Vaccination against childhood leukemia

Prospective phase I/II study: Patient-individualized peptide vaccination based on whole exome sequencing with adjuvant GM-CSF in children with relapsed acute lymphoblastic leukemia

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2015-005281-29-DE

Enrollment

Registered

2016-01-15

Start date

2016-06-07

Completion date

Unknown

Last updated

2025-02-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Relapsed acute lymphatic leukemia MedDRA version: 18.1 Level: LLT Classification code 10000842 Term: Acute lymphatic leukaemia System Organ Class: 100000004864 MedDRA version: 18.1 Level: LLT Classification code 10054444 Term: Leukemia relapse System Organ Class: 100000004864

Interventions

Product Name: Individualized peptides Pharmaceutical Form: Solution for injection Trade Name: Sargramostim Product Name: Sargramostim Pharmaceutical Form: Solution for injection

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • pediatric patients with ALL (T, B, pro-B, pre-B or c-ALL) = CR3 or with = 1st relapse after stem cell transplantation (SCT); hematological remission has to be reached (=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: Subjects presenting with any of the following criteria will not be included in the trial: • Frank relapse (>5% leukemic blasts) • Ejection fraction 4 mg/dL and elevation of transaminases higher than 400 U/L • Severe infection (HIV, Chronic active viral hepatitis) • Significant psychiatric disabilities, uncontrolled seizure disorders or severe peripheral neuropathy/ leukencephalopathy. • Acute GvHD grade III or IV or extensive chronic GvHD. • Signs of autoimmune disease (i.e. idiopathic thrombocytopenic purpura, autoimmune haemolytic anemia) • Need for immunosuppressive drugs • Concurrent severe or uncontrolled medical disease which by assessment of the treating physician could compromise participation in the study • Women during pregnancy and lactation. • History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product. • Participation in other clinical trials or observation period of competing trials. • No leukemic blasts available for DNA extraction and cryopreservation requirements. • Females of childbearing potential (FCBP1) that do not agree ? to utilize two reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including dose interruptions), and for at least 28 days after study treatment discontinuation and must agree to regular pregnancy testing during this timeframe • Males that do not agree ? to use a latex condom during any sexual contact with FCBP while participating in the study and for 28 days following discontinuation from this study, even if he has undergone a successful vasectomy ? to refrain from donating semen or sperm while on and for 28 days after discontinuation from this study treatment. • Subjects that do not agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment. • All subjects that do not agree not to share medication.

Design outcomes

Primary

Measure	Time frame
Main Objective: Primary objective is 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. Primary endpoint is "success of treatment" 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 1.unacceptable toxicities (grade 4 according to NCI-CTC) 2.acute GvHD = Grade III or extensive chronic GvHD and in whom 3.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 Objective: 1.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. 2.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). 3.To evaluate the relapse rate on days 99 and 246 (after 15 and 36 weeks). 4.To evaluate the Event free survival (EFS) on days 99 and 246 (after 15 and 36 weeks). ;Primary end point(s): Primary endpoint is "success of treatment" defined as a patient without unacceptable toxicity and acute GvHD ? grade III or extensive chronic GvHD and showing a vaccination-induced T-cell response. Thus, a composite variable is used as primary endpoint: Treatment success is defined as a patient without 1.unacceptable toxicities (grade 4 according to NCI-CTC) 2.acute GvHD = grade III or extensive chronic GvHD	—

Measure

Time frame

Main Objective: Primary objective is 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. Primary endpoint is "success of treatment" 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 1.unacceptable toxicities (grade 4 according to NCI-CTC) 2.acute GvHD = Grade III or extensive chronic GvHD and in whom 3.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 Objective: 1.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. 2.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). 3.To evaluate the relapse rate on days 99 and 246 (after 15 and 36 weeks). 4.To evaluate the Event free survival (EFS) on days 99 and 246 (after 15 and 36 weeks). ;Primary end point(s): Primary endpoint is "success of treatment" defined as a patient without unacceptable toxicity and acute GvHD ? grade III or extensive chronic GvHD and showing a vaccination-induced T-cell response. Thus, a composite variable is used as primary endpoint: Treatment success is defined as a patient without 1.unacceptable toxicities (grade 4 according to NCI-CTC) 2.acute GvHD = grade III or extensive chronic GvHD

—

Secondary

Measure	Time frame
Secondary end point(s): 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. The amount of CD8+ and CD4+ T-cell response at week 36 will be evaluated and compared to week 18 using a paired t-test. The amount at all time points documented will be displayed graphically. 2. 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). A reduction of 1 log will be considered clinically relevant and the endpoint is defined as reduction of 1 log yes / no. The percentage of successful reductions at several time points over the study (36d, 120d and 246d) will be displayed graphically. 3. To evaluate the relapse rate on days120 and 246 (after 18 and 36 weeks). Relapse rate will be analyzed using Kaplan-Meier-Methods 4. To evaluate the Event free survival (EFS) on days 120 and 246 (after 18 and 36 weeks). Event free survival will be analyzed using Kaplan-Meier-Methods The analysis results of all secondary endpoints are regarded as being descriptive. ;Timepoint(s) of evaluation of this end point: d 36, 120 and 246	—

Measure

Time frame

Secondary end point(s): 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. The amount of CD8+ and CD4+ T-cell response at week 36 will be evaluated and compared to week 18 using a paired t-test. The amount at all time points documented will be displayed graphically. 2. 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). A reduction of 1 log will be considered clinically relevant and the endpoint is defined as reduction of 1 log yes / no. The percentage of successful reductions at several time points over the study (36d, 120d and 246d) will be displayed graphically. 3. To evaluate the relapse rate on days120 and 246 (after 18 and 36 weeks). Relapse rate will be analyzed using Kaplan-Meier-Methods 4. To evaluate the Event free survival (EFS) on days 120 and 246 (after 18 and 36 weeks). Event free survival will be analyzed using Kaplan-Meier-Methods The analysis results of all secondary endpoints are regarded as being descriptive. ;Timepoint(s) of evaluation of this end point: d 36, 120 and 246

—

Countries

Germany

Contacts

Public ContactCenter for clinical studies

Children's University Hospital

+4970712984711

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026