NCT01621477 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: TERMINATED
Registry last update: 2017-02-20

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

One-year Survival (OS)

→

outcome · POSTED

Incidence of Malignant Relapse

→

outcome · POSTED

Event-Free Survival (EFS)

→

outcome · POSTED

Disease-Free Survival (DFS)

→

outcome · POSTED

Incidence and Severity of Acute Graft Versus Host Disease (GVHD)

→

outcome · POSTED

Incidence and Severity of Chronic Graft Versus Host Disease (GVHD)

→

outcome · POSTED

Number of Participants With Transplant Related Mortality (TRM)

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion Criteria - for transplant recipient: * Age less than 21 years. * One of the following hematologic malignancies that has relapsed or remains refractory after prior allogeneic HCT: * Acute lymphoblastic leukemia (ALL) * Acute myeloid leukemia (AML) (including myeloid sarcoma) * Chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML), myelodysplastic syndrome (MDS), Hodgkin or non-Hodgkin lymphoma (NHL) * Has a suitable single haplotype matched (≥ 3 of 6) family member donor. * Does not have any other active malignancy other than the one for which this transplant is indicated. * If prior central nervous system (CNS) leukemia, it must be treated and have no evidence of CNS disease * Does not have current uncontrolled bacterial, fungal, or viral infection per the judgment of the principal investigator. * Patient must fulfill pre-transplant evaluation: * Left ventricular ejection fraction greater than 40%, or shortening fraction greater than or equal to 25%. * Creatinine clearance or Glomerular Filtration Rate of ≥70 ml/min/1.73m\^2. * Forced vital capacity (FVC) ≥ 40% of predicted value; or pulse oximetry ≥ 92% on room air if patient is unable to perform pulmonary function testing. * Karnofsky or Lansky (age-dependent) performance score ≥ 50. * Total bilirubin ≤ 1.5 times the upper limit of normal for age. * Alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal for age. * Not pregnant. If female with child bearing potential, must be confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment. * Not breast feeding. * Does not have active acute bronchiolitis obliterans or bronchiolitis obliterans organizing pneumonia. Inclusion Criteria - for donor: * At least single haplotype matched (≥ 3 of 6) family member, * At least 18 years of age. * Human immunodeficiency virus (HIV) negative. * Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female). * Not breast feeding. * A suitable donor is identified as either: * Has completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR * Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271. Exclusion Criteria: * Does not meet above inclusion criteria.
healthy Volunteers: false
maximum Age: 21 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

description
All study participants. Interventions: clofarabine, cytarabine, busulfan, plerixafor, cyclophosphamide, antithymocyte globulin (rabbit), stem cells, tacrolimus, mycophenolate mofetil
intervention Names
Drug: clofarabine
Drug: cytarabine
Drug: busulfan
Drug: Plerixafor
Drug: cyclophosphamide
Drug: antithymocyte globulin (rabbit)
Biological: stem cells
Drug: Tacrolimus
Drug: mycophenolate mofetil
label
Treatment
type
EXPERIMENTAL

interventions

arm Group Labels
Treatment
description
Given on Day -9 and Day -8 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent
name
clofarabine
other Names
Cl-F-Ara-A
CAFdA
Clofarex
Clolar(TM)
type
DRUG
arm Group Labels
Treatment
description
Given on Day -9 and Day -8 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent
name
cytarabine
other Names
Ara-C
type
DRUG
arm Group Labels
Treatment
description
Given on Day -7 and Day -6 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent
name
busulfan
other Names
Myleran(R)
Busulfex
type
DRUG
arm Group Labels
Treatment
description
Given on Day -7 and Day -6 (Day 0 is first stem cell infusion). Drug class: Hematopoietic Stem Cell Mobilizer
name
Plerixafor
other Names
AMD3100
Mozobil(R)
type
DRUG
arm Group Labels
Treatment
description
Given on Day -5 and Day +4 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent; immunosuppressive agent.
name
cyclophosphamide
other Names
Cytoxan
type
DRUG
arm Group Labels
Treatment
description
Given on Day -4, Day -3, Day -2, and Day -1 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.
name
antithymocyte globulin (rabbit)
other Names
Rabbit ATG
Rabbit Thymoglobulin(R)
type
DRUG
arm Group Labels
Treatment
description
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).
name
stem cells
other Names
HSC infusion
type
BIOLOGICAL
arm Group Labels
Treatment
description
Given on Day +11 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.
name
Tacrolimus
other Names
FK506
Prograf(R)
Protonic(R)
type
DRUG
arm Group Labels
Treatment
description
Given on Day +11 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.
name
mycophenolate mofetil
other Names
MMF
CellCept(R)
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 34
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Evaluate the number of participants alive at 1 year. The number of participants surviving to one-year post-transplantation is given.
measure
One-year Survival (OS)
time Frame
One year post transplant

secondary Outcomes

description
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.
measure
Incidence of Malignant Relapse
time Frame
One year post transplantation.
description
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.
measure
Event-Free Survival (EFS)
time Frame
one year post transplant
description
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.
measure
Disease-Free Survival (DFS)
time Frame
one year post transplant
description
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.
measure
Incidence and Severity of Acute Graft Versus Host Disease (GVHD)
time Frame
100 days post transplant
description
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.
measure
Incidence and Severity of Chronic Graft Versus Host Disease (GVHD)
time Frame
100 days post transplant
description
The number of participants who died due to TRM in the first 100 days post-transplant is given.
measure
Number of Participants With Transplant Related Mortality (TRM)
time Frame
100 days post transplant

Full study description

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 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.

Source references