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

St. Jude Children's Research Hospital

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Leukemia

Treatments

Drug: Thiotepa

Drug: Mycophenolate mofetil

Biological: HPC,A Infusion

Radiation: Total Lymphoid Irradiation

Device: CliniMACS

Drug: Cyclophosphamide

Drug: Fludarabine

Biological: TC-NK Infusion

Drug: Mesna

Drug: Melphalan

Biological: G-CSF

Study type

Interventional

Funder types

Other

Identifiers

NCT01807611

NCI-2013-00609 (Registry Identifier)

HAPNK1

Details and patient eligibility

About

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.

Full 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.

Enrollment

82 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

82 participants in 1 patient group

Transplant Recipients

Experimental group

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.

Treatment: