IVAC-ALL-1

Primary objectives

• To evaluate the safety, clinical toxicity and in vivo immunological effects of a patient-individualized peptide vaccination in pediatric patients with acute lymphoblastic leukemia who experienced ≥2nd relapse or ≥1st relapse after previous stem cell transplantation.

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

Therefore, a composite variable is used as primary endpoint: Treatment success is defined as a patient without:

• unacceptable toxicities (grade 4 according to NCI-CTC)
• acute GvHD ≥Grade III or extensive chronic GvHD and in whom
• a vaccine-specific response of CD4+ and/or CD8+ T-cells could be induced

The primary endpoint will be measured at day 120 after 10 vaccinations were administered.

Secondary objectives

• To evaluate CD8+ or CD4+ T-cell response over the vaccination period measured after completion of the study (16 vaccinations, week 36) and to analyze this with regard to the T-cell response at day 120.
• To evaluate changes in minimal residual disease during and after treatment (possible reduction of minimal residual disease (MRD) levels on day 36, 120 and 246 (after 6, 18 and 36 weeks and after 7, 10 and 16 vaccinations, respectively).
• To evaluate the relapse rate on days 99 and 246 (after 15 and 36 weeks).
• To evaluate the Event free survival (EFS) on days 99 and 246 (after 15 and 36 weeks).

16 vaccinations (subcutane) during 36 weeks with an individualized vaccine

• Pediatric patients with ALL (T, B, pro-B, pre-B or c-ALL) ≥CR2 or with ≥1st relapse after stem cell transplantation (SCT); 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
• Age 1-18 years
• Informed consent must be given by legal representatives

• Open relapse (>5% leukemic blasts)
• Age < 1 year
• Ejection fraction <25%; Creatinine-clearance <40ml/min; Bilirubine >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/ leukencephalopathy
• Signs of autoimmune disease (i.e. idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia)
• Need for immunosuppressive drugs
• Special populations: pediatric patients (age 1-18 years)