CD22 CAR T Cell Therapy for Hairy Cell Leukemia

Overseen By Olena S Sierra Ortiz

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Warfarin, Antineoplastics, Antibodies, others

Disqualifiers: Pregnancy, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

27 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

Is 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. ^{1 6 7 8 9}

How 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. ^{1 2 3 5 10}

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.

Research Team

Robert J Kreitman, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility 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.

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.

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

Treatment Details

Interventions

• CD22 CAR T-cell infusion

Trial Overview 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.

Participant Groups

Group I: Experimental therapy: Dose Expansion Experimental Treatment 1 Intervention

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

Group II: Experimental therapy: Dose Escalation Experimental Treatment 1 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

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

CD22-targeting CAR T-cell therapies show high complete response rates, with 68% in acute lymphoblastic leukemia (ALL) and 64% in non-Hodgkin's lymphoma (NHL), indicating their efficacy in treating these malignancies.

The incidence of severe side effects, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), is low, suggesting that these therapies are relatively safe, especially with dual-targeting CAR T-cells not increasing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells. Fergusson, NJ., Adeel, K., Kekre, N., et al.[2023]

In a study involving 58 children and young adults with relapsed or refractory B-cell malignancies, CD22-targeted CAR T cells achieved a complete remission rate of 70%, demonstrating significant efficacy as an alternative treatment for patients who did not respond to CD19-targeted therapies.

The treatment was generally safe, with most side effects being mild to moderate, although cytokine release syndrome occurred in 86.2% of participants, indicating the need for careful monitoring and potential toxicity management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Shah, NN., Highfill, SL., Shalabi, H., et al.[2021]

A novel T-cell receptor (TCR) targeting the CD22-derived peptide was identified, showing promise for treating B-cell malignancies by effectively recognizing and killing leukemia cells while sparing most healthy cells.

TCR-engineered T-cells demonstrated the ability to selectively target CD22-positive B-cell leukemia, suggesting a complementary approach to existing CAR and antibody therapies, although the presence of CD22 on some non-B-cells may pose challenges for this strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A CD22-reactive TCR from the T-cell allorepertoire for the treatment of acute lymphoblastic leukemia by TCR gene transfer. Jahn, L., Hagedoorn, RS., van der Steen, DM., et al.[2018]

A first-in-human trial of anti-CD22 CAR T-cell therapy in children and young adults with relapsed acute lymphocytic leukemia demonstrated that the treatment is feasible, safe, and effective, resulting in remissions for most patients.

The study found that infusing higher numbers of T cells was associated with better treatment responses, suggesting a dose-dependent effect in the therapy's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD22 CAR Therapy Leads to ALL Remissions. [2018]

CD19-targeted CAR-T therapy shows a high efficacy in treating refractory B-cell malignancies, with a complete remission rate of 55% and a partial remission rate of 25% based on a meta-analysis of 19 studies involving 391 patients.

While the treatment is effective, it is associated with manageable side effects, including fever (62%), hypotension (22%), and acute renal failure (24%), with no reported deaths due to toxicity, indicating a need for improved safety strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive Immunotherapy for B-cell Malignancies Using CD19- Targeted Chimeric Antigen Receptor T-Cells: A Systematic Review of Efficacy and Safety. Hao, L., Li, T., Chang, LJ., et al.[2019]

CAR-T cell therapy has shown effective tumor-killing activity in treating B cell-derived hematological tumors and is being explored for solid tumors, indicating its potential as a versatile cancer treatment.

However, the therapy can lead to serious and potentially life-threatening adverse events, highlighting the need for careful monitoring and management strategies in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse events and coping strategies of CAR-T cells in the treatment of malignant tumors. Chen, X., Li, P., Tian, B., et al.[2023]

Chimeric-antigen-receptor T cells (CAR-T) targeting CD19 are associated with several adverse drug reactions (ADRs), with the most common being cytokine release syndrome (CRS), neurological disorders, and hematological disorders, as identified in a study analyzing 1783 safety reports.

While CAR-T therapy can lead to severe ADRs, particularly in the week following administration, the overall fatality rate from these reactions is relatively low at 5.5%, though serious conditions like hemophagocytic-lymphohistiocytosis and infections require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells safety: A pharmacovigilance and meta-analysis study. Dolladille, C., Ederhy, S., Ezine, E., et al.[2021]

CAR T-cell therapy is a promising treatment for various cancers, including hematological malignancies and solid tumors, but it can lead to serious adverse reactions such as cytokine release syndrome (CRS) and neurotoxicity.

Understanding the mechanisms behind these adverse reactions is crucial for early identification and effective treatment, which is essential for the safe clinical application of CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reactions Related to CAR-T Cell Therapy. Miao, L., Zhang, Z., Ren, Z., et al.[2021]

CAR T cells have shown significant clinical effectiveness in treating blood cancers, but their success in solid tumors has been less impressive, highlighting the need for further research in this area.

While CAR T cell therapy can lead to serious side effects like cytokine release syndrome and neurological toxicity, some theoretical risks have not yet been observed in clinical settings, emphasizing the importance of managing known toxicities for safe treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and management in CAR T-cell therapy. Bonifant, CL., Jackson, HJ., Brentjens, RJ., et al.[2023]

The CD22/CD19 dual-targeting CAR-T-cell therapy showed a remarkable overall response rate of 97% and a complete remission rate of 93% in patients with relapsed/refractory acute lymphoblastic leukemia (ALL), based on a meta-analysis of 14 studies involving 405 patients.

For non-Hodgkin lymphoma (NHL), the therapy resulted in an overall response rate of 85% and a complete remission rate of 57%, with manageable side effects such as cytokine release syndrome occurring in 86% of patients, indicating both efficacy and tolerability of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Nguyen, TT., Thanh Nhu, N., Chen, CL., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

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]

3. United States pubmed.ncbi.nlm.nih.gov

A CD22-reactive TCR from the T-cell allorepertoire for the treatment of acute lymphoblastic leukemia by TCR gene transfer. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Anti-CD22 CAR Therapy Leads to ALL Remissions. [2018]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Adoptive Immunotherapy for B-cell Malignancies Using CD19- Targeted Chimeric Antigen Receptor T-Cells: A Systematic Review of Efficacy and Safety. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Serious adverse events and coping strategies of CAR-T cells in the treatment of malignant tumors. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells safety: A pharmacovigilance and meta-analysis study. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Reactions Related to CAR-T Cell Therapy. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Toxicity and management in CAR T-cell therapy. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

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]