Donor Lymphocyte InfusionPhase 2NCT03771222
Prophylactic Donor Lymphocyte Infusion After Allo-PBSCT for Patients With Very High-risk Hematologic Malignancies
A Phase 2 study testing Prophylactic DLI in people with Donor Lymphocyte Infusion and Peripheral Blood Stem Cell Transplantation, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
Unmanipulated allogenic peripheral blood stem cell transplantation (allo-PBSCT) has been an established treatment to cure high-risk leukemia/lymphoma. Relapse is the main cause of treatment failure for patients with relapsed/refractory disease or with very high-risk gene mutations such as TP53, TET2 and DNMT3a. Read more about this study
- Who is it for?
- Ages 14 to 65 years
- Conditions the study is for
- Donor Lymphocyte Infusion, Peripheral Blood Stem Cell Transplantation, Relapse
- What is being tested?
- Prophylactic DLI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- Jan 2019to Dec 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 14 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- disease in the non-remission (NR) state prior to transplantation, including primary induction failure, relapse untreated or refractory to reinduction chemotherapy.
- achieving CR1 with ≥3 cycles of induction of chemotherapy.
- carrying TP53, DNMT3a, TET2 or FLT3-ITD gene mutation.
Who cannot join
- early relapse, either molecular relapse or hematological relapse.
- primary or secondary graft failure.
- concomitant uncontrolled disease and/or organ dysfunction (infection, severe heart, renal, respiratory or hepatic failure…).
Trial locations and contacts
1 site in 1 country.
About this study
Unmanipulated allogenic peripheral blood stem cell transplantation (allo-PBSCT) has been an established treatment to cure high-risk leukemia/lymphoma. Relapse is the main cause of treatment failure for patients with relapsed/refractory disease or with very high-risk gene mutations such as TP53, TET2 and DNMT3a. Donor lymphocyte infusion (DLI) is an option to reduce relapse after allo-PBSCT for very high-risk disease without effective targeted therapy. In this study, the investigators aimed to compare the safety and efficacy of prophylactic DLI with G-CSF-primed peripheral blood progenitors for prevention of relapse after allo-PBSCT in patients with very high-risk leukemia/lymphoma.
Read the detailed description
Conventional DLI has invariably been associated with high rates of severe graft-versus-host disease (GVHD) and GVHD-related non-relapse mortality (NRM). Thus, in our previous studies, the DLI procedure has been modified to use G-CSF-mobilized peripheral blood stem cells (PBSCs) instead of steady-state lymphocytes. G-CSF mobilization results in the modulation of the polarization potential of T cells from Th1 to Th2. In addition, T-cell hyporesponsiveness is induced via the proliferation of dendritic cell 2 and monocytes and the down-regulation of CD28/B7. Furthermore, G-CSF augments NK-T-cell-dependent CD8+ cytotoxicity. These data constructed the rationale for the use of G-CSF-primed peripheral blood DLI to reduce DLI-associated GVHD and enhance the GVT effect of DLI. To date, there is no effective target therapy for acute leukemia with gene mutations such as DNMT3A, TET2 and TP53 and their response to chemotherapy and survival even after allogenic stem cell transplantation remains poor. Hypomethylating agents were reported to reverse the repression of HLA molecules and cancer testis antigens on leukemia cells, rendering them more sensitive to anti-leukemic activity mediated by DLI. The use of low-dose decitabine after allogenic stem cell transplantation was safe for early hematopoietic reconstitution. Therefore, decitabine was planned to be given prior to prophylactic DLI in the current study.
- Conditions
- Donor Lymphocyte Infusion, Peripheral Blood Stem Cell Transplantation, Relapse, Graft-versus-host Disease, Decitabine
- Being tested
- Prophylactic DLI
- Medical subject headings
- Recurrence, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prophylactic DLIBiological
Also called Decitabine (trade name Dacogen)
The G-CSF-mobilized PBSCs from cryopreserved cells of the graft were infused to the recipient at a dose of 2X10^7 CD3+ cells/kg recipient body weight. Decitabine (10 mg/m2, days 1 to 5) followed by prophylactic DLI would be given to those patients carrying TET2, DNMT3a or TP53 gene mutations.
| Study group | Role | What they receive |
|---|---|---|
| Prophylactic DLI | Experimental | The scheduled time of the first prophylactic DLI was +30 ~ +60 days after transplantation for HLA-matched sibling donors (MSD)-PBSCT recipients and +60 ~ +90 days after transplantation for HLA-haploidentical sibling donors (HID)-PBSCT recipients. Receives: Biological: Prophylactic DLI |
| No prophylactic DLI | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence of relapse at 1 year after randomization
Relapse was defined as hematologic recurrence of malignancies after transplantation. Cumulative incidence of relapse was analyzed in a competing risk framework using Gray's method.
Measured: 1 year
Cumulative incidence of non-relapse mortality (NRM) at 1 year after randomization
NRM was defined as death from any cause without relapse. Cumulative incidence of NRM was analyzed in a competing risk framework using Gray's method.
Measured: 1 year
Secondary outcomes (3)
Relapse-free survival (RFS) at 1 year after randomization
RFS will be evaluated in an intent-to-treat analysis by Kaplan Meier estimate and Log Rank test. Survival will be calculated from the date of randomization.
Measured: 1 year
Cumulative incidence of acute GVHD at 100 days after randomization
The cumulative incidence of acute GVHD was estimated considering the competing risks.
Measured: 100 days
Cumulative incidence of chronic GVHD at 1 year after randomization
The cumulative incidence of chronic GVHD was estimated considering the competing risks.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2018
- Study startJan 2019 (estimated)
- Primary completionDec 2020 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Donor Lymphocyte InfusionStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daihong Liu, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03771222
- Sponsor's protocol ID
- pDLI2018
- Status last verified
- Dec 2018
- First submitted
- 7 Dec 2018
- Last updated
- 13 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prophylactic Donor Lymphocyte Infusion After Allo-PBSCT for Patients With Very High-risk Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT03771222
- Acronym / sponsor ID
- pDLI2018
- Conditions
- Donor Lymphocyte Infusion, Peripheral Blood Stem Cell Transplantation, Relapse, Graft-versus-host Disease, Decitabine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- Jan 2019 (estimated)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 11 Dec 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.
Unmanipulated allogenic peripheral blood stem cell transplantation (allo-PBSCT) has been an established treatment to cure high-risk leukemia/lymphoma. Relapse is the main cause of treatment failure for patients with relapsed/refractory disease or with very high-risk gene mutations such as TP53, TET2 and DNMT3a. Donor lymphocyte infusion (DLI) is an option to reduce relapse after allo-PBSCT for very high-risk disease without effective targeted therapy. In this study, the investigators aimed to compare the safety and efficacy of prophylactic DLI with G-CSF-primed peripheral blood progenitors for prevention of relapse after allo-PBSCT in patients with very high-risk leukemia/lymphoma.
Detailed description
Conventional DLI has invariably been associated with high rates of severe graft-versus-host disease (GVHD) and GVHD-related non-relapse mortality (NRM). Thus, in our previous studies, the DLI procedure has been modified to use G-CSF-mobilized peripheral blood stem cells (PBSCs) instead of steady-state lymphocytes. G-CSF mobilization results in the modulation of the polarization potential of T cells from Th1 to Th2. In addition, T-cell hyporesponsiveness is induced via the proliferation of dendritic cell 2 and monocytes and the down-regulation of CD28/B7. Furthermore, G-CSF augments NK-T-cell-dependent CD8+ cytotoxicity. These data constructed the rationale for the use of G-CSF-primed peripheral blood DLI to reduce DLI-associated GVHD and enhance the GVT effect of DLI. To date, there is no effective target therapy for acute leukemia with gene mutations such as DNMT3A, TET2 and TP53 and their response to chemotherapy and survival even after allogenic stem cell transplantation remains poor. Hypomethylating agents were reported to reverse the repression of HLA molecules and cancer testis antigens on leukemia cells, rendering them more sensitive to anti-leukemic activity mediated by DLI. The use of low-dose decitabine after allogenic stem cell transplantation was safe for early hematopoietic reconstitution. Therefore, decitabine was planned to be given prior to prophylactic DLI in the current study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prophylactic DLI | Experimental | Biological: Prophylactic DLIThe scheduled time of the first prophylactic DLI was +30 ~ +60 days after transplantation for HLA-matched sibling donors (MSD)-PBSCT recipients and +60 ~ +90 days after transplantation for HLA-haploidentical sibling donors (HID)-PBSCT recipients. |
| No prophylactic DLI | No intervention | – |
Who may qualify
- Ages
- 14 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- disease in the non-remission (NR) state prior to transplantation, including primary induction failure, relapse untreated or refractory to reinduction chemotherapy.
- achieving CR1 with ≥3 cycles of induction of chemotherapy.
- carrying TP53, DNMT3a, TET2 or FLT3-ITD gene mutation.
Key exclusion criteria (3 listed)
- early relapse, either molecular relapse or hematological relapse.
- primary or secondary graft failure.
- concomitant uncontrolled disease and/or organ dysfunction (infection, severe heart, renal, respiratory or hepatic failure…).
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 |
|---|---|---|
| Prophylactic DLIAlso: Decitabine (trade name Dacogen)The G-CSF-mobilized PBSCs from cryopreserved cells of the graft were infused to the recipient at a dose of 2X10^7 CD3+ cells/kg recipient body weight. Decitabine (10 mg/m2, days 1 to 5) followed by prophylactic DLI would be given to those patients carrying TET2, DNMT3a or TP53 gene mutations. | Biological | Prophylactic DLI |
Primary outcome
Cumulative incidence of relapse at 1 year after randomization
Time frame: 1 year
Relapse was defined as hematologic recurrence of malignancies after transplantation. Cumulative incidence of relapse was analyzed in a competing risk framework using Gray's method.
Cumulative incidence of non-relapse mortality (NRM) at 1 year after randomization
Time frame: 1 year
NRM was defined as death from any cause without relapse. Cumulative incidence of NRM was analyzed in a competing risk framework using Gray's method.
3 secondary outcomes
Relapse-free survival (RFS) at 1 year after randomization
Time frame: 1 year
Cumulative incidence of acute GVHD at 100 days after randomization
Time frame: 100 days
Cumulative incidence of chronic GVHD at 1 year after randomization
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2018.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Prophylactic DLI in people with Donor Lymphocyte Infusion and Peripheral Blood Stem Cell Transplantation, run by Chinese PLA General Hospital at 1 site in China.
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 3 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 13 Dec 2018. 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 China. 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?
Results are not available in the source record.
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?
Cumulative incidence of relapse at 1 year after randomization (time frame: 1 year). The study lists 2 primary outcomes in all. 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 13 Dec 2018.