Clinical trial NCT01807611: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Keywords: Haploidentical donor transplantation
NK cell
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: Assisi Foundation
First posted: 2013-03-08
Enrollment: 82
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Transplant Recipients With Successful Engraftment
timeFrame: 42 days post engraftment
Secondary outcomes:
measure: Number of Transplant Recipients With Malignant Relapse
timeFrame: One-year post-transplantation
measure: Event-free Survival
timeFrame: One year post-transplantation
measure: Overall Survival
timeFrame: one year post-transplantation
measure: Number of Transplant Recipients With Acute and/or Chronic Graft Versus Host Disease (GVHD)
timeFrame: 100 days post-transplant for acute GVHD; one year post-transplant for chronic GVHD .
measure: Number of Transplant Recipients With Transplant-related Mortality (TRM)
timeFrame: In the first 100 days after transplantation
measure: Severity of Acute Graft Versus Host Disease (aGVHD)
timeFrame: 100 days post-transplant for acute GVHD.
measure: Severity of Chronic Graft Versus Host Disease (cGVHD)
timeFrame: 1 year post-transplant for chronic GVHD .
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Brandon M. Triplett, MD
role: PRINCIPAL_INVESTIGATOR
References: