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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for people with hairy cell leukemia (HCL), a type of blood cancer. The treatment, CD22 CAR T-cell infusion, uses modified immune cells, called CAR T cells, to recognize and attack cancer cells. The goal is to determine if these modified cells are safe for patients with HCL. Suitable candidates for this trial include those with HCL who have not responded to other treatments or cannot receive them. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that CD22 CAR T-cell therapy may be effective for certain blood cancers. In studies with patients who have follicular and mantle cell lymphoma, this treatment was generally well-tolerated, and no severe side effects prevented doctors from increasing the treatment dose.

The therapy has also been tested in other situations with good safety results. Although this trial is just beginning for hairy cell leukemia, the absence of severe side effects in earlier studies offers some initial reassurance about its safety. However, this is a new area of research, and ongoing studies will continue to evaluate its safety specifically for hairy cell leukemia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hairy cell leukemia?

Unlike the standard treatments for hairy cell leukemia, which often involve chemotherapy or targeted therapies like cladribine and pentostatin, CD22 CAR T-cell therapy represents a novel approach. This treatment is unique because it harnesses the body's own immune cells, modifies them to specifically target and attack cancer cells marked by the CD22 protein. Researchers are excited about this therapy's potential to provide a more personalized and targeted attack on the leukemia cells, possibly leading to better outcomes with fewer side effects. Additionally, the dose escalation and expansion strategies might refine the treatment's effectiveness and safety, offering hope for a more durable remission.

What evidence suggests that CD22 CAR T-cell therapy might be an effective treatment for hairy cell leukemia?

Research has shown that CD22 CAR T-cell therapy holds promise for treating certain blood cancers. Studies have found that this therapy can lead to complete remission in patients whose cancers did not respond to previous treatments. In this trial, participants with hairy cell leukemia will receive CD22 CAR T-cell therapy, which targets the CD22 protein on cancer cells, helping the immune system recognize and attack them. Early results suggest that patients with similar conditions have experienced significant improvements. Although this therapy is still in the early testing stages for hairy cell leukemia, its success in other cancers offers hope. ^{2 5 6 7 8}

Who Is on the Research Team?

Robert J Kreitman, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

1.

ascopubs.org

ascopubs.org/doi/10.1200/PO-25-00269

Complete Response in Hairy Cell Leukemia to Anti-CD22 ...

Classic hairy cell leukemia (HCL) is a rare B-cell malignancy expressing CD11c, CD22, CD25, CD103, CD123, annexin A1 (Anxa1), and BRAF V600E ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04815356

NCT04815356 | Phase I Study of Anti-CD22 Chimeric ...

This will be the first trial of anti-CD22 CAR T-cell therapy in the treatment of relapsed/refractory HCL and HCLv. Objectives. To assess the safety and ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11610546/

Cell therapy for a rare disease- hairy cell leukemia variant

Our BAFF CAR-T cells are effective in preclinical models of mantle cell lymphoma, multiple myeloma, and acute lymphoblastic leukemia models, and ...

4.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/2064/529883/CD22-Directed-CAR-T-Cell-Therapy-Achieves-Complete

CD22-Directed CAR T-Cell Therapy Achieves Complete ...

CD22-directed CAR T-cell therapy achieves complete remission in CD19-directed CAR T-cell refractory follicular and mantle cell lymphoma.

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7280047/

Updated Results From a Phase I Anti-CD22 CAR T-Cell Trial

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

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12270311/

Complete Response in Hairy Cell Leukemia to Anti-CD22 ...

Classic hairy cell leukemia (HCL) is a rare B-cell malignancy expressing CD11c, CD22, CD25, CD103, CD123, annexin A1 (Anxa1), and BRAF V600E ...

7.

ccr.cancer.gov

ccr.cancer.gov/news/article/clinical-trial-researches-car-t-cell-therapy-for-hairy-cell-leukemia

Clinical trial researches CAR T-cell therapy for hairy cell ...

Investigators want to find out if the CARs can help T cells do a better job of identifying and attacking HCL cells throughout the body and if ...

8.

astctjournal.org

astctjournal.org/article/S2666-6367(25)00627-X/fulltext

CD22-Directed CAR T-Cell Therapy Achieves Complete ...

CAR22 therapy in FL & MCL is safe with no observed DLTs in all 6 patients. Efficacy is promising with 5 of 6 high-risk, CAR-exposed patients achieving CR.