Clinical Trial: T-Cell Replete Haploidentical Donor Hematopoietic Stem Cell Plus Natural Killer (NK) Cell Transplantation in Patients With Hematologic Malignancies Relapsed or Refractory Despite Previous Allogeneic Transplant

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: T-Cell Replete Haploidentical Donor Hematopoietic Stem Cell Plus Natural Killer (NK) Cell Transplantation in Patients With Hematologic Malignancies Relapsed or Refractory Despite Previous Allogeneic T

Brief Summary: The primary aim of this protocol is to evaluate if the one-year survival is significantly improved in the group of patients who receive a T-cell replete haploidentical donor hematopoietic cell transplant (HCT) with a novel reduced intensity conditioning regimen. Study population will consist of patients (21 years or under) with hematologic malignancies that have relapsed or are refractory after prior allogeneic transplant. Toxicity will be evaluated by the rate of transplant related mortality and the rates of moderate and severe graft-versus-host disease (GvHD) at day 100. The investigators will describe event-free, and disease-free survival at one year, as well as the rates of hematopoietic recovery and donor engraftment and study comprehensively immune reconstitution following T-cell replete haploidentical transplantation.

Detailed Summary:

Patients with refractory hematologic malignancies, including those who develop recurrent disease after allogeneic hematopoietic cell transplantation, have a dismal prognosis. Historically, both regimen-related mortality and disease recurrence have been significant causes of treatment failure in this heavily pre-treated patient population. Our institution has utilized mismatched family member (haploidentical) donors for these patients for a number of years for the following reasons: (1) Only 30% of patients have matched related donors available; (2) transplantation can be performed more rapidly since the time to unrelated donor transplantation averages 3 to 4 months; (3) no other curative treatment options are available. These therapeutic interventions have been largely successful given the dismal prognosis in this patient group; however disease recurrence remains the most significant cause of treatment failure. To provide maximum benefit for this challenging population, the goals of a therapeutic transplant protocol should include: (1) a conditioning regimen that is well tolerated, even in a heavily pre-treated population; but it should also provide substantial antileukemia effects, and (2) should establish rapid immune recovery such that the patient may benefit from graft versus leukemia effect and early protection from life threatening infections while also limiting dangerous and counter-productive graft versus host disease.

The primary aim of this protocol will be to evaluate if the one-year survival is significantly improved in the group of patients receiving T-cell replete haploidentical donor HCT with a novel clofarabine, cytarabine, busulfan, plerixafor, cyclophosphamide, and ATG based reduced intensity conditioning regimen whose hematologic malignancy has relapsed or is refractory after prior allogeneic transplant. Toxicity will be evaluated by the rate of transpl
Sponsor: St. Jude Children's Research Hospital

Current Primary Outcome: One-year Survival (OS) [ Time Frame: One year post transplant ]

Original Primary Outcome: One-year survival [ Time Frame: One year post transplant ]

Current Secondary Outcome:

• Incidence of Malignant Relapse [ Time Frame: One year post transplantation. ]
  Estimate the incidence of malignant relapse at one year post-transplant. The number of participants with malignant relapse or progressive disease is given. Relapse was evaluated using standard WHO criteria for each disease.
• Event-Free Survival (EFS) [ Time Frame: one year post transplant ]
  Estimate the EFS at one-year post-transplantation. The event is defined as relapse or death due to any cause. The number of participants who were alive without relapse at one year post-transplant is reported.
• Disease-Free Survival (DFS) [ Time Frame: one year post transplant ]
  Estimate the DFS at one-year post-transplantation. The event is defined as relapse or death due to relapse. The number of participants who did not relapse up to one year post transplant is reported.
• Incidence and Severity of Acute Graft Versus Host Disease (GVHD) [ Time Frame: 100 days post transplant ]
  The number of participants with acute GVHD is given, organized by grade. Participants are graded on a scale from 1 to 4, with 1 being mild and 4 being severe.
• Incidence and Severity of Chronic Graft Versus Host Disease (GVHD) [ Time Frame: 100 days post transplant ]
  The severity of chronic GVHD will be described. Chronic GVHD was evaluated using NIH Consensus Global Severity Scoring. The number of participants with chronic GVHD is given, organized by severity.
• Number of Participants With Transplant Related Mortality (TRM) [ Time Frame: 100 days post transplant ]
  The number of participants who died due to TRM in the first 100 days post-transplant is given.

Original Secondary Outcome:

• Incidence of Malignant Relapse [ Time Frame: One year post transplantation. ]
  Estimate the incidence of malignant relapse at one-year post-transplantation.
• Event-Free Survival (EFS) [ Time Frame: one year post transplant ]
  Estimate the EFS at one-year post-transplantation. EFS is defined as the time from date of HCT to the minimum value of date of last follow-up, date of relapse, and date of death due to any cause. All participants surviving at the time of analysis will be censored.
• Disease-Free Survival (DFS) [ Time Frame: one year post transplant ]
  Estimate the DFS at one-year post-transplantation. DFS is defined as the time from date of HCT to the minimum value of date of last follow-up, date of relapse, and date of death due to relapse. All participants surviving at the time of analysis and those who die due to other causes will be censored at the time of their event.
• Incidence and severity of acute and chronic Graft Versus Host Disease (GVHD) [ Time Frame: 100 days post transplant ]
  Estimate incidence of acute and chronic GVHD and describe the severity of acute and chronic GVHD.
• Rate of transplant related mortality and transplant related morbidity [ Time Frame: 100 days post transplant ]
  Estimate the incidence of transplant related mortality and transplant related morbidity in the first 100 days after transplantation.

Information By: St. Jude Children's Research Hospital

Dates:
Date Received: June 8, 2012
Date Started: August 2012
Date Completion:
Last Updated: December 28, 2016
Last Verified: December 2016