Primary/Relapsed Acute Lymphoblastic Leukemia (ALL) of Childhood, Adolescents and Young Adults Clinical Trial
Official title:
Prospective Phase I/II Study: Patient-individualized Peptide Vaccination Based on Whole Exome Sequencing With Adjuvant GM-CSF (Granulocyte Macrophage Colony-stimulating Factor) in Children and Young Adults With Primary/Relapsed Acute Lymphoblastic Leukemia
| Verified date | December 2023 |
| Source | University Children's Hospital Tuebingen |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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).
| Status | Completed |
| Enrollment | 30 |
| Est. completion date | December 2023 |
| Est. primary completion date | March 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 1 Year to 30 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Germany | Charite Universitätsmedizin Berlin, Department of Pediatric Oncology/Hematology | Berlin | |
| Germany | University Hospital Düsseldorf, Clinic for Pediatric Oncology, Hematology and Clinical Immunology | Düsseldorf | Nordrhein-Westfalen |
| Germany | University Medical Center for Children and Adolescents Heidelberg | Heidelberg | Baden-Württemberg |
| Germany | University Children's Hospital Munich, Center for Pediatric Hematology and Oncology | München | Bayern |
| Germany | University Children's Hospital Tübingen | Tübingen | Baden-Württemberg |
| Lead Sponsor | Collaborator |
|---|---|
| University Children's Hospital Tuebingen | German Cancer Research Center, Universität Tübingen, University Hospital Tuebingen |
Germany,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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). | Side effects wil be assessed according to NCI common toxicity criteria V4.0. GvHD will be graded according to Glucksberg criteria. A vaccine-specific response will be defined by an at least 2-fold elevated cytokine expression of CD4+ and/or CD8+ T cells over background in response to stimulation with the vaccine peptides. A vaccine-induced response will be defined by an at least 2-fold elevated response at a certain timepoint compared to pre-vaccination. | 120 days | |
| Secondary | To evaluate CD4+ and/or CD8+ T-cell responses over the vaccination period. | T-cell responses will be measured after completion of the study at day 246 and will be analyzed with regard to the T-cell responses at day 120. | 246 days | |
| Secondary | To evaluate changes in minimal residual disease (MRD) during and after treatment. | Possible reduction of MRD levels on days 36, 120 and 246 (after 7, 10 and 16 vaccinations) measured as reduction of 1 log compared to baseline yes/no. | 246 days | |
| Secondary | To evaluate the relapse rate during and after treatment. | Relapse rates will be assessed on days 120 and 246. | 246 days | |
| Secondary | To evaluate the event-free survival (EFS) during and after treatment. | EFS will be assessed on days 120 and 246. | 246 days |