Minimal Residual Disease,Acute Leukemia, Hypomethylating Agents, Donor Lymphocyte Infusion, Allogeneic Hematopoietic Cell TransplantationPhase 2/3NCT03662087
HMA+DLI vs DLI Preemptive Therapy Based on MRD for AL Undergoing Allo-HSCT
A Phase 2/3 study testing HMA+DLI and DLI in people with Minimal Residual Disease,Acute Leukemia, Hypomethylating Agents, Donor Lymphocyte Infusion, Allogeneic Hematopoietic Cell Transplantation, run by Nanfang Hospital, Southern Medical University at 1 site in China.
Trial summary
Allogeneic hematopoietic cell transplantation (Allo-HSCT) is an effective therapy for acute leukemia, but relapse is the most common problem affecting long-term survivors of allo-HSCT. Read more about this study
- Who is it for?
- Ages 14 to 65 years
- Conditions the study is for
- Minimal Residual Disease,Acute Leukemia, Hypomethylating Agents, Donor Lymphocyte Infusion, Allogeneic Hematopoietic Cell Transplantation
- What is being tested?
- HMA+DLI and DLI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- Oct 2018to Oct 2022
- Phase
- Phase 2/3
- 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
- A patient age of 14-65 years. AL patients who achieved CR at pre-transplantation undergoing allo-HSCT. Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
Who cannot join
- AL patients who were in NR at pre-transplantation undergoing allo-HSCT. Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure). Patients with any conditions not suitable for the trial (investigators' decision).
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Hematology,Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, 510515
Hua Jin, +86-020-61641613, 499509173@qq.com
About this study
Official title: Hypomethylating Agents + Donor Lymphocyte Infusion vs Donor Lymphocyte Infusion Preemptive Therapy Based on Minimal Residual Disease for Acute Leukemia Undergoing Allogenetic Hematopoietic Stem Cell Transplantation
Allogeneic hematopoietic cell transplantation (Allo-HSCT) is an effective therapy for acute leukemia, but relapse is the most common problem affecting long-term survivors of allo-HSCT. Therapy options for relapse include stopping immune suppression, re-induction of chemotherapy, donor lymphocyte infusion (DLI) or combination therapy. In this prospective randomized controlled study, the safety and efficacy of hypomethylating agents (HMA) + DLI and DLI preemptive therapy based on minimal residual disease in acute leukemia undergoing allo-HSCT are evaluated.
Read the detailed description
Allogeneic hematopoietic cell transplantation (Allo-HSCT) is an effective therapy for acute leukemia, but relapse is the most common problem affecting long-term survivors of allo-HSCT. Therapy options for relapse include stopping immune suppression, re-induction of chemotherapy, donor lymphocyte infusion (DLI) or combination therapy. One method of solving relapse is to intervene before hematologic or pathologic relapse occurs based on minimal residual disease (MRD) . DLI is an effective post-transplantation therapy based on MRD for relapse. Whether combination of hypomethylating agents (HMA) and DLI could improve outcomes remains unclear. In this prospective randomized controlled study, the safety and efficacy of HMA+DLI and DLI preemptive therapy based on minimal residual disease in acute leukemia undergoing allo-HSCT are evaluated.
- Being tested
- HMA+DLI, DLI
- Medical subject headings
- Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HMA+DLICombination product
HMA: Decitabine was administered at 20mg/m2/day for five consecutive days or Ara-C was administered at 75mg/m2/day for seven consecutive days. DLI was administered at a median dose of 1.0 (range 0.7-1.4) ×10*8 mononuclear cells/kg.
DLIBiological
DLI was administered at a median dose of 1.0 (range 0.7-1.4) ×10*8 mononuclear cells/kg.
| Study group | Role | What they receive |
|---|---|---|
| HMA+DLI | Experimental | For AL patients who achieved CR at pre-transplantation undergoing allo-HSCT, DLI was not given and immunosuppressant were withdrawn if patients were MRD persistently negative. MRD status were monitored every 30 days. If patients were MRD negative by Day+30 post-transplantation, MRD status would be continued to be monitored by Day+60. If patients were MRD positive by Day+30 post-transplantation, immunosuppressant were withdrawn. If MRD were persistently positive until Day+60 or MRD changed from negative by Day+30 to positive by Day +60 post-transplantation, HMA and DLI were given. DLI was given 48 hours after administration of HMA. DLI was given monthly until GVHD occurred or MRD became negative or a total of four times. If MRD changed from positive by Day+30 to negative by Day+60 post-transplantation, MRD status would be continued to be monitored by Day+90 post-transplantation. If patients were MRD positive by Day+90 post-transplantation, HMA and DLI were given as shown above. Receives: Combination Product: HMA+DLI |
| DLI | Experimental | For AL patients who achieved CR at pre-transplantation undergoing allo-HSCT, DLI was not given and immunosuppressant were withdrawn if patients were MRD persistently negative. MRD status were monitored every 30 days. If patients were MRD negative by Day+30 post-transplantation, MRD status would be continued to be monitored by Day+60 post-transplantation. If patients were MRD positive by Day+30 post-transplantation, immunosuppressant were withdrawn. If MRD were persistently positive until Day+60 or MRD changed from negative by Day+30 to positive by Day+60 post-transplantation, DLI was given. DLI was given monthly until GVHD occurred or MRD became negative or a total of four times. If MRD changed from positive by Day+30 to negative by Day+60 post-transplantation, MRD status would be continued to be monitored by Day+90 post-transplantation. If patients were MRD positive by Day+90 post-transplantation, DLI was given as shown above. Receives: Biological: DLI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relapse
Relapse was defined by reappearance of blasts in the peripheral blood, recurrence of BM blasts >5%, or development of extramedullary disease infiltrates at any site
Measured: 2 years
Secondary outcomes (5)
Disease-free survival (DFS)
DFS was defined as the time from transplantation to relapse or death in remission
Measured: 2 years
Overall survival (OS)
OS was defined as the time from transplantation to death from all causes
Measured: 2 years
Transplant-related mortality (TRM)
TRM was defined as death from any cause except relapse
Measured: 2 years
Incidence of acute GVHD
Acute GVHD was graded according to standard criteria
Measured: 100 days
Incidence of chronic GVHD
Chronic GVHD was assessed in patients alive after day 100
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2018
- Study startOct 2018 (estimated)
- Primary completionOct 2021 (estimated)
- Study completionOct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Minimal Residual Disease,Acute Leukemia, Hypomethylating Agents, Donor Lymphocyte Infusion, Allogeneic Hematopoietic 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanfang Hospital, Southern Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Qifa Liu, Nanfang Hospital, Southern Medical University
- Investigators
- Qifa Liu, Principal investigator, Nanfang Hospital, Southern Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03662087
- Sponsor's protocol ID
- HMA+DLI vs DLI-MRD-AL-2018
- Status last verified
- Jul 2018
- First submitted
- 5 Sep 2018
- Last updated
- 7 Sep 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Yan CH, Liu DH, Liu KY, Xu LP, Liu YR, Chen H, Han W, Wang Y, Qin YZ, Huang XJ. Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood. 2012 Apr 5;119(14):3256-62. doi: 10.1182/blood-2011-09-380386. Epub 2012 Feb 14.
PubMed 22337715
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypomethylating Agents + Donor Lymphocyte Infusion vs Donor Lymphocyte Infusion Preemptive Therapy Based on Minimal Residual Disease for Acute Leukemia Undergoing Allogenetic Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT03662087
- Acronym / sponsor ID
- HMA+DLI vs DLI-MRD-AL-2018
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Nanfang Hospital, Southern Medical UniversityUniversity, hospital or other
- Study start
- Oct 2018 (estimated)
- Primary completion
- Oct 2021 (estimated)
- Study completion
- Oct 2022 (estimated)
- First posted
- 7 Sep 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.
Allogeneic hematopoietic cell transplantation (Allo-HSCT) is an effective therapy for acute leukemia, but relapse is the most common problem affecting long-term survivors of allo-HSCT. Therapy options for relapse include stopping immune suppression, re-induction of chemotherapy, donor lymphocyte infusion (DLI) or combination therapy. In this prospective randomized controlled study, the safety and efficacy of hypomethylating agents (HMA) + DLI and DLI preemptive therapy based on minimal residual disease in acute leukemia undergoing allo-HSCT are evaluated.
Detailed description
Allogeneic hematopoietic cell transplantation (Allo-HSCT) is an effective therapy for acute leukemia, but relapse is the most common problem affecting long-term survivors of allo-HSCT. Therapy options for relapse include stopping immune suppression, re-induction of chemotherapy, donor lymphocyte infusion (DLI) or combination therapy. One method of solving relapse is to intervene before hematologic or pathologic relapse occurs based on minimal residual disease (MRD) . DLI is an effective post-transplantation therapy based on MRD for relapse. Whether combination of hypomethylating agents (HMA) and DLI could improve outcomes remains unclear. In this prospective randomized controlled study, the safety and efficacy of HMA+DLI and DLI preemptive therapy based on minimal residual disease in acute leukemia undergoing allo-HSCT are evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HMA+DLI | Experimental | Combination Product: HMA+DLIFor AL patients who achieved CR at pre-transplantation undergoing allo-HSCT, DLI was not given and immunosuppressant were withdrawn if patients were MRD persistently negative. MRD status were monitored every 30 days. If patients were MRD negative by Day+30 post-transplantation, MRD status would be continued to be monitored by Day+60. If patients were MRD positive by Day+30 post-transplantation, immunosuppressant were withdrawn. If MRD were persistently positive until Day+60 or MRD changed from negative by Day+30 to positive by Day +60 post-transplantation, HMA and DLI were given. DLI was given 48 hours after administration of HMA. DLI was given monthly until GVHD occurred or MRD became negative or a total of four times. If MRD changed from positive by Day+30 to negative by Day+60 post-transplantation, MRD status would be continued to be monitored by Day+90 post-transplantation. If patients were MRD positive by Day+90 post-transplantation, HMA and DLI were given as shown above. |
| DLI | Experimental | Biological: DLIFor AL patients who achieved CR at pre-transplantation undergoing allo-HSCT, DLI was not given and immunosuppressant were withdrawn if patients were MRD persistently negative. MRD status were monitored every 30 days. If patients were MRD negative by Day+30 post-transplantation, MRD status would be continued to be monitored by Day+60 post-transplantation. If patients were MRD positive by Day+30 post-transplantation, immunosuppressant were withdrawn. If MRD were persistently positive until Day+60 or MRD changed from negative by Day+30 to positive by Day+60 post-transplantation, DLI was given. DLI was given monthly until GVHD occurred or MRD became negative or a total of four times. If MRD changed from positive by Day+30 to negative by Day+60 post-transplantation, MRD status would be continued to be monitored by Day+90 post-transplantation. If patients were MRD positive by Day+90 post-transplantation, DLI was given as shown above. |
Who may qualify
- Ages
- 14 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- A patient age of 14-65 years. AL patients who achieved CR at pre-transplantation undergoing allo-HSCT. Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
Key exclusion criteria (1 listed)
- AL patients who were in NR at pre-transplantation undergoing allo-HSCT. Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure). Patients with any conditions not suitable for the trial (investigators' decision).
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 |
|---|---|---|
| HMA+DLIHMA: Decitabine was administered at 20mg/m2/day for five consecutive days or Ara-C was administered at 75mg/m2/day for seven consecutive days. DLI was administered at a median dose of 1.0 (range 0.7-1.4) ×10*8 mononuclear cells/kg. | Combination product | HMA+DLI |
| DLIDLI was administered at a median dose of 1.0 (range 0.7-1.4) ×10*8 mononuclear cells/kg. | Biological | DLI |
Primary outcome
Relapse
Time frame: 2 years
Relapse was defined by reappearance of blasts in the peripheral blood, recurrence of BM blasts >5%, or development of extramedullary disease infiltrates at any site
5 secondary outcomes
Disease-free survival (DFS)
Time frame: 2 years
Overall survival (OS)
Time frame: 2 years
Transplant-related mortality (TRM)
Time frame: 2 years
Incidence of acute GVHD
Time frame: 100 days
Incidence of chronic GVHD
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2018.
- Background: PubMed 22337715Yan CH, Liu DH, Liu KY, Xu LP, Liu YR, Chen H, Han W, Wang Y, Qin YZ, Huang XJ. Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood. 2012 Apr 5;119(14):3256-62. doi: 10.1182/blood-2011-09-380386. Epub 2012 Feb 14.
- 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.
Qifa Liu principal investigator
Nanfang Hospital, Southern Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing HMA+DLI and DLI in people with Minimal Residual Disease,Acute Leukemia, Hypomethylating Agents, Donor Lymphocyte Infusion, Allogeneic Hematopoietic Cell Transplantation, run by Nanfang Hospital, Southern Medical University 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 1 inclusion and 1 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 7 Sep 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Contact Hua Jin (+86-020-61641613, 499509173@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relapse (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03662087, which also lists 1 linked publication.
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 7 Sep 2018.