Prophylactic Donor Lymphocyte Infusion After Allo-PBSCT for Patients With Very High-risk Hematologic Malignancies

December 11, 2018 updated by: Daihong Liu, Chinese PLA General Hospital
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100853
        • Chinese PLA General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

10 years to 61 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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…).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Prophylactic DLI
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.
Biological: Prophylactic DLI
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.
Other Names:
  • Decitabine (trade name Dacogen)
No Intervention: No prophylactic DLI

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
1 year
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.
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Relapse-free survival (RFS) at 1 year after randomization
Time Frame: 1 year
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.
1 year
Cumulative incidence of acute GVHD at 100 days after randomization
Time Frame: 100 days
The cumulative incidence of acute GVHD was estimated considering the competing risks.
100 days
Cumulative incidence of chronic GVHD at 1 year after randomization
Time Frame: 1 year
The cumulative incidence of chronic GVHD was estimated considering the competing risks.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Chinese PLA General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 7, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 7, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 11, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 13, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 11, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • pDLI2018

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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