B Cell Precursor Acute Lymphoblastic Leukemia With Mixed Chimerism or Minimal Residual Disease After Allogeneic Stem Cell TransplantationPhase 2DLI-TARGETNCT03982992
Allogeneic Donor Lymphocyte Infusions Combined With Blinatumomab
A Phase 2 study testing Blinatumomab in combination with donor lymphocyte infusion in people with B Cell Precursor Acute Lymphoblastic Leukemia With Mixed Chimerism or Minimal Residual Disease After Allogeneic Stem Cell Transplantation and B-Cell Acute Lymphoblastic Leukemia, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.
Trial summary
This phase 2 study is designed to evaluate the safety, tolerability and efficacy of allogeneic donor lymphocyte infusions (DLI) combined with the bispecific T cell engager blinatumomab in B-precursor ALL patients who have mixed chimerism (MC) or are MRD-positive after allogeneic SCT and are refractory to at least one… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B Cell Precursor Acute Lymphoblastic Leukemia With Mixed Chimerism or Minimal Residual Disease After Allogeneic Stem Cell Transplantation, B-Cell Acute Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia
- What is being tested?
- Blinatumomab in combination with donor lymphocyte infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jun 2019to 30 Nov 2021
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients with CD19+ B-precursor ALL (as determined by immunophenotyping) in hCR (defined as having less than 5% blasts in bone marrow) after allogeneic SCT.
- One, or a combination of the following documented after an interval of at least 2 weeks since cessation of the most recent leukemia-targeting therapy (i.e. chemotherapy, immunotherapy or cellular therapy, except for intrathecal prophylaxis):
- Positivity for CD19+ MRD (molecular failure or molecular relapse), defined as presence of MRD at a level of ≥10^-4 according to an assay with a minimum sensitivity of 10^-4.
- Donor chimerism <90%, as determined by analysis of host and donor STRs in bone marrow sample engraftment analysis.
- At least one previous line of treatment for MRD-positivity and/or reduced donor chimerism (i.e. blinatumomab, DLI, TKI or other agents) after allogeneic SCT.
- For those with BCR/ABL-positive B-precursor ALL only: persistence of MRD and/or MC following at least one ≥ second generation TKI (dasatinib, nilotinib, bosutinib, ponatinib) OR intolerance to second generation TKI and intolerance to or persistence of MRD and/or MC following imatinib mesylate.
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- Availability of allogeneic donor lymphocytes from the subject's donor (at least 2 x 10^8 T cells/kg).
- Subject has provided written informed consent prior to initiation of any study-specific activities/procedures.
- Subject has provided informed consent to be followed up in the GMALL-Registry.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
- Renal function as follows: serum creatinine < 2.0 mg/dL and estimated glomerular filtration rate > 30 mL/min.
- Hepatic function as follows:
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3.0 x upper limit of normal (ULN)
- Alkaline phosphatase (ALP) < 3.0 x ULN
- Bilirubin ≤ 2.0 x ULN (unless considered due to Gilbert's syndrome or hemolysis)
- For female subjects only: Women of child-bearing age have to use a reliable method of contraception.
Who cannot join
- Eligibility for treatment with blinatumomab ALONE or other antibody-based treatment approaches (e.g. inotuzumab ozogamicin), as considered by the treating physician.
- Eligibility for standard chemotherapy, as considered by the treating physician.
- Antitumor therapy (chemotherapy, antibody therapy, molecular-targeted therapy, retinoid therapy, or investigational agent) within 14 days or 5 half-lives (whichever is longer) prior to baseline MRD and/or chimerism assessment.
- Treatment with systemic immune modulators including, but not limited to, non-topical systemic corticosteroids, cyclosporine, and tacrolimus within 2 weeks before enrollment.
- Any grade of GvHD currently requiring treatment.
- Clinically relevant central nervous system (CNS) pathology requiring treatment (e.g., unstable epilepsy).
- Evidence of current CNS involvement by ALL.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 2 Study Evaluating the Safety, Tolerability and Efficacy of Allogeneic Donor Lymphocyte Infusions Combined With Blinatumomab in Patients With Treatment-Resistant Mixed Chimerism or Minimal Residual Disease of B-precursor Acute Lymphoblastic Leukemia After Allogeneic Stem Cell Transplantation
This phase 2 study is designed to evaluate the safety, tolerability and efficacy of allogeneic donor lymphocyte infusions (DLI) combined with the bispecific T cell engager blinatumomab in B-precursor ALL patients who have mixed chimerism (MC) or are MRD-positive after allogeneic SCT and are refractory to at least one MRD- or MC-targeted therapy (i.e. blinatumomab, DLI, tyrosine kinase inhibitors or other agents).
- Conditions
- B Cell Precursor Acute Lymphoblastic Leukemia With Mixed Chimerism or Minimal Residual Disease After Allogeneic Stem Cell Transplantation, B-Cell Acute Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia in Remission, Acute Lymphoblastic Leukemia, Adult
- Being tested
- Blinatumomab in combination with donor lymphocyte infusion
- Keywords
- donor lymphocyte infusion, blinatumomab, combinatorial, minimal residual disease, MRD, mixed chimerism, MC, DLI-TARGET, acute lymphoblastic leukemia
- Medical subject headings
- Burkitt Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blinatumomab in combination with donor lymphocyte infusionDrug
Continuous blinatumomab infusion in combination with allogeneic donor lymphocyte infusion
| Study group | Role | What they receive |
|---|---|---|
| DLI-TARGET | Experimental | 14d screening period: methotrexate, cytarabine, dexamethasone infusion i.th.
Cycle 1 (all patients): d1-28: blinatumomab continuous infusion i.v., d4: allogeneic donor lymphocyte single infusion i.v., d29: methotrexate, cytarabine, dexamethasone infusion i.th.
Cycle 2 (only patients with toxicity ≤ grade 2 CTCAE in cycle 1): d43-d70: blinatumomab continuous infusion i.v., d46: allogeneic donor lymphocyte single infusion i.v., d71: methotrexate, cytarabine, dexamethasone infusion i.th. Receives: Drug: Blinatumomab in combination with donor lymphocyte infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of combined DLI and blinatumomab treatment in subjects with treatment-resistant MC or MRD of CD19+ B-precursor ALL after allogeneic SCT
Subject incidence and grade of adverse events (AEs) including graft-versus-host disease (GvHD). The intensity of (S)AEs will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.
Measured: 18 weeks
Secondary outcomes (2)
Efficacy of a combined treatment of DLI and blinatumomab to induce a complete MRD/chimerism response
MRD response based on RT-PCR: Complete MRD response (MolCR): hCR and MRD not detectable by molecular probe[s] with a sensitivity ≥10-4. The MRD response is calculated as: [number of patients achieving complete MRD response after at least one cycle (minimum 4 days blinatumomab) of study treatment] / [number of patients who received at least 1 cycle (minimum 4 days blinatumomab) of study treatment].
Mixed chimerism response: CC response: only donor STRs in bone marrow; Low-level MC response ≥90% but <100% donor STRs in bone marrow. The MC response is calculated as: [number of patients achieving CC/low-level MC response after at least one cycle (minimum 4 days blinatumomab) of study treatment] / [number of patients who received at least 1 cycle (minimum 4 days blinatumomab) of study treatment].
Measured: 18 weeks
Duration of the response and survival after combined treatment of DLI and blinatumomab
For patients who received at least one cycle (minimum 4 days of blinatumomab), progression-free survival and overall survival will be calculated using kaplan-meier survival estimates. Descriptive summary statistics (N, mean, standard deviation, minimum, median and maximum) for the duration of response will be performed for all patients with an observed complete MRD response or CC/low-level MC response.
Measured: 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2019
- Study start1 Jun 2019
- Primary completion31 May 2021
- Study completion30 Nov 2021
Why it stopped: Lack of potential study subjects due to a change of standard of care treatment outside of clinical trials.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B Cell Precursor Acute Lymphoblastic Leukemia With Mixed Chimerism or Minimal Residual Disease After Allogeneic Stem Cell TransplantationStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig-Maximilians - University of Munich
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Principal investigator, Christian Schmidt, MD, Ludwig-Maximilians - University of Munich
- Investigators
- Marion Subklewe, MD, Principal investigator, LMU KlinikumChristian Schmidt, MD, Principal investigator, LMU KlinikumSascha Haubner, MD, Principal investigator, LMU Klinikum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03982992
- Sponsor's protocol ID
- 2017-002314-31
- Other IDs
- 2017
- Acronym
- DLI-TARGET
- Status last verified
- Mar 2024
- First submitted
- 3 Jun 2019
- Last updated
- 12 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study Evaluating the Safety, Tolerability and Efficacy of Allogeneic Donor Lymphocyte Infusions Combined With Blinatumomab in Patients With Treatment-Resistant Mixed Chimerism or Minimal Residual Disease of B-precursor Acute Lymphoblastic Leukemia After Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT03982992
- Acronym / sponsor ID
- DLI-TARGET / 2017-002314-31
- Conditions
- B Cell Precursor Acute Lymphoblastic Leukemia With Mixed Chimerism or Minimal Residual Disease After Allogeneic Stem Cell Transplantation, B-Cell Acute Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia in Remission, Acute Lymphoblastic Leukemia, Adult
- Keywords
- donor lymphocyte infusion, blinatumomab, combinatorial, minimal residual disease, MRD, mixed chimerism, MC, DLI-TARGET
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of potential study subjects due to a change of standard of care treatment outside of clinical trials.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ludwig-Maximilians - University of MunichUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 1 Jun 2019 (actual)
- Primary completion
- 31 May 2021 (actual)
- Study completion
- 30 Nov 2021 (actual)
- First posted
- 12 Jun 2019 (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.
This phase 2 study is designed to evaluate the safety, tolerability and efficacy of allogeneic donor lymphocyte infusions (DLI) combined with the bispecific T cell engager blinatumomab in B-precursor ALL patients who have mixed chimerism (MC) or are MRD-positive after allogeneic SCT and are refractory to at least one MRD- or MC-targeted therapy (i.e. blinatumomab, DLI, tyrosine kinase inhibitors or other agents).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DLI-TARGET | Experimental | Drug: Blinatumomab in combination with donor lymphocyte infusion14d screening period: methotrexate, cytarabine, dexamethasone infusion i.th. Cycle 1 (all patients): d1-28: blinatumomab continuous infusion i.v., d4: allogeneic donor lymphocyte single infusion i.v., d29: methotrexate, cytarabine, dexamethasone infusion i.th. Cycle 2 (only patients with toxicity ≤ grade 2 CTCAE in cycle 1): d43-d70: blinatumomab continuous infusion i.v., d46: allogeneic donor lymphocyte single infusion i.v., d71: methotrexate, cytarabine, dexamethasone infusion i.th. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Adult patients with CD19+ B-precursor ALL (as determined by immunophenotyping) in hCR (defined as having less than 5% blasts in bone marrow) after allogeneic SCT.
- One, or a combination of the following documented after an interval of at least 2 weeks since cessation of the most recent leukemia-targeting therapy (i.e. chemotherapy, immunotherapy or cellular therapy, except for intrathecal prophylaxis):
- At least one previous line of treatment for MRD-positivity and/or reduced donor chimerism (i.e. blinatumomab, DLI, TKI or other agents) after allogeneic SCT.
- For those with BCR/ABL-positive B-precursor ALL only: persistence of MRD and/or MC following at least one ≥ second generation TKI (dasatinib, nilotinib, bosutinib, ponatinib) OR intolerance to second generation TKI and intolerance to or persistence of MRD and/or MC following imatinib mesylate.
- Availability of allogeneic donor lymphocytes from the subject's donor (at least 2 x 10^8 T cells/kg).
Key exclusion criteria (7 listed)
- Eligibility for treatment with blinatumomab ALONE or other antibody-based treatment approaches (e.g. inotuzumab ozogamicin), as considered by the treating physician.
- Eligibility for standard chemotherapy, as considered by the treating physician.
- Antitumor therapy (chemotherapy, antibody therapy, molecular-targeted therapy, retinoid therapy, or investigational agent) within 14 days or 5 half-lives (whichever is longer) prior to baseline MRD and/or chimerism assessment.
- Treatment with systemic immune modulators including, but not limited to, non-topical systemic corticosteroids, cyclosporine, and tacrolimus within 2 weeks before enrollment.
- Any grade of GvHD currently requiring treatment.
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 |
|---|---|---|
| Blinatumomab in combination with donor lymphocyte infusionContinuous blinatumomab infusion in combination with allogeneic donor lymphocyte infusion | Drug | DLI-TARGET |
Primary outcome
Safety and tolerability of combined DLI and blinatumomab treatment in subjects with treatment-resistant MC or MRD of CD19+ B-precursor ALL after allogeneic SCT
Time frame: 18 weeks
Subject incidence and grade of adverse events (AEs) including graft-versus-host disease (GvHD). The intensity of (S)AEs will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.
2 secondary outcomes
Efficacy of a combined treatment of DLI and blinatumomab to induce a complete MRD/chimerism response
Time frame: 18 weeks
Duration of the response and survival after combined treatment of DLI and blinatumomab
Time frame: 18 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2024.
- Individual participant dataSharing planned: Undecided
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.
Marion Subklewe, MD principal investigator
LMU Klinikum
Christian Schmidt, MD principal investigator
LMU Klinikum
Sascha Haubner, MD principal investigator
LMU Klinikum
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Blinatumomab in combination with donor lymphocyte infusion in people with B Cell Precursor Acute Lymphoblastic Leukemia With Mixed Chimerism or Minimal Residual Disease After Allogeneic Stem Cell Transplantation and B-Cell Acute Lymphoblastic Leukemia, run by Ludwig-Maximilians - University of Munich at 1 site 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 16 inclusion and 7 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: withdrawn, as of the sponsor's last update on 12 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 phase mean?
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 was withdrawn before enrolling participants, so there are no results.
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?
Safety and tolerability of combined DLI and blinatumomab treatment in subjects with treatment-resistant MC or MRD of CD19+ B-precursor ALL after allogeneic SCT (time frame: 18 weeks). 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 12 Mar 2024.