveness of the treatment CD22 CAR T Cell Therapy for Hairy Cell Leukemia?
Research shows that CD22 CAR T-cell therapy has led to high remission rates in patients with acute lymphocytic leukemia (ALL) and non-Hodgkin's lymphoma (NHL), with complete response rates of 68% and 64% respectively. This suggests potential effectiveness for similar B-cell malignancies, like Hairy Cell Leukemia.
12345Is CD22 CAR T-cell therapy safe for humans?
CD22 CAR T-cell therapy has been studied in early phase trials for certain blood cancers, showing some serious side effects like cytokine release syndrome (CRS, a severe immune reaction) and neurological issues, but these were rare. While these side effects can be serious, they are generally manageable, and the therapy is considered safe enough to continue studying in clinical trials.
16789How is CD22 CAR T-cell therapy different from other treatments for hairy cell leukemia?
CD22 CAR T-cell therapy is unique because it uses genetically modified T-cells to specifically target the CD22 protein on cancer cells, offering a novel approach for patients who may not respond to traditional treatments. This therapy is part of a broader category of immunotherapies that harness the body's immune system to fight cancer, and it is particularly promising for those with limited options after other treatments have failed.
123510Eligibility Criteria
Adults over 18 with hairy cell leukemia (HCL) who have tried, can't receive, or refused other treatments. They must meet specific health criteria like normal organ function tests and not be pregnant or breastfeeding. Participants need to agree to use contraception and sign a consent form.Inclusion Criteria
My kidney function is within the normal range.
Fibrinogen greater than or equal to 0.5x lower limit of normal.
I can do most of my daily activities unless my illness prevents me.
+44 more
Exclusion Criteria
I do not have HIV, HBV, or HCV infections.
I am HIV positive.
I have tested positive for hepatitis B or C, but if I later test negative, I can still participate.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Multiple visits for various tests
Leukapheresis and Pre-treatment
Participants undergo leukapheresis to collect lymphocytes and receive pre-treatment evaluations
1 week
1 visit (in-person)
Lymphodepleting Chemotherapy
Participants receive fludarabine and cyclophosphamide as lymphodepleting chemotherapy
5 days
Daily visits for chemotherapy administration
CAR T-cell Infusion
Participants receive an infusion of anti-CD22 CAR T-cells and are monitored in the hospital
14 days
Inpatient stay for monitoring
Initial Follow-up
Participants have visits twice a week for 1 month post-infusion for monitoring
4 weeks
8 visits (in-person)
Extended Follow-up
Participants are followed closely for 6 months, then less frequently for at least 5 years
5 years
Regular visits as per protocol
Long-term Follow-up
Participants are monitored for long-term safety and efficacy for 15 years
15 years
Annual visits
Participant Groups
The trial is testing the safety of anti-CD22 CAR T cells in treating HCL. It involves screening tests, chemotherapy drugs infusion, followed by the experimental CAR T cell infusion, with hospital stay and follow-ups for up to 15 years.
2Treatment groups
Experimental Treatment
Group I: Experimental therapy: Dose ExpansionExperimental Treatment1 Intervention
Autologous anti-CD22-CAR T-cells at the MTD
Group II: Experimental therapy: Dose EscalationExperimental Treatment1 Intervention
Escalating doses of autologous anti-CD22-CAR T-cells in subjects to determine the MTD
CD22 CAR T-cell infusion is already approved in China for the following indications:
🇨🇳 Approved in China as Anti-CD22 CAR T-cell therapy for:
- Haematological malignancies
- Precursor B-cell lymphoblastic leukaemia-lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells. [2023]Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been FDA-approved, CAR T-cells targeting CD22, as well as dual-targeting CD19/CD22 CAR T-cells, are currently being evaluated in clinical trials. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD22-targeting CAR T-cell therapies. We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to March 3rd 2022 for full-length articles and conference abstracts of clinical trials employing CD22-targeting CAR T-cells in acute lymphocytic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The primary outcome was best complete response (bCR). A DerSimonian and Laird random-effects model with arcsine transformation was used to pool outcome proportions. From 1068 references screened, 100 were included, representing 30 early phase studies with 637 patients, investigating CD22 or CD19/CD22 CAR T-cells. CD22 CAR T-cells had a bCR of 68% [95% CI, 53-81%] in ALL (n= 116), and 64% [95% CI, 46-81%] in NHL (n= 28) with 74% and 96% of patients having received anti-CD19 CAR T-cells previously in ALL and NHL studies respectively. CD19/CD22 CAR T-cells had a bCR rate of 90% [95% CI, 84-95%] in ALL (n= 297) and 47% [95% CI, 34-61%] in NHL (n= 137). The estimated incidence of total and severe (grade ≥3) CRS were 87% [95% CI, 80-92%] and 6% [95% CI, 3-9%] respectively. ICANS and severe ICANS had an estimated incidence of 16% [95% CI, 9-25%] and 3% [95% CI, 1-5%] respectively. Early phase trials of CD22 and CD19/CD22 CAR T-cells show high remission rates in ALL and NHL. Severe CRS or ICANS were (1)rare and dual-targeting did not increase toxicity. Variability in CAR construct, dose, and patient factors amongst studies limits comparisons, with long-term outcomes yet to be reported.
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. [2021]Patients with B-cell acute lymphoblastic leukemia who experience relapse after or are resistant to CD19-targeted immunotherapies have limited treatment options. Targeting CD22, an alternative B-cell antigen, represents an alternate strategy. We report outcomes on the largest patient cohort treated with CD22 chimeric antigen receptor (CAR) T cells.
A CD22-reactive TCR from the T-cell allorepertoire for the treatment of acute lymphoblastic leukemia by TCR gene transfer. [2018]CD22 is currently evaluated as a target-antigen for the treatment of B-cell malignancies using chimeric antigen receptor (CAR)-engineered T-cells or monoclonal antibodies (mAbs). CAR- and mAbs-based immunotherapies have been successfully applied targeting other antigens, however, occurrence of refractory disease to these interventions urges the identification of additional strategies. Here, we identified a TCR recognizing the CD22-derived peptide RPFPPHIQL (CD22RPF) presented in human leukocyte antigen (HLA)-B*07:02. To overcome tolerance to self-antigens such as CD22, we exploited the immunogenicity of allogeneic HLA. CD22RPF-specific T-cell clone 9D4 was isolated from a healthy HLA-B*07:02neg individual, efficiently produced cytokines upon stimulation with primary acute lymphoblastic leukemia and healthy B-cells, but did not react towards healthy hematopoietic and nonhematopoietic cell subsets, including dendritic cells (DCs) and macrophages expressing low levels of CD22. Gene transfer of TCR-9D4 installed potent CD22-specificity onto recipient CD8+ T-cells that recognized and lysed primary B-cell leukemia. TCR-transduced T-cells spared healthy CD22neg hematopoietic cell subsets but weakly lysed CD22low-expressing DCs and macrophages. CD22-specific TCR-engineered T-cells could form an additional immunotherapeutic strategy with a complementary role to CAR- and antibody-based interventions in the treatment of B-cell malignancies. However, CD22 expression on non-B-cells may limit the attractiveness of CD22 as target-antigen in cellular immunotherapy.
Anti-CD22 CAR Therapy Leads to ALL Remissions. [2018]In a first-in-human trial of an anti-CD22 chimeric antigen receptor T-cell therapy in children and young adults with relapsed and refractory acute lymphocytic leukemia, researchers found that the immunotherapeutic approach was not only feasible and safe, but also effective, leading to remissions in most patients. Infusions of higher numbers of T cells correlated with improved responses.
Adoptive Immunotherapy for B-cell Malignancies Using CD19- Targeted Chimeric Antigen Receptor T-Cells: A Systematic Review of Efficacy and Safety. [2019]Adoptive infusion of chimeric antigen receptor transduced T- cells (CAR-T) is a powerful tool of immunotherapy for hematological malignancies, as evidenced by recently published and unpublished clinical results.
Serious adverse events and coping strategies of CAR-T cells in the treatment of malignant tumors. [2023]Chimeric antigen receptor T (CAR-T) cells technology has been successfully used in the treatment of B cell-derived hematological tumors and multiple myeloma. CAR-T cells are also being studied in a variety of solid tumors. Current clinical reports on CAR-T cells in the treatment of malignant tumors are abundant. The tumor-killing activity of CAR-T cells and the unique adverse effects of CAR-T cells have been confirmed by many studies. There is evidence that serious adverse events can be life-threatening. CAR-T cells therapy is increasingly used in clinical settings, so it is important to pay attention to its serious adverse events. In this review, we summarized the serious adverse events of CAR-T cells in the treatment of malignant tumors by reading literature and searching relevant clinical studies, and discussed the management and treatment of serious adverse events in an effort to provide theoretical support for clinicians who deal with such patients.
Chimeric antigen receptor T-cells safety: A pharmacovigilance and meta-analysis study. [2021]Chimeric-antigen-receptor T cells directed against CD19 (CAR-T) are emerging hematological therapeutics with scarce data on its overall safety profile spectrum. To determine the clinical features and incidence of adverse-drug reactions (ADR) associated with CAR-T. This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase and meta-analysis of data from CAR-T trials and cohorts in the literature was also performed through March, 2020. The primary objective was to identify ADR associated with approved CAR-T (axicabtagene-ciloleucel; tisagenlecleucel). We conducted a Bayesian disproportionate analysis with the 95% lower credibility-interval of information component (IC025 , significance > 0). We also performed a systematic-review and meta-analysis of CAR-T trials and cohorts in the literature to evaluate ADR incidence. Nine ADR classes were associated with CAR-T: Cytokine release syndrome (CRS, n = 1378, IC025  = 4.24), neurological disorders (n = 963, IC025  = 2.42), hematological disorders (n = 532, IC025  = 3.32), infections (n = 287, IC025  = 2.38), cardiovascular disorders (n = 256, IC025  = 2.81), pulmonary disorders (n = 186, IC025  = 3.80), reno-metabolic disorders (n = 123, IC025  = 1.89), hemophagocytic-lymphohistiocytosis (n = 36, IC025  = 5.01) and hepatic disorders (n = 32, IC025  = 2.49). ADR-related fatalities accounted for 99/1783 (5.5%) of the reports and 262/1783 (14.7%) for all-cause mortality. These ADR-related fatalities were associated with hemophagocytic-lymphohistiocytosis, cerebral vascular disorder, infections, and respiratory failure. In meta-analyses, the most frequent any-grade ADRs were CRS, hematological disorders, and neurological disorders. Fatal ADR were most found with neurological disorders, CRS, and infections. Note, CAR-T infusion may be associated with severe ADR mainly following the week of administration, though rarely fatal. Infections, hemophagocytic-lymphohistiocytosis and end organ failures including neurological or lung involvements require scrutiny.
Reactions Related to CAR-T Cell Therapy. [2021]The application of chimeric antigen receptor (CAR) T-cell therapy as a tumor immunotherapy has received great interest in recent years. This therapeutic approach has been used to treat hematological malignancies solid tumors. However, it is associated with adverse reactions such as, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), off-target effects, anaphylaxis, infections associated with CAR-T-cell infusion (CTI), tumor lysis syndrome (TLS), B-cell dysplasia, hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) and coagulation disorders. These adverse reactions can be life-threatening, and thus they should be identified early and treated effectively. In this paper, we review the adverse reactions associated with CAR-T cells, the mechanisms driving such adverse reactions, and strategies to subvert them. This review will provide important reference data to guide clinical application of CAR-T cell therapy.
Toxicity and management in CAR T-cell therapy. [2023]T cells can be genetically modified to target tumors through the expression of a chimeric antigen receptor (CAR). Most notably, CAR T cells have demonstrated clinical efficacy in hematologic malignancies with more modest responses when targeting solid tumors. However, CAR T cells also have the capacity to elicit expected and unexpected toxicities including: cytokine release syndrome, neurologic toxicity, "on target/off tumor" recognition, and anaphylaxis. Theoretical toxicities including clonal expansion secondary to insertional oncogenesis, graft versus host disease, and off-target antigen recognition have not been clinically evident. Abrogating toxicity has become a critical step in the successful application of this emerging technology. To this end, we review the reported and theoretical toxicities of CAR T cells and their management.
Effectiveness and safety of CD22 and CD19 dual-targeting chimeric antigen receptor T-cell therapy in patients with relapsed or refractory B-cell malignancies: A meta-analysis. [2023]The efficacy of CD22 or CD19 chimeric antigen receptor T (CAR-T) cells in the management of acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) was observed. Because antigen loss and lack of CAR-T-cell persistence are the leading causes of progressive disease following single-antigen targeting, we evaluated CD22/CD19 dual-targeting CAR-T-cell therapy efficacy and safety in relapsed/refractory B-cell malignancies.