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

NCT ID: NCT01807611

Last Updated: 2022-10-31

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

82 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-16

Study Completion Date

2021-09-27

Brief Summary

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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

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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.

Conditions

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Leukemia Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Transplant Recipients

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.

Group Type EXPERIMENTAL

Total Lymphoid Irradiation

Intervention Type RADIATION

Participants receive total lymphoid irradiation over four doses.

Fludarabine

Intervention Type DRUG

Given IV.

Cyclophosphamide

Intervention Type DRUG

Given IV.

Thiotepa

Intervention Type DRUG

Given IV.

Melphalan

Intervention Type DRUG

Given IV.

HPC,A Infusion

Intervention Type BIOLOGICAL

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

TC-NK Infusion

Intervention Type BIOLOGICAL

Participants receive infusions of TC-NK.

G-CSF

Intervention Type BIOLOGICAL

Participants receive G-CSF subcutaneously or intravenously.

Donors receive G-CSF subcutaneously during cell mobilization.

Mesna

Intervention Type 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.

CliniMACS

Intervention Type 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.

Mycophenolate mofetil

Intervention Type DRUG

Given intravenously or orally.

Interventions

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Total Lymphoid Irradiation

Participants receive total lymphoid irradiation over four doses.

Intervention Type RADIATION

Fludarabine

Given IV.

Intervention Type DRUG

Cyclophosphamide

Given IV.

Intervention Type DRUG

Thiotepa

Given IV.

Intervention Type DRUG

Melphalan

Given IV.

Intervention Type DRUG

HPC,A Infusion

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

Intervention Type BIOLOGICAL

TC-NK Infusion

Participants receive infusions of TC-NK.

Intervention Type BIOLOGICAL

G-CSF

Participants receive G-CSF subcutaneously or intravenously.

Donors receive G-CSF subcutaneously during cell mobilization.

Intervention Type BIOLOGICAL

Mesna

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 DRUG

CliniMACS

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 DEVICE

Mycophenolate mofetil

Given intravenously or orally.

Intervention Type DRUG

Other Intervention Names

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TLI Fludara Cytoxan Thioplex(R) by Immunex TESPA TSPA L-phenylalanine mustard Phenylalanine Mustard L-PAM L-sarcolysin Alkeran(R) Granulocyte Colony-Stimulating Factor Filgrastim Neupogen(R) Mesnex Cell Selection System MMF CellCept®

Eligibility Criteria

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Inclusion Criteria

* 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


* 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.
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assisi Foundation

OTHER

Sponsor Role collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Brandon M. Triplett, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

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St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Countries

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United States

References

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Naik S, Li Y, Talleur AC, Selukar S, Ashcraft E, Cheng C, Madden RM, Mamcarz E, Qudeimat A, Sharma A, Srinivasan A, Suliman AY, Epperly R, Obeng EA, Velasquez MP, Langfitt D, Schell S, Metais JY, Arnold PY, Hijano DR, Maron G, Merchant TE, Akel S, Leung W, Gottschalk S, Triplett BM. Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial. J Hematol Oncol. 2024 Jun 27;17(1):50. doi: 10.1186/s13045-024-01567-0.

Reference Type DERIVED
PMID: 38937803 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org

Clinical Trials Open at St. Jude

Other Identifiers

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NCI-2013-00609

Identifier Type: REGISTRY

Identifier Source: secondary_id

HAPNK1

Identifier Type: -

Identifier Source: org_study_id

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