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RecruitingNCT03291444Updated Mar 15, 2024

CAR-T Cells Combined With Peptide Specific Dendritic Cell in Relapsed/Refractory Leukemia/MDS

A Phase 1 interventional study of Chimeric antigen receptor T cells and peptide specific dendritic cell in Leukemia, Acute Lymphocytic (ALL), Leukemia, Acute Myelogenous (AML) and Myelodysplastic Syndromes, sponsored by Zhujiang Hospital. Recruiting at 1 site in China. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-03-15.

Sponsored by Zhujiang Hospital · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
30
Allocation
Non-randomized
Ages
18 Years to 80 Years
Sex
All
01

Study summary

The main purpose of this study is to verify the safety and potential effectiveness of CART cells combined with peptide specific dendritic cell in relapsed/refractory leukemia.

Read the detailed description

A prospective study to evaluate the safety and efficacy of Chimeric antigen receptor T cells combined with Eps8 or WT1(Wilms tumor 1) peptide specific dendritic cell for patients with relapsed/refractory leukemia. There are options for CAR-targets: CD19, CD20, CD22 and CD10 for acute lymphoblastic leukemia; CD33, CD38 CD56, CD117, CD123, CD34 and Muc1 for acute myeloid leukemia and Myelodysplastic Syndrome. Progression free survival, overall Survival, overall response rate, and duration of response were monitored.

02

Conditions studied

  • Leukemia, Acute Lymphocytic (ALL)
  • Leukemia, Acute Myelogenous (AML)
  • Myelodysplastic Syndromes
03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
30 participants (estimated)

Study arms

  • Experimental
    CAR-T cells combined with peptide specific dendritic cell

    CAR-T cells combined with Eps8 peptide specific dendritic cell,or CAR-T cells combined with WT1 peptide specific dendritic cell

    Biological: Chimeric antigen receptor T cells · Biological: peptide specific dendritic cell

  • Active comparator
    Chimeric antigen receptor T cells

    After pretreatment, chimeric antigen receptor T cells will be transfused.

    Biological: Chimeric antigen receptor T cells

Interventions

  • BiologicalChimeric antigen receptor T cells

    After pretreatment, chimeric antigen receptor T cells will be transfused.

    Also known as: CAR-T

  • Biologicalpeptide specific dendritic cell

    After transfusion of chimeric antigen receptor T cells, Eps8 or WT1 peptide specific dendritic cell were intradermal injected.

    Also known as: WT1 peptide specific dendritic cell, Eps8 peptide specific dendritic cell

05

What researchers measure

Primary outcomes

  1. Occurrence of study related adverse events, according to NCI CTCAE Version 4.0

    Incidence and severity of cytokine release syndrome(CRS): The systemic inflammatory response in patients with significantly increased IL-6 and other cytokines during the observation period is defined as CRS, which is divided into 1-5 grades, 1-2 Grade is mild, grade 3-5 is severe

    Time frame: up to 12 months

Secondary outcomes

  1. Progression free survival time

    Time from random to the first occurrence of disease progression.

    Time frame: 2 years

  2. Overall survival time

    Time from randomization to death due to any cause

    Time frame: 2 years

  3. Overall response rate

    The proportion of the total number of patients with complete remission and partial remission (CR+PR) after treatment in the total number of evaluable cases

    Time frame: 2 years

  4. Duration of response

    During the observation period, the time between complete remission of bone marrow (the ratio of bone marrow blast cells is less than 5%) to the recurrence of bone marrow (the ratio of bone marrow blast cells is greater than 5%) is the continuous remission time.

    Time frame: 2 years

06

Study locations

1 of 1 sites recruiting
  • Zhujiang Hospital, Southern Medical University
    Guangzhou, Guangdong 510282, China
    • Sanfang Tu, M.D, Ph.D · Contact · doctortutu@163.com · 86-20-62782322
    • Yanjie He, M.D, Ph.D · Contact · hyjgzh2006@163.com · 86-20-61643190
    • Yuhua Li, M.D, Ph.D · Principal investigator
    Recruiting
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03291444
Lead sponsor
Zhujiang Hospital
Collaborators
Shenzhen Geno-Immune Medical Institute, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Responsible party
Sponsor
First posted
Sep 25, 2017
Start date
May 5, 2018
Primary completion
Dec 31, 2024 (estimated)
Completion
Jun 1, 2025 (estimated)
Last update
Mar 15, 2024

Study contacts

Sanfang Tu, M.D, Ph.D
Contact
doctortutu@163.com
86-20-62782322
Yanjie He, M.D, Ph.D
Contact
hyjgzh2006@163.com
86-20-61643190
Yuhua Li, M.D, Ph.D
principal investigator · Zhujiang Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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