Combined T Cell Depleted Haploidentical Peripheral Blood Stem Cell and Unrelated Umbilical Cord Blood Transplantation in Patients With Hematologic Malignancies Using a Total Lymphoid Irradiation Based Preparative Regimen

NCT02199041 | Terminated Phase 2 Results DMC FDA Drug FDA Device

• 2 other identifiers: HAPCORDNCI-2014-00526
• Study Type: interventional
• Target: 24
• 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), matched unrelated donor (MURD) or killer-immunoglobulin receptors (KIR) ligand mismatched haploidentical donor identified, will receive a combined T cell depleted (TCD) haploidentical peripheral blood stem cell (PBSC) and unrelated umbilical cord blood transplantation (UCBT) using a total lymphoid irradiation (TLI) based preparative regimen. Primary objective:

• To estimate the incidence of donor derived neutrophil engraftment by day +42 post-transplant for participants with high-risk hematologic malignancies undergoing a total lymphoid irradiation (TLI)-based hematopoietic cell transplantation (HCT) using a T cell depleted (TCI) haploidentical donor peripheral blood stem cell (PBSC) donor combined with an unrelated umbilical cord blood (UCB) donor. Secondary objectives:
• Estimate the incidence of malignant relapse, event-free survival (EFS), and overall survival (OS) at one-year post-transplantation.
• Estimate the incidence and severity of acute and chronic graft versus host disease (GVHD) in the first 100 days after transplantation.
• Estimate the incidence of secondary graft failure transplant related mortality (TRM) and transplant related morbidity in the first 100 days after HCT.

Conditions

Hematological Malignancies

Keywords

Cord Blood; Haploidentical; Reduced Intensity Regimen

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Neutrophil Engraftment

  Neutrophil engraftment is defined as absolute neutrophil count (ANC) recovery of ≥ 0.5 x 10\^9/L (500/mm\^3) for three consecutive laboratory values obtained on different days (derived from either donor). Date of engraftment is the date of the first of the three consecutive laboratory values. The number of patients engrafted by day +42 post-transplant is provided.

  Until day 42 post-transplant

Secondary Outcomes (8)

• Number of Participants With Malignant Relapse

  One year after transplantation

• Number of Participants With Event-free Survival (EFS)

  One year after transplantation

• Number of Participants With Overall Survival (OS)

  One year after transplantation

• Number of Participants by Severity With Acute Graft Versus Host Disease (GVHD) in the First 100 Days After HCT

  100 days after transplantation

• Number of Participants by Severity With Chronic Graft Versus Host Disease (GVHD) in the First 100 Days After HCT

  100 days after transplantation

Study Arms (1)

Treatment

EXPERIMENTAL

Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion are prepared using the CliniMACS System.

Drug: Cyclophosphamide; Drug: Thiotepa; Drug: Fludarabine; Drug: Melphalan; Drug: Mesna; Biological: G-CSF; Drug: Mycophenolate mofetil; Drug: Tacrolimus; Drug: Methylprednisolone; Radiation: Total lymphoid irradiation; Biological: Lymphocyte infusions; Device: CliniMACS

Interventions

Cyclophosphamide DRUG

Given by intravenous infusion as part of the preparative regimen.

Also known as: Cytoxan

Treatment

Thiotepa DRUG

Given by intravenous infusion as part of the preparative regimen.

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

Treatment

Fludarabine DRUG

Given by intravenous infusion as part of the preparative regimen.

Also known as: Fludara

Treatment

Melphalan DRUG

Given by intravenous infusion as part of the preparative regimen.

Also known as: L-phenylalanine mustard, Phenylalanine mustard, L-PAM, L-sarcolysin, Alkeran

Treatment

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

Treatment

G-CSF BIOLOGICAL

Given either by intravenous infusion or subcutaneously daily until absolute neutrophil count (ANC) \>2000 for 3 consecutive days.

Also known as: Granulocyte colony-stimulating factor (C-CSF), Filgrastim, Neupogen(R)

Treatment

Mycophenolate mofetil DRUG

Given either orally or by intravenous infusion as part of the post-transplantation immunosuppression.

Also known as: MMF, CellCept(R)

Treatment

Tacrolimus DRUG

Given either orally or by intravenous infusion as part of the post-transplantation immunosuppression.

Also known as: FK506, Prograf(R), Protopic(R)

Treatment

Methylprednisolone DRUG

Given either intravenously or orally, if needed to treat graft-versus-host-disease (GVHD).

Also known as: Medrol(R), Solu-Medrol

Treatment

Total lymphoid irradiation RADIATION

TLI will be administered in divided fractions given at a minimum of 6 hours apart.

Also known as: TLI

Treatment

Lymphocyte infusions BIOLOGICAL

Donors will undergo haploidentical mobilization with G-CSF. Cells will be collected by leukapheresis over two days, then processed using the investigational CliniMACS device and CD34 Microbead reagent as directed by the manufacturer.

Also known as: Donor lymphocyte infusions, DLI

Treatment

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

Treatment

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 old.
• Does not have a suitable matched related/sibling donor (MSD) or volunteer matched unrelated donor (MUD) available in the necessary time for stem cell donation.
• Has a suitable partially human leukocyte antigen (HLA)-matched (≥ 3 of 6) family member donor.
• Has a partially HLA-matched single umbilical cord blood (UCB) unit (≥ 4 of 6) with adequate cell dose. UCB units must fulfill eligibility as outlined in 21 CFR 1271 and agency guidance.
• High-risk hematologic malignancy.
• High risk acute lymphocytic leukemia (ALL) in complete remission-1 (CR)1. \[Examples include, but not limited to t(9;22), hypodiploid,, M2 or greater marrow at the end of induction, infants with mixed lineage leukemia (MLL) fusion or t(4;11)\].
• ALL in High risk CR2. \[Examples include but not limited to t(9;22), bone marrow (BM) relapse \<36 mo CR1, T-ALL, very early (\< 6mo CR1) isolated central nervous system (CNS) relapse.\]
• ALL in CR3 or subsequent.
• Acute myeloid leukemia (AML) in high risk CR1. \[Examples include but not limited to preceding MDS, 5q-, -5, -7, FAB M6, FAB M7 not t(1;22), minimal residual disease (MRD) ≥ 5% on day 22 (AML08), M3 marrow after induction 1, M2 marrow after two cycles of induction, FLT3-ITD.\]
• AML in CR2 or subsequent.
• Therapy related AML, with prior malignancy in CR \> 12mo
• Myelodysplastic syndrome (MDS), primary or secondary
• Natural killer (NK) cell, biphenotypic, or undifferentiated leukemia in CR1 or subsequent.
• Chronic myeloid leukemia (CML) in accelerated phase, or in chronic phase with persistent molecular positivity or intolerance to tyrosine kinase inhibitor.
• Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous hematopoietic cell transplantation (HCT), or unable to mobilize stem cells for autologous HCT.

You may not qualify if:

• Patient has a suitable MSD, volunteer matched unrelated donor (MURD), or killer-immunoglobulin receptors (KIR) mismatched haploidentical donor available in the necessary time for stem cell donation.
• Patient has any other active malignancy other than the one for which HCT is indicated.
• Patient is pregnant as confirmed by positive serum or urine pregnancy test within 14 days prior to enrollment.
• Patient is breast feeding.
• Patient has Down Syndrome.
• Patient has a current uncontrolled bacterial, fungal, or viral infection per the judgment of the principal investigator.
• At least single haplotype matched (≥ 3 of 6) family member
• At least 18 years of age.
• Human immunodeficiency virus (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:
• Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR
• 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

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

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

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

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

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic 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; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

The study was halted early due to slow accrual.

Results Point of Contact

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

brandon.triplett@stjude.org

901-595-2766

Study Officials

• Brandon 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: July 9, 2014
• First Posted: July 24, 2014
• Study Start: July 11, 2014
• Primary Completion: May 23, 2017
• Study Completion: May 23, 2017
• Last Updated: February 7, 2018
• Results First Posted: February 7, 2018

Record last verified: 2017-08

Locations

US (1)