Patient-individualized Peptide Vaccination Based on Tumor-specific Mutations in Children and Young Adults With Primary/Relapsed ALL

NCT ID: NCT03559413

Last Updated: 2023-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2023-12-31

Brief Summary

The aim of this clinical study is to evaluate the feasibility and safety of an individualized peptide vaccination approach in patients with acute lymphoblastic leukemia (ALL). For this purpose, tumor-specific mutations are analyzed by comparative exome sequencing of tumor and healthy reference tissue. Expression of variants is further validated by RNA sequencing. In a second step, HLA-binding (human leukocyte antigen-binding) peptides derived from mutated protein sequences are selected for vaccination. The peptides are administered as a vaccination cocktail with adjuvant GM-CSF and Imiquimod over a course of 9 months and a total of 16 vaccinations. Primary objective is the de novo induction of a specific T cell response without unacceptable toxicity and acute GvHD (graft versus host disease).

Conditions

Primary/Relapsed Acute Lymphoblastic Leukemia (ALL) of Childhood, Adolescents and Young Adults

Keywords

Individualized peptide vaccination; Immunotherapy; Tumor-specific mutations; Neoantigens

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention group

Group Type: EXPERIMENTAL

Individual peptide vaccination with adjuvant GM-CSF and Imiquimod

Intervention Type: BIOLOGICAL

Intradermal injection of a cocktail of 3-5 individual HLA-binding peptides. Subcutaneous injection of adjuvant GM-CSF at vaccination site. Topical administration of Imiquimod at vaccination site.

Interventions

Individual peptide vaccination with adjuvant GM-CSF and Imiquimod

Intradermal injection of a cocktail of 3-5 individual HLA-binding peptides. Subcutaneous injection of adjuvant GM-CSF at vaccination site. Topical administration of Imiquimod at vaccination site.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Pediatric patients and young adults with ALL (T, B, pro-B, pre-B or c-ALL) ≥CR3 or with ≥1st relapse after stem cell transplantation (SCT); or patients in ≤CR2 who have received SCT without having reached a sufficient molecular remission prior to, or after SCT (defined as MRD ≥10^-4); or patients with initially refractory disease to standard treatment who could proceed to stem cell transplantation with alternative treatment options.
• Hematological remission has to be reached (<5% blasts in bone marrow or detectable minimal residual disease (MRD) ≤5x10^-2) after salvage chemotherapy and/or subsequent SCT.

Exclusion Criteria

• Frank relapse (>5% leukemic blasts).
• Ejection fraction <25%; Creatinine-clearance <40ml/min; Bilirubin >4mg/dl, Transaminases >400 units/ml; severe infection (HIV, Hepatitis), acute GvHD III-IV or chronic GvHD.
• Significant psychiatric disabilities, uncontrolled seizure disorders or severe peripheral neuropathy/ leukoencephalopathy.
• Signs of autoimmune disease (i.e. idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia).
• Need for immunosuppressive drugs.
• No tumor material available for exome sequencing.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Cancer Research Center

OTHER

Sponsor Role: collaborator

Universität Tübingen

OTHER

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: collaborator

University Children's Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Peter Lang

Prof. Dr. med.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter Lang, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Children's Hospital Tuebingen

Locations

University Medical Center for Children and Adolescents Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

University Children's Hospital Tübingen

Tübingen, Baden-Wurttemberg, Germany

University Children's Hospital Munich, Center for Pediatric Hematology and Oncology

München, Bavaria, Germany

University Hospital Düsseldorf, Clinic for Pediatric Oncology, Hematology and Clinical Immunology

Düsseldorf, North Rhine-Westphalia, Germany

Charite Universitätsmedizin Berlin, Department of Pediatric Oncology/Hematology

Berlin, , Germany

Countries

Germany

Other Identifiers

2015-005281-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IVAC-ALL-1

Identifier Type: -

Identifier Source: org_study_id