NCT02259348 · REGISTRY CONDITION SEARCH

Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation

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: 2017-05-30

This pilot phase II trial studies how well a new reduced intensity conditioning regimen that includes haploidentical donor NK cells followed by the infusion of selectively T-cell depleted progenitor cell grafts work in treating younger patients with hematologic malignancies that have returned after or did not respond to treatment with a prior transplant. Giving chemotherapy and natural killer cells before a donor progenitor cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (progenitor cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's cells. When the healthy progenitor cells from a related donor are infused into the patient they make red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Removing specific T cells from the donor cells before the transplant may prevent this.

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

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baseline

Baseline characteristics

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outcome · POSTED

Percentage of Participants Engrafted by Day 42 Post-transplant

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outcome · POSTED

Incidence of Malignant Relapse

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outcome · POSTED

Event-free Survival (EFS)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Incidence and Severity of Acute GvHD

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outcome · POSTED

Incidence and Severity of Chronic GvHD

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outcome · POSTED

Rate of Transplant-related Mortality (TRM)

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outcome · POSTED

Mean of Days to Absolute Neutrophil Count (ANC) Engraftment

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outcome · POSTED

Median Days to Absolute Neutrophil Count (ANC) Engraftment

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Age less than or equal to 21 years. * One of the following hematologic malignancies that has relapsed or remains refractory after prior allogeneic hematopoietic cell transplant (HCT): * ALL, AML, Myeloid Sarcoma, CML, Juvenile myelomonocytic leukemia (JMML), myelodysplastic syndrome (MDS), 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 in CNS complete remission (CR) * Does not have current uncontrolled bacterial, fungal, or viral infection. * Patient must fulfill pre-transplant evaluation: * Left ventricular ejection fraction \> 40%, or shortening fraction ≥ 25%. * Creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2. * 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 (See Appendix A). * Bilirubin ≤ 3 times the upper limit of normal for age. * Alanine aminotransferase (ALT) ≤ 5 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 * DONOR: At least single haplotype matched (≥ 3 of 6) family member * DONOR: At least 18 years of age. * DONOR: HIV negative. * DONOR: Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female). * DONOR: Not breast feeding. * DONOR: Regarding donation eligibility, is identified as either: * 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.
healthy Volunteers: false
maximum Age: 21 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

description
Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
intervention Names
Drug: Cyclophosphamide
Drug: Fludarabine
Biological: G-CSF
Biological: Interleukin-2
Drug: Melphalan
Drug: Thiotepa
Drug: Rituximab
Biological: Natural killer cell therapy
Biological: T-cell depleted HPC transplant
Biological: CD45RA-depleted HPC transplant
label
Participants
type
EXPERIMENTAL

interventions

arm Group Labels
Participants
description
Given intravenously (IV)
name
Cyclophosphamide
other Names
Cytoxan
type
DRUG
arm Group Labels
Participants
description
Given IV
name
Fludarabine
other Names
Fludara
Fludarabine monophosphate
type
DRUG
arm Group Labels
Participants
description
Given IV or subcutaneously (SQ)
name
G-CSF
other Names
Filgrastim
Neupogen®
type
BIOLOGICAL
arm Group Labels
Participants
description
Given SQ
name
Interleukin-2
other Names
IL-2
Aldesleukin
type
BIOLOGICAL
arm Group Labels
Participants
description
Given IV
name
Melphalan
other Names
L-phenylalanine mustard
Phenylalanine mustard
L-PAM
L-sarcolysin
Alkeran®
type
DRUG
arm Group Labels
Participants
description
Given IV
name
Thiotepa
other Names
ThioplexV
TESPA
TSPA
type
DRUG
arm Group Labels
Participants
description
Given IV
name
Rituximab
other Names
Rituxan™
type
DRUG
arm Group Labels
Participants
description
Given IV
name
Natural killer cell therapy
other Names
NK cell therapy
type
BIOLOGICAL
arm Group Labels
Participants
description
T-cell depleted hematopoietic stem cells will be infused on day 0.
name
T-cell depleted HPC transplant
other Names
HPC,A Infusion(ɑ/β T cell depleted)
type
BIOLOGICAL
arm Group Labels
Participants
description
CD45RA depleted stem cells will be infused on day 1.
name
CD45RA-depleted HPC transplant
type
BIOLOGICAL

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 12
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
To estimate engraftment by day +42 post-transplant in patients who receive CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen that includes haploidentical NK cells. Engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm\^3 with evidence of donor cell engraftment.
measure
Percentage of Participants Engrafted by Day 42 Post-transplant
time Frame
Day 42 post transplantation

secondary Outcomes

description
The estimate of cumulative incidence of relapse will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The number of participants with incidence of malignant relapse is given. Relapse was evaluated using standard WHO criteria for each disease.
measure
Incidence of Malignant Relapse
time Frame
one year post transplantation
description
The Kaplan-Meier estimate of event-free survival (EFS) along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\\kme) available in the Department of Biostatistics at St. Jude, where EFS = min (date of last follow-up, date of relapse, date of graft failure, date of death due to any cause) - date of transplant, and all participants surviving at the time of analysis without events will be censored. The number of participants who did not experience any of these events through one year post-transplant is given.
measure
Event-free Survival (EFS)
time Frame
one year post transplantation
description
The Kaplan-Meier estimate of OS along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\\kme) available in the Department of Biostatistics at St. Jude, where OS = min (date of last follow-up, date of death) - date of transplant and all participants surviving at the time of analysis without events will be censored. The number of participants surviving to one-year post-transplantation is given.
measure
Overall Survival (OS)
time Frame
one year post transplantation
description
The cumulative incidence of acute GvHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The severity of acute GvHD. The number of participants with incidence by grade is given. Participants are graded on a scale from 1 to 4, with 1 being mild and 4 being severe.
measure
Incidence and Severity of Acute GvHD
time Frame
100 days post transplantation
description
The cumulative incidence of chronic GvHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The severity of chronic GvHD will be described. Chronic GvHD was evaluated using NIH Consensus Global Severity Scoring." The number of participants with incidence by severity is given.
measure
Incidence and Severity of Chronic GvHD
time Frame
one year post transplantation
description
The cumulative incidence of transplant related mortality will be estimated using Kalbfleisch-Prentice method. Deaths before day 100 because of other reasons are the competing risk events.
measure
Rate of Transplant-related Mortality (TRM)
time Frame
100 days post transplantation

Full study description

brief Summary: This pilot phase II trial studies how well a new reduced intensity conditioning regimen that includes haploidentical donor NK cells followed by the infusion of selectively T-cell depleted progenitor cell grafts work in treating younger patients with hematologic malignancies that have returned after or did not respond to treatment with a prior transplant. Giving chemotherapy and natural killer cells before a donor progenitor cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (progenitor cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's cells. When the healthy progenitor cells from a related donor are infused into the patient they make red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Removing specific T cells from the donor cells before the transplant may prevent this.
detailed Description: PRIMARY OBJECTIVE: * To estimate engraftment by day +42 post-transplant in patients who receive CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen that includes haploidentical natural killer (NK) cells. SECONDARY OBJECTIVES: * Estimate the incidence of malignant relapse, event-free survival, and overall survival 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. Blood progenitor cells will be collected from adult donors to be used for transplantation. Donor cells will be processed and filtered in a laboratory at St. Jude using a machine called the CliniMACS™ device, and later infused (transplanted) into the participant through his/her veins. Participants undergo a conditioning regimen beginning Day 21 prior to progenitor cell transplantation that includes chemotherapy medications and natural killer cells in preparation for transplantation. They will then receive T-cell depleted HPC transplant followed by CD45RA-depleted HPC transplant the following day.

Source references