Primary/Relapsed Acute Lymphoblastic Leukemia (ALL) of Childhood, Adolescents and Young AdultsPhase 1/2NCT03559413
Patient-individualized Peptide Vaccination Based on Tumor-specific Mutations in Children and Young Adults With Primary/Relapsed ALL
A Phase 1/2 study testing Individual peptide vaccination with adjuvant GM-CSF and Imiquimod in people with Primary/Relapsed Acute Lymphoblastic Leukemia (ALL) of Childhood, Adolescents and Young Adults, run by University Children's Hospital Tuebingen at 5 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 30 years
- Conditions the study is for
- Primary/Relapsed Acute Lymphoblastic Leukemia (ALL) of Childhood, Adolescents and Young Adults
- What is being tested?
- Individual peptide vaccination with adjuvant GM-CSF and Imiquimod
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 5 sitesGermany
- Study dates
- Jun 2016to Dec 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Germany5 sites
Charite Universitätsmedizin Berlin, Department of Pediatric Oncology/Hematology
Berlin, 13353
University Hospital Düsseldorf, Clinic for Pediatric Oncology, Hematology and Clinical Immunology
Düsseldorf, North Rhine-Westphalia, 40225
University Medical Center for Children and Adolescents Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
University Children's Hospital Munich, Center for Pediatric Hematology and Oncology
München, Bavaria, 80337
University Children's Hospital Tübingen
Tübingen, Baden-Wurttemberg, 72076
About this study
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
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
- Being tested
- Individual peptide vaccination with adjuvant GM-CSF and Imiquimod
- Keywords
- Individualized peptide vaccination, Immunotherapy, Tumor-specific mutations, Neoantigens
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Individual peptide vaccination with adjuvant GM-CSF and ImiquimodBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Not described Receives: Biological: Individual peptide vaccination with adjuvant GM-CSF and Imiquimod |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 120 days
Secondary outcomes (4)
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.
Measured: 246 days
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.
Measured: 246 days
To evaluate the relapse rate during and after treatment.
Relapse rates will be assessed on days 120 and 246.
Measured: 246 days
To evaluate the event-free survival (EFS) during and after treatment.
EFS will be assessed on days 120 and 246.
Measured: 246 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2018
- Study startJun 2016
- Primary completionMar 2022
- Study completionDec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary/Relapsed Acute Lymphoblastic Leukemia (ALL) of Childhood, Adolescents and Young AdultsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Children's Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Collaborators
- German Cancer Research Center, Universität Tübingen, University Hospital Tuebingen
- Responsible party
- Principal investigator, Peter Lang, University Children's Hospital Tuebingen
- Investigators
- Peter Lang, Prof. Dr., Principal investigator, University Children's Hospital Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03559413
- Sponsor's protocol ID
- IVAC-ALL-1
- Other IDs
- 2015-005281-29, 2015
- Status last verified
- Dec 2023
- First submitted
- 13 Jun 2018
- Last updated
- 4 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all IPD that underlie results in a publication
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03559413
- Acronym / sponsor ID
- IVAC-ALL-1
- Conditions
- Primary/Relapsed Acute Lymphoblastic Leukemia (ALL) of Childhood, Adolescents and Young Adults
- Keywords
- Individualized peptide vaccination, Immunotherapy, Tumor-specific mutations, Neoantigens
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University Children's Hospital TuebingenUniversity, hospital or other
- Collaborators
- German Cancer Research Center, Universität Tübingen, University Hospital Tuebingen
- Study start
- Jun 2016 (actual)
- Primary completion
- Mar 2022 (actual)
- Study completion
- Dec 2023 (actual)
- First posted
- 18 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Biological: Individual peptide vaccination with adjuvant GM-CSF and Imiquimod |
Who may qualify
- Ages
- 1 year to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Individual peptide vaccination with adjuvant GM-CSF and ImiquimodIntradermal 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. | Biological | Intervention group |
Primary outcome
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).
Time frame: 120 days
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.
4 secondary outcomes
To evaluate CD4+ and/or CD8+ T-cell responses over the vaccination period.
Time frame: 246 days
To evaluate changes in minimal residual disease (MRD) during and after treatment.
Time frame: 246 days
To evaluate the relapse rate during and after treatment.
Time frame: 246 days
To evaluate the event-free survival (EFS) during and after treatment.
Time frame: 246 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2023.
- Individual participant dataSharing planned: Yes. all IPD that underlie results in a publication
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Lang, Prof. Dr. principal investigator
University Children's Hospital Tuebingen
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Individual peptide vaccination with adjuvant GM-CSF and Imiquimod in people with Primary/Relapsed Acute Lymphoblastic Leukemia (ALL) of Childhood, Adolescents and Young Adults, run by University Children's Hospital Tuebingen at 5 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). (time frame: 120 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2023.