Combining CAR-T Cells with Dendritic Cells for Relapsed Leukemia

A Clinical Study of Chimeric Antigen Receptor T Cells Combined With Eps8 Peptide Specific Dendritic Cell for Patients With Relapsed/Refractory Leukemia and Myelodysplastic Syndromes

This study is testing a new treatment that combines special immune cells with another type of immune cell to see if it can help people with leukemia that hasn't responded to other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Zhujiang Hospital (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, CART, Chimeric antigen receptor
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT03291444 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of combining Chimeric Antigen Receptor T cells with peptide-specific dendritic cells in patients with relapsed or refractory leukemia, including Acute Lymphoblastic Leukemia (ALL) and Acute Myelogenous Leukemia (AML). The trial focuses on patients who have not responded to standard chemotherapy and have specific antigen expressions. Key outcomes such as progression-free survival and overall response rates will be monitored to assess the treatment's efficacy.

Who should consider this trial

Good fit: Ideal candidates include patients with relapsed or refractory AML or ALL who have specific antigen expressions and have not achieved complete remission after standard chemotherapy.

Not a fit: Patients with leukemia who have not expressed the required antigens or who are not relapsed or refractory may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients with difficult-to-treat relapsed or refractory leukemia.

How similar studies have performed: Other studies have shown promising results with CAR-T cell therapies, suggesting potential for success with this combined approach.

Eligibility criteria

Inclusion Criteria:

1. Tumor type: Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) according to the WHO criteria (at least 20% blasts in the marrow). All FAB subtypes except M3. Patients with Myelodysplastic Syndrome, category of Refractory Anemia with Excess Blasts (RAEB): RAEB I (WHO: medullary blast count ≤ 10% and a peripheral blast count ≤ 5%) and RAEB II (WHO: medullary blast count \> 10% and/or \> 5% peripheral blasts) can be included in the study in absence of other non-experimental treatment modalities.
2. Positive antigen for any of CD19, CD20, CD22, CD10, CD33, CD38, CD56, CD117, CD123, CD34, or Muc1.Simultaneously ,high expression of EPS8 or WT1 in acute leukemia.
3. Relapsed/Refractory leukemia patients：

   * Did not achieve complete remission after 2 times of standard plan chemotherapy.
   * Relapsed after first induction chemotherapy.
   * Did not response to chemotherapy before HSCT or relapsed after HSCT.
   * Cannot receive allo-HSCT or refuse to receive allo-HSCT.
   * Relapsed after CAR-T cell infusion.
4. Age greater than 18 year and less than 80 years.
5. Objectively assessable parameters of life expectancy: more than 3 months.
6. Performance status: WHO PS grade 0-1 (ECOG performance status 0 or 1).
7. Meet the following criteria for apheresis：WBC \>= 3,000/L, Hb \>= 8.0 g/dL, platelet count \>= 80,000/mm3, \<= 600,000/mm3.
8. Pulmonary function: Peripheral blood oxygen saturation greater than 90%; Cardiac function: Left ventricular ejection fraction \>60%.
9. Prior and concomitant associated diseases allowed with the exception of underlying autoimmune disease and positive serology for HIV/HBV/HCV.
10. No concomitant use of immunosuppressive drugs.
11. Adequate renal and liver function, i.e. creatinin, bilirubin, and aminotransferase =\< 1.2 times the upper limit of normal.
12. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
13. Women of child-bearing potential should use adequate contraception prior to study entry and for the duration of study participation.
14. Written informed consent obtained.

Exclusion Criteria:

1. Patients with severe complications: cardiovascular disorders, respiratory disorders, renal dysfunction, immunodeficiency, hematological disorders, autoimmune diseases, sever allergy and severe infectious disease.
2. Patients who should receive systemic administration of steroid or immunosuppressive agents.
3. Presence of active brain metastases.
4. Pregnant, lactating, or possibly pregnant women, or willing to be pregnant.
5. Severe psychiatric disorder.
6. Active multiple cancers.
7. Patients have received other genetic therapy products.
8. Transfection efficiency was less than 30%.
9. Inappropriate for study entry judged by an attending physician.
10. patients who have sensitivity to drugs that provide local anesthesia.

Where this trial is running

Guangzhou, Guangdong

• Zhujiang Hospital, Southern Medical University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Yuhua Li, M.D, Ph.D — Zhujiang Hospital
• Study coordinator: Sanfang Tu, M.D, Ph.D

Conditions Leukemia, Acute Lymphocytic; Leukemia, Acute Myelogenous; Myelodysplastic Syndromes