Clinical Study of DC-AML Cells in the Treatment of Acute Myeloid Leukemia

August 16, 2021 updated by: Affiliated Hospital to Academy of Military Medical Sciences

Safety and Feasibility Study of Dendritic Cell (DC) Vaccination Expressing WT1/hTERT/Survivin in AML Patients With Minimal Residual Disease (MRD)

The primary aim of this innovative immunotherapy using WT1/hTERT/Survivin-loaded DCs is to determine whether this novel DC vaccination is safe and can significantly prevent clinical relapse and increase survival of acute myeloid leukemia (AML) patients by eradicating minimal residual disease, while maintaining its safety profile in this phase I trial.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

we will conduct a single-arm phase I clinical study in 20 patients with acute myeloid leukemia (AML) at the stage of minimal residual disease (MRD) following standard chemotherapy, and these patients are not the subjects of stem cell transplantation. Adult patients between18 and 70 years old with AML who have entered morphological remission after induction, consolidation or intensive chemotherapy with molecular signature of increased WT1 molecule levels and pathological characteristics of bone marrow biopsy, together with fulfilling all other eligibility criteria, will be vaccinated with dendritic cells loaded with tri-antigens (WT1/TERT/survivin) in the absence of any additional therapeutic measurements. The primary aim of this innovative immunotherapy study is to determine whether the anti-leukemic effects seen in our preclinical study can be confirmed in patients and whether such DC vaccination can significantly prevent relapse and increase survival of AML patients by eradicating minimal residual disease. Patients will be recruited at 307 Hospital in Beijing. Recruitment will start in the second half of 2021 and will last for two years or until 20 safety and efficacy-evaluable AML patients are included. This is a single-arm trial. The patients who present MRD after complete chemotherapy will receive a conditioning regimen of cyclophosphamide, followed by six infusions of autologous or HLA-matched donor-derived DCs loaded with tri-antigens including WT1/TERT/survivin. The dendritic cell therapy product will be administered in the stem cell transplantation center at 307 Hospital headed by Dr. Liang-Ding Hu. After inclusion of 20 safety/feasibility-evaluable patients, relapse rate, relapse-free survival and overall survival analysis will be performed. Tumor marker levels and immune signature molecules will also be monitored at molecular and immunological levels, and general and disease-specific quality of life will be evaluated using quality of life questionnaires at various time points.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Sun Yao, M.D.,Ph.D.
  • Phone Number: 010-66947402
  • Email: suny320@126.com

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100071
        • Recruiting
        • Department of Hematology
        • Contact:
          • Sun Yao, M.D.,Ph.D.
          • Phone Number: +86-010-6694-7402
          • Email: suny320@126.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of acute myeloid leukemia (AML) according to the 2008 criteria of the World Health Organization (WHO).
  • Patients completed induction and consolidation chemotherapy and have achieved complete remission (CR) by bone marrow biopsy criteria but with persistent MRD (defined by upregulated WT1 level and less than 5% of blast cells in bone marrow biopsy) and are not eligible for stem cell transplant
  • Patients have MRD molecular relapse (defined by upregulated WT1 level and less than 5% of blast cells in bone marrow biopsy) after achieved CR following induction and consolidation chemotherapy.
  • Patients with molecular relapse (define by upregulated WT1 level and less than 5% of blast cells in bone marrow biopsy) after allogeneic stem cell transplant
  • Leukemic cells express at least one of the following antigens: WT1, hTERT or survivin detected by qRT-PCR and/or flow cytometry or immunohistochemistry
  • Karnofsky PS ≥60% or ECOG PS≤2.

  • Patients must have organ and marrow function as defined below:

    • leukocytes >=3,000/mcL
    • absolute neutrophil count >=1,500/mcL
    • platelets >=100,000/mcL
    • hemoglobin >=9.0 g/dL
    • total bilirubin within normal institutional limits except in patients with Gilberts Syndrome who must have a total bilirubin < 3.0 mg/dL
    • AST(SGOT)/ALT(SGPT) Serum ALT/AST < 2.5X ULN
    • creatinine clearance Calculated creatinine clearance (CrCl) >=50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation)
    • Adequate cardiac function: LVEF ≥50% by MUGA
  • Ability of subject to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Participation in any other interventional clinical trial during the study period.
  • History or concomitant presence of any other malignancy, except for any other effectively treated malignancy that has been in remission for >5 years or that is highly likely to be cured at the time of enrollment.
  • Patients with a second invasive malignancy requiring treatment within the last 2 years are not eligible.
  • Patients with any form of systemic immunodeficiency, including AIDS or primary immunodeficiency such as Severe Combined Immunodeficiency Disease, are ineligible. The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the treatment.
  • Active hepatitis B, C infection
  • Patients on immunosuppressive drugs including corticosteroids.
  • Patients with autoimmune diseases such as Crohn s disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus erythematosus.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations at the time of treatment that would limit compliance with study requirements.
  • Allergic to human albumin or IL-2. History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study.
  • Pregnant or breast-feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DC vaccine
Vaccination with autologous or HLA-matched donors' WT1/TERT/survivin loaded DCs plus follow-up care.
Biological: DC vaccine
Autologous/or HLA-matched donors' DCs loaded with WT1/TERT/survivin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the Incidence of Treatment Adverse Events
Time Frame: through study completion,an average of 3 years
To determine the safety of autologous/or HLA-matched DCs loaded with WT1/TERT/Survivin. The primary objective of this single-arm phase I clinical study is to determine the safety and feasibility of WT1/TERT/survivin-targeted DC vaccination in adult AML patients with MRD at very high risk of relapse.
through study completion,an average of 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OS
Time Frame: through study completion,an average of 3 years
Overall survival
through study completion,an average of 3 years
Complete MRD response rate
Time Frame: through study completion,an average of 3 years
To determine the Complete MRD response rate
through study completion,an average of 3 years
Relapse rate
Time Frame: through study completion,an average of 3 years
(time frame: at study completion, an average of 5 year)
through study completion,an average of 3 years
Relapse-free survival
Time Frame: through study completion,an average of 3 years
(time frame: at study completion, an average of 5 year)
through study completion,an average of 3 years
Change in WT1 mRNA levels from peripheral blood samples and/or bone marrow biopsy samples.
Time Frame: through study completion,an average of 3 years
Efficacy assessment will also be performed on a molecular level. Bone marrow biopsy samples obtained from participants will be examined, and part of samples will be analyzed by qRT-PCR for WT1 expression.
through study completion,an average of 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Affiliated Hospital to Academy of Military Medical Sciences

Investigators

  • Study Director: Liangding Hu, M.D., the Fifth Medical Center the PLA General Hospital
  • Principal Investigator: Liangding Hu, M.D., the Fifth Medical Center the PLA General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2021

Primary Completion (Anticipated)

July 1, 2026

Study Completion (Anticipated)

July 1, 2026

Study Registration Dates

First Submitted

July 13, 2021

First Submitted That Met QC Criteria

August 3, 2021

First Posted (Actual)

August 11, 2021

Study Record Updates

Last Update Posted (Actual)

August 20, 2021

Last Update Submitted That Met QC Criteria

August 16, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 307-DC-1911

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Myeloid Leukemia

Clinical Trials on DC vaccine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovakia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe