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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01807611
• Other study ID #: HAPNK1
• Secondary ID: NCI-2013-00609
• Status: Completed
• Phase: Phase 2
• Start date: May 16, 2013
• Est. completion date: September 27, 2021

Study information

• Verified date: August 2022
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: September 27, 2021
• Est. primary completion date: August 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Leukemia
• Lymphoma

Intervention

Radiation:
• Total Lymphoid Irradiation
Participants receive total lymphoid irradiation over four doses.

Drug:
• Fludarabine
Given IV.
• Cyclophosphamide
Given IV.
• Thiotepa
Given IV.
• Melphalan
Given IV.

Biological:
• HPC,A Infusion
Participants received infusions of HPC,A (CD34+ selected) and HPC,A (CD45RA depleted).
• TC-NK Infusion
Participants receive infusions of TC-NK.
• G-CSF
Participants receive G-CSF subcutaneously or intravenously. Donors receive G-CSF subcutaneously during cell mobilization.

Drug:
• 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.

Device:
• 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.

Drug:
• Mycophenolate mofetil
Given intravenously or orally.

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	Assisi Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	42 days post engraftment
Secondary	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.	One-year post-transplantation
Secondary	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.	One year post-transplantation
Secondary	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.	one year post-transplantation
Secondary	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.	100 days post-transplant for acute GVHD; one year post-transplant for chronic GVHD .
Secondary	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.	In the first 100 days after transplantation
Secondary	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.	100 days post-transplant for acute GVHD.
Secondary	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.	1 year post-transplant for chronic GVHD .

External Links

•   Clinical Trials Open at St. Jude
•   St. Jude Children's Research Hospital