CAR-T Cell Therapy for Blood Cancers

Overseen By Christopher G Kanakry, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents, Checkpoint inhibitors

Disqualifiers: Active CNS cancer, Uncontrolled infection, others

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

Compensation: Varies

Number of Visits: 9

Duration: 4-6 weeks

155 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach for treating aggressive blood cancers, such as certain leukemias and lymphomas. It combines two treatments: a bone marrow transplant from a donor and CAR-T cell therapy, which uses modified immune cells to better target cancer. The trial aims to determine if these treatments together can improve outcomes. Individuals with aggressive blood cancers that express a specific protein called CD19 and have a related donor willing to assist may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding 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 information does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents within 3 weeks before starting the trial, and you must not have had prior checkpoint inhibitor therapy within 6 weeks before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study treated 43 patients with B cell cancers using CD19-targeted CAR T cells. These treatments were generally well-tolerated, though some side effects occurred. A few patients experienced cytokine release syndrome (CRS), where the immune system becomes overly active, leading to fever and tiredness. Most cases were mild and manageable. Another possible side effect, neurotoxicity, can cause confusion or headaches, but these were usually mild as well.

CAR T-cell therapies have been approved for other blood cancers, indicating a known safety profile. However, this trial is in an early phase, so the main goal is to closely monitor safety and determine the best dose. Participants will be carefully monitored for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CAR-T cell therapy for blood cancers because it represents a cutting-edge approach that uses genetically modified immune cells to target cancer. Unlike traditional treatments like chemotherapy and radiation, which can affect both healthy and cancerous cells, CAR-T therapy specifically reprograms a patient's T cells to recognize and attack cancer cells. This particular therapy uses a retroviral vector to deliver a CAR that targets the CD19 molecule found on many blood cancer cells, potentially improving precision and effectiveness. Moreover, this method holds promise for long-lasting remission, as these engineered T cells can persist and continue to patrol the body for cancer cells after initial treatment.

What evidence suggests that this trial's treatments could be effective for high-risk blood cancers?

Research has shown that CAR T-cell therapy, which targets a protein called CD19, offers promising results for treating blood cancers like leukemia and lymphoma. One study demonstrated significant improvements in patients with B-cell cancers, with many entering remission after treatment. Long-term results are also encouraging, with some patients remaining in remission for years. This trial will include participants receiving CAR-T cells at varying dose levels to determine the maximum tolerated dose (MTD) and further evaluate at the MTD. This therapy modifies a patient's immune cells to better identify and attack cancer cells with the CD19 protein. Early data and patient experiences suggest that this approach could offer new hope for those with high-risk blood cancers. ^{1 2 6 7 8}

Who Is on the Research Team?

Christopher G Kanakry, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults aged 18 to 75 with aggressive blood cancers that have CD19 on their surface. A half-matched related donor, who could be a parent, child, sibling or extended family member over the age of 12, is also required. Participants must pass heart and lung function tests among others.

Inclusion Criteria

Women of child-bearing potential must agree to use a highly effective method of contraception

Ability of participant to understand and sign a written informed consent document

Willingness to remain in the NIH hospital or stay close to the NIH for a minimum of 100 days after transplant

Exclusion Criteria

Participants living outside the US

Participants receiving any other investigational agents within 3 weeks prior to the beginning of conditioning

History of allergic reactions attributed to compounds of similar composition to study agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits for imaging scans, blood tests, and other exams

Treatment

Participants receive reduced intensity conditioning, HLA-haploidentical bone marrow HCT, GVHD prophylaxis including post-transplantation cyclophosphamide, and allogeneic donor-derived anti-CD19 CAR-T cells

4-6 weeks

Inpatient stay for 4-6 weeks

Initial Follow-up

Participants remain within a 1-hour drive of the hospital for frequent visits to monitor safety and effectiveness

2-3 months

Frequent visits during this period

Long-term Follow-up

Participants continue to have periodic follow-up visits to monitor relapse and survival outcomes

5 years

Periodic visits over 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• mCD19-CAR-CD28-CD3-zeta.(anti-CD19 CAR) retroviral vector-transduced allogeneic peripheral blood lymphocytes (PBL)

Trial Overview The study combines two treatments: alloHCT (bone marrow transplant from a donor) and CAR-T cell therapy (modified immune cells targeting cancer). Patients will receive these therapies in the hospital and take drugs to reduce complications post-treatment.

How Is the Trial Designed?

Group I: Phase I: Dose Expansion Experimental Treatment 8 Interventions

Participants receiving CAR-T cells at MTD

Group II: Phase I: Dose Escalation Experimental Treatment 8 Interventions

Participants receiving CAR-T cells at escalation/de-escalation dose levels to determine MTD

Group III: Donor Active Control 1 Intervention

Donors for Arms 1 and 2

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. nature.com nature.com/articles/s41571-023-00754-1

Long-term outcomes following CAR T cell therapy In our long-term follow-up study involving 43 patients with B cell malignancies who received CD19-targeted CAR T cells at the National Cancer ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4929923/

CD19-targeted CAR T-cell therapeutics for hematologic ... The MD Anderson Cancer Center group reported on 13 patients (ALL, n = 8; B-NHL, n = 3; CLL, n = 2) with active B-cell malignancies, some of whom had undergone ...

3. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-12651-6

CD19 CAR T cells for B cell malignancies: a systematic review ... CAR-T cells: early successes in blood cancer and challenges in solid tumors. Acta Pharm Sin B. 2021;11(5):1129–47. Article CAS PubMed Google ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1567576924008324

CAR-T cell therapy: Efficacy in management of cancers ... ... blood cancer patients. •. Encouraging ... CAR-T therapy across various hematologic malignancies have continued to report promising results.

5. aacrjournals.org aacrjournals.org/cancerres/article/85/12/2234/762878/Targeting-PRC2-Enhances-the-Cytotoxic-Capacity-of

Targeting PRC2 Enhances the Cytotoxic Capacity of Anti ... Supplementary data. Data from Targeting PRC2 Enhances the Cytotoxic Capacity of Anti-CD19 CAR T Cells against Hematologic Malignancies. 22 ...

6. ascopubs.org ascopubs.org/doi/10.1200/EDBK_320085

CAR T-Cell Therapy in Hematologic Malignancies: Clinical ... Clinical data have led to the regulatory approvals of CAR T cells for B-cell malignancies and multiple myeloma. •. Extensive clinical experience ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S088779631830172X

Risks and Benefits of Chimeric Antigen Receptor T-Cell ... CAR-T cell therapy investigating different cancer-specific targets have also shown some potential in studies of non-hematopoietic malignancies [6]. These ...

8. ehoonline.biomedcentral.com ehoonline.biomedcentral.com/articles/10.1186/s40164-024-00536-0

CAR-T cell combination therapies in hematologic malignancies Elevated BCL-2 levels promote cancer cell survival and growth, correlating with disease progression, metastasis, and adverse clinical outcomes ...