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

NCT01807611 | Completed Phase 2 Results FDA Drug FDA Device

• 2 other identifiers: HAPNK1NCI-2013-00609
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia; Lymphoma

Keywords

Haploidentical donor transplantation; NK cell

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Number of Transplant Recipients With Malignant Relapse

  One-year post-transplantation

• Event-free Survival

  One year post-transplantation

• Overall Survival

  one year post-transplantation

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

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

• Number of Transplant Recipients With Transplant-related Mortality (TRM)

  In the first 100 days after transplantation

Study Arms (1)

Transplant Recipients

EXPERIMENTAL

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.

Radiation: Total Lymphoid Irradiation; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Thiotepa; Drug: Melphalan; Biological: HPC,A Infusion; Biological: TC-NK Infusion; Biological: G-CSF; Drug: Mesna; Device: CliniMACS; Drug: Mycophenolate mofetil

Interventions

Total Lymphoid Irradiation RADIATION

Participants receive total lymphoid irradiation over four doses.

Also known as: TLI

Transplant Recipients

Fludarabine DRUG

Given IV.

Also known as: Fludara

Transplant Recipients

Cyclophosphamide DRUG

Given IV.

Also known as: Cytoxan

Transplant Recipients

Thiotepa DRUG

Given IV.

Also known as: Thioplex(R) by Immunex, TESPA, TSPA

Transplant Recipients

Melphalan DRUG

Given IV.

Also known as: L-phenylalanine mustard, Phenylalanine Mustard, L-PAM, L-sarcolysin, Alkeran(R)

Transplant Recipients

HPC,A Infusion BIOLOGICAL

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

Transplant Recipients

TC-NK Infusion BIOLOGICAL

Participants receive infusions of TC-NK.

Transplant Recipients

G-CSF BIOLOGICAL

Participants receive G-CSF subcutaneously or intravenously. Donors receive G-CSF subcutaneously during cell mobilization.

Also known as: Granulocyte Colony-Stimulating Factor, Filgrastim, Neupogen(R)

Transplant Recipients

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.

Also known as: Mesnex

Transplant Recipients

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.

Also known as: Cell Selection System

Transplant Recipients

Mycophenolate mofetil DRUG

Given intravenously or orally.

Also known as: MMF, CellCept®

Transplant Recipients

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Assisi Foundation: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Publications (1)

• 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.

  PMID: 38937803 DERIVED

Related Links

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

MeSH Terms

Conditions

Leukemia; Lymphoma

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Thiotepa; Melphalan; Granulocyte Colony-Stimulating Factor; Filgrastim; Mesna; Mycophenolic Acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Brandon M. Triplett, MD
• Organization: St. Jude Children's Research Hospital

referralinfo@stjude.org

866-278-5833

Study Officials

• Brandon M. Triplett, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2013
• First Posted: March 8, 2013
• Study Start: May 16, 2013
• Primary Completion: August 27, 2021
• Study Completion: September 27, 2021
• Last Updated: October 31, 2022
• Results First Posted: October 31, 2022

Record last verified: 2022-08

Locations

US (1)