NCT01621477

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

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

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 description

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 transplant related mortality and the rates of moderate and severe graft versus host disease at day 100. The investigators will also describe event-free, and disease-free survival at one year, as well as the rates of hematopoietic recovery and donor engraftment. Additionally, the investigators will study comprehensively immune reconstitution following T-cell replete haploidentical transplantation. PRIMARY OBJECTIVE: * Evaluate if the one-year survival is significantly improved in a group of children receiving a therapeutic regimen for high-risk hematologic malignancy that is relapsed or refractory despite previous allogeneic hematopoietic cell transplantation (HCT) using a novel reduced intensity conditioning and T-cell replete haploidentical donor hematopoietic stem cell plus NK cell transplantation. SECONDARY OBJECTIVES: * Estimate the incidence of malignant relapse, event-free survival, and disease free survival (DFS) at one-year post-transplantation. * Estimate incidence and severity of acute and chronic (GVHD). * Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.

Conditions

• Acute Lymphoblastic Leukemia
• Acute Myelocytic Leukemia
• Chronic Myelocytic Leukemia
• Juvenile Myelomonocytic Leukemia
• Myelodysplastic Syndrome
• Hodgkin or Non-Hodgkin Lymphoma
• Sarcoma, Myeloid

Interventions

Type	Name	Description
DRUG	clofarabine	Given on Day -9 and Day -8 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent
DRUG	cytarabine	Given on Day -9 and Day -8 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent
DRUG	busulfan	Given on Day -7 and Day -6 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent
DRUG	Plerixafor	Given on Day -7 and Day -6 (Day 0 is first stem cell infusion). Drug class: Hematopoietic Stem Cell Mobilizer
DRUG	cyclophosphamide	Given on Day -5 and Day +4 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent; immunosuppressive agent.
DRUG	antithymocyte globulin (rabbit)	Given on Day -4, Day -3, Day -2, and Day -1 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.
BIOLOGICAL	stem cells	Patients undergo T cell replete Hematopoietic stem cell infusion on Day 0 and Day +1. Patients undergo natural killer (NK) cell transplantation on day +6 (Day 0 is first stem cell infusion).
DRUG	Tacrolimus	Given on Day +11 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.
DRUG	mycophenolate mofetil	Given on Day +11 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.

Timeline

• Start date: 2012-08-01
• Primary completion: 2015-12-01
• Completion: 2015-12-01
• First posted: 2012-06-18
• Last updated: 2017-02-20
• Results posted: 2017-02-20

Locations

1 site across 1 country: United States