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Haploidentical Donor Hematopoietic Progenitor Cell and NK Cell Transplantation for Hematologic Malignancy

Primary Purpose

Leukemia, Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Total Lymphoid Irradiation
Fludarabine
Cyclophosphamide
Thiotepa
Melphalan
HPC,A Infusion
TC-NK Infusion
G-CSF
Mesna
CliniMACS
Mycophenolate mofetil
Sponsored by
St. Jude Children's Research Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring Haploidentical donor transplantation, NK cell

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria - Transplant Recipients:

  • Age less than or equal to 21 years.
  • Does not have a suitable MSD or volunteer MUD available in the necessary time for stem cell donation.
  • Has a suitable single haplotype matched (≥ 3 of 6) and family member donor.
  • High risk hematologic malignancy.
  • If prior CNS leukemia, it must be treated and in CNS CR
  • Does not have any other active malignancy other than the one for which this HCT is indicated.
  • No prior allogeneic HCT, and no autologous HCT within the previous 12 months.
  • Patient must fulfill pre-transplant evaluation

Inclusion Criteria - Haploidentical Donor:

  • At least single haplotype matched (≥ 3 of 6) family member
  • At least 18 years of age.
  • HIV negative.
  • Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female).
  • Not breast feeding.
  • Regarding eligibility, is identified as either: (1) Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR (2) 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.

Sites / Locations

  • St. Jude Children's Research Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Transplant Recipients

Arm Description

Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System.

Outcomes

Primary Outcome Measures

Number of Transplant Recipients With Successful Engraftment
Neutrophil engraftment will be determined using the parameters put forth by the Center for International Blood and Marrow Registry. Assessments will be made upon review of daily complete blood count and serial chimerism studies. Successful engraftment for the purposes of this objective will be patients who do not experience graft failure.

Secondary Outcome Measures

Number of Transplant Recipients With Malignant Relapse
Bone marrow studies for disease status evaluation will be performed at 1-year post-transplant. Testing will include a research evaluation for minimal residual disease.
Event-free Survival
The one-year event free survival is defined by the patient who has neither experienced relapse nor death within one year after post transplantation. And the rate is calculated by computing the ratio between total number of one year event free survival patients and the total number of patients.
Overall Survival
The one-year survival is defined by the patient who has not died within one year after post transplantation. And the rate is calculated by computing the ratio between total number of one year survival patients and the total number of patients.
Number of Transplant Recipients With Acute and/or Chronic Graft Versus Host Disease (GVHD)
Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The estimate will be the number of recipients who experienced GVHD divided by the total number of patients considered in this group.
Number of Transplant Recipients With Transplant-related Mortality (TRM)
Estimate the proportion of patients died within 100 days after the transplantation who has not experienced a relapse. The estimate will be the number of TRM divides the total number of patients considered in this group.
Severity of Acute Graft Versus Host Disease (aGVHD)
Ongoing assessment of toxicity will be done using the NCI CTCAE version 3.0. Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The severity of acute GvHD and chronic GvHD will be described. The analysis for this objective will be performed when the last evaluable participant has been followed for 100 days post transplant. Acute GvHD is graded from 1-4 with 4 being the worst outcome.
Severity of Chronic Graft Versus Host Disease (cGVHD)
Ongoing assessment of toxicity will be done using the NCI CTCAE version 3.0. Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The severity of acute GvHD and chronic GvHD will be described. The analysis for this objective will be performed when the last evaluable participant has been followed for 1 year post-transplant. Chronic GvHD is graded as "mild", "moderate" or "severe" with "severe" being the worst outcome.

Full Information

First Posted
March 5, 2013
Last Updated
October 28, 2022
Sponsor
St. Jude Children's Research Hospital
Collaborators
Assisi Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT01807611
Brief Title
Haploidentical Donor Hematopoietic Progenitor Cell and NK Cell Transplantation for Hematologic Malignancy
Official Title
Haploidentical Donor Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation With a TLI Based Conditioning Regimen in Patients With Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
May 16, 2013 (Actual)
Primary Completion Date
August 27, 2021 (Actual)
Study Completion Date
September 27, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Jude Children's Research Hospital
Collaborators
Assisi Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA) matched related/sibling donor (MSD) or matched unrelated donor (MUD) identified, will receive a haploidentical donor HCT with additional natural killer (NK) cells. The investigators anticipate enrollment of 75 donors and 75 recipients. PRIMARY OBJECTIVE: To estimate the rate of successful engraftment at day +42 post-transplant in patients who receive haploidentical donor stem cell plus NK cell transplantation with TLI based conditioning regimen for high risk hematologic malignancy. 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.
Detailed Description
Donors will undergo G-CSF mobilization of peripheral blood stem cells (PBSC) prior to undergoing two apheresis collections of hematopoietic progenitor cells (HPC,A) and one apheresis collection of therapeutic cell product of purified natural killer cells (TC-NK). The HPC products will be T-cell depleted (TCD) using the investigational CliniMACS device. CD34+ enrichment and CD45RA depletion will be utilized on sequential HPC grafts. Participants will undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, granulocyte colony stimulating factor (G-CSF), thiotepa, and melphalan. This is followed by infusions of donor cells that have been prepared using the CliniMACS system: HPC,A (CD34+ selected), HPC,A (CD45RA depleted), and TC-NK.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
Haploidentical donor transplantation, NK cell

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
82 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Transplant Recipients
Arm Type
Experimental
Arm Description
Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System.
Intervention Type
Radiation
Intervention Name(s)
Total Lymphoid Irradiation
Other Intervention Name(s)
TLI
Intervention Description
Participants receive total lymphoid irradiation over four doses.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Given IV.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
Given IV.
Intervention Type
Drug
Intervention Name(s)
Thiotepa
Other Intervention Name(s)
Thioplex(R) by Immunex, TESPA, TSPA
Intervention Description
Given IV.
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
L-phenylalanine mustard, Phenylalanine Mustard, L-PAM, L-sarcolysin, Alkeran(R)
Intervention Description
Given IV.
Intervention Type
Biological
Intervention Name(s)
HPC,A Infusion
Intervention Description
Participants received infusions of HPC,A (CD34+ selected) and HPC,A (CD45RA depleted).
Intervention Type
Biological
Intervention Name(s)
TC-NK Infusion
Intervention Description
Participants receive infusions of TC-NK.
Intervention Type
Biological
Intervention Name(s)
G-CSF
Other Intervention Name(s)
Granulocyte Colony-Stimulating Factor, Filgrastim, Neupogen(R)
Intervention Description
Participants receive G-CSF subcutaneously or intravenously. Donors receive G-CSF subcutaneously during cell mobilization.
Intervention Type
Drug
Intervention Name(s)
Mesna
Other Intervention Name(s)
Mesnex
Intervention Description
Mesna is generally dosed at approximately 25% of the cyclophosphamide dose. It is generally given intravenously prior to and again at 3, 6 and 9 hours following each dose of cyclophosphamide.
Intervention Type
Device
Intervention Name(s)
CliniMACS
Other Intervention Name(s)
Cell Selection System
Intervention Description
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Intervention Type
Drug
Intervention Name(s)
Mycophenolate mofetil
Other Intervention Name(s)
MMF, CellCept®
Intervention Description
Given intravenously or orally.
Primary Outcome Measure Information:
Title
Number of Transplant Recipients With Successful Engraftment
Description
Neutrophil engraftment will be determined using the parameters put forth by the Center for International Blood and Marrow Registry. Assessments will be made upon review of daily complete blood count and serial chimerism studies. Successful engraftment for the purposes of this objective will be patients who do not experience graft failure.
Time Frame
42 days post engraftment
Secondary Outcome Measure Information:
Title
Number of Transplant Recipients With Malignant Relapse
Description
Bone marrow studies for disease status evaluation will be performed at 1-year post-transplant. Testing will include a research evaluation for minimal residual disease.
Time Frame
One-year post-transplantation
Title
Event-free Survival
Description
The one-year event free survival is defined by the patient who has neither experienced relapse nor death within one year after post transplantation. And the rate is calculated by computing the ratio between total number of one year event free survival patients and the total number of patients.
Time Frame
One year post-transplantation
Title
Overall Survival
Description
The one-year survival is defined by the patient who has not died within one year after post transplantation. And the rate is calculated by computing the ratio between total number of one year survival patients and the total number of patients.
Time Frame
one year post-transplantation
Title
Number of Transplant Recipients With Acute and/or Chronic Graft Versus Host Disease (GVHD)
Description
Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The estimate will be the number of recipients who experienced GVHD divided by the total number of patients considered in this group.
Time Frame
100 days post-transplant for acute GVHD; one year post-transplant for chronic GVHD .
Title
Number of Transplant Recipients With Transplant-related Mortality (TRM)
Description
Estimate the proportion of patients died within 100 days after the transplantation who has not experienced a relapse. The estimate will be the number of TRM divides the total number of patients considered in this group.
Time Frame
In the first 100 days after transplantation
Title
Severity of Acute Graft Versus Host Disease (aGVHD)
Description
Ongoing assessment of toxicity will be done using the NCI CTCAE version 3.0. Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The severity of acute GvHD and chronic GvHD will be described. The analysis for this objective will be performed when the last evaluable participant has been followed for 100 days post transplant. Acute GvHD is graded from 1-4 with 4 being the worst outcome.
Time Frame
100 days post-transplant for acute GVHD.
Title
Severity of Chronic Graft Versus Host Disease (cGVHD)
Description
Ongoing assessment of toxicity will be done using the NCI CTCAE version 3.0. Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The severity of acute GvHD and chronic GvHD will be described. The analysis for this objective will be performed when the last evaluable participant has been followed for 1 year post-transplant. Chronic GvHD is graded as "mild", "moderate" or "severe" with "severe" being the worst outcome.
Time Frame
1 year post-transplant for chronic GVHD .

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria - Transplant Recipients: Age less than or equal to 21 years. Does not have a suitable MSD or volunteer MUD available in the necessary time for stem cell donation. Has a suitable single haplotype matched (≥ 3 of 6) and family member donor. High risk hematologic malignancy. If prior CNS leukemia, it must be treated and in CNS CR Does not have any other active malignancy other than the one for which this HCT is indicated. No prior allogeneic HCT, and no autologous HCT within the previous 12 months. Patient must fulfill pre-transplant evaluation Inclusion Criteria - Haploidentical Donor: At least single haplotype matched (≥ 3 of 6) family member At least 18 years of age. HIV negative. Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female). Not breast feeding. Regarding eligibility, is identified as either: (1) Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR (2) 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brandon M. Triplett, MD
Organizational Affiliation
St. Jude Children's Research Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.stjude.org
Description
St. Jude Children's Research Hospital
URL
http://www.stjude.org
Description
Clinical Trials Open at St. Jude

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Haploidentical Donor Hematopoietic Progenitor Cell and NK Cell Transplantation for Hematologic Malignancy

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