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Completed

NCT Number: NCT01807611

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

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.

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Key information

Conditions

Leukemia Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

Up to 21 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Total lymphoid irradiation

Radiation

Participants receive total lymphoid irradiation over four doses.

Other names: TLI

Fludarabine

Drug

Given IV.

Other names: Fludara

Cyclophosphamide

Drug

Given IV.

Other names: Cytoxan

Thiotepa

Drug

Given IV.

Other names: Thioplex(R) by Immunex, TESPA, TSPA

melphalan

Drug

Given IV.

Other names: L-phenylalanine mustard, Phenylalanine Mustard, L-PAM, L-sarcolysin, Alkeran(R)

HPC,A Infusion

Biological

Participants received infusions of HPC,A (CD34+ selected) and HPC,A (CD45RA depleted).

TC-NK Infusion

Biological

Participants receive infusions of TC-NK.

G-CSF

Biological

Participants receive G-CSF subcutaneously or intravenously.

Donors receive G-CSF subcutaneously during cell mobilization.

Other names: Granulocyte Colony-Stimulating Factor, Filgrastim, Neupogen(R)

Mesna

Drug

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.

Other names: Mesnex

CliniMACS

Device

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.

Other names: Cell Selection System

Mycophenolate mofetil

Drug

Given intravenously or orally.

Other names: MMF, CellCept®

Primary outcomes

  1. Number of Transplant Recipients With Successful Engraftment

    Time frame: 42 days post 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 outcomes

  1. Number of Transplant Recipients With Malignant Relapse

    Time frame: One-year post-transplantation

    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.

  2. Event-free Survival

    Time frame: One year post-transplantation

    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.

  3. Overall Survival

    Time frame: one year post-transplantation

    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.

  4. Number of Transplant Recipients With Acute and/or Chronic Graft Versus Host Disease (GVHD)

    Time frame: 100 days post-transplant for acute GVHD; one year post-transplant for chronic 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.

  5. Number of Transplant Recipients With Transplant-related Mortality (TRM)

    Time frame: In the first 100 days after transplantation

    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.

  6. Severity of Acute Graft Versus Host Disease (aGVHD)

    Time frame: 100 days post-transplant for acute GVHD.

    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.

  7. Severity of Chronic Graft Versus Host Disease (cGVHD)

    Time frame: 1 year post-transplant for chronic GVHD .

    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.

Sponsors and collaborators

Lead sponsor

St. Jude Children's Research Hospital

Other

Collaborators

  • Assisi Foundation

Registry information

Official study title

Haploidentical Donor Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation With a TLI Based Conditioning Regimen in Patients With Hematologic Malignancies

Important dates

Study start
2013
Primary completion
2021
Study completion
2021
First posted
Mar 8, 2013
Registry last updated
Oct 31, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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