Clinical trial NCT03771222: Prophylactic Donor Lymphocyte Infusion After Allo-PBSCT for Patients With Very High-risk Hematologic Malignancies
Official title: Prophylactic Donor Lymphocyte Infusion After Allo-PBSCT for Patients With Very High-risk Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Donor Lymphocyte Infusion
Peripheral Blood Stem Cell Transplantation
Relapse
Graft-versus-host Disease
Decitabine
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2018-12-11
Enrollment: 40
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: 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...).

Primary outcomes:
measure: Cumulative incidence of relapse at 1 year after randomization
timeFrame: 1 year
measure: Cumulative incidence of non-relapse mortality (NRM) at 1 year after randomization
timeFrame: 1 year
Secondary outcomes:
measure: Relapse-free survival (RFS) at 1 year after randomization
timeFrame: 1 year
measure: Cumulative incidence of acute GVHD at 100 days after randomization
timeFrame: 100 days
measure: Cumulative incidence of chronic GVHD at 1 year after randomization
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
References: