CompletedPhase 1/2

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

Germany30 participantsStarted 2016-06

Plain-language 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).

Who can participate

Age range1 Year – 30 Years

SexALL

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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.

What they're measuring

Primary endpoint is "success of treatment" defined as a patient showing a vaccination-induced T-cell response without unacceptable toxicity and acute GvHD of Grade III or higher or extensive chronic GvHD until day 120 (after 10 vaccinations).

Timeframe: 120 days

Trial details

NCT IDNCT03559413

SponsorUniversity Children's Hospital Tuebingen

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2022-03