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

Relapse Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03771222
• Other study ID #: pDLI2018
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 2019
• Est. completion date: December 2021

Study information

• Verified date: December 2018
• Source: Chinese PLA General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 65 Years

Eligibility

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…).

Related Conditions & MeSH terms

• Decitabine
• Donor Lymphocyte Infusion
• Graft vs Host Disease
• Graft-versus-host Disease
• Peripheral Blood Stem Cell Transplantation
• Relapse

Intervention

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.

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 year
Primary	Cumulative incidence of non-relapse mortality (NRM) at 1 year after randomization	NRM was de?ned 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	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.	1 year
Secondary	Cumulative incidence of acute GVHD at 100 days after randomization	The cumulative incidence of acute GVHD was estimated considering the competing risks.	100 days
Secondary	Cumulative incidence of chronic GVHD at 1 year after randomization	The cumulative incidence of chronic GVHD was estimated considering the competing risks.	1 year