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

St. Jude Children's Research Hospital

Status and phase

Terminated

Phase 2

Conditions

Hematological Malignancies

Treatments

Drug: Methylprednisolone

Radiation: Total lymphoid irradiation

Drug: Fludarabine

Drug: Thiotepa

Drug: Mesna

Drug: Mycophenolate mofetil

Drug: Cyclophosphamide

Drug: Tacrolimus

Drug: Melphalan

Biological: G-CSF

Biological: Lymphocyte infusions

Device: CliniMACS

Study type

Interventional

Funder types

Other

Identifiers

NCT02199041

NCI-2014-00526 (Registry Identifier)

HAPCORD

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), 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.

Full description

Prior to stem cell infusion, participants will receive a preparative regimen of total lymphoid irradiation (TLI), fludarabine, cyclophosphamide, melphalan, and thiotepa to prepare their bone marrow. Thereafter, they will receive a hematopoietic cell graft from a haploidentical donor and an unrelated umbilical cord blood donor. Post-transplantation immunosuppressive treatment will include tacrolimus and mycophenolate mofetil.

Enrollment

24 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria-Transplant Recipient:

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.
- Non-Hodgkin lymphoma in CR2 or subsequent.
- Juvenile myelomonocytic leukemia (JMML).
- Refractory hematologic malignancies [ALL, AML, chronic myeloid leukemia (CML) in blast crisis, Hodgkin or non-Hodgkin lymphoma] due to chemoresistant relapse or primary induction failure.
- All patients with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study.
Patient must fulfill pre-transplant evaluation:
- Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 40% or shortening fraction (SF) ≥ 25%.
- Creatinine clearance (CrCL) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2.
- Forced vital capacity (FVC) ≥ 50% of predicted value or pulse oximetry (Pox) ≥ 92% on room air.
- Karnofsky or Lansky performance score ≥ 50.
- Bilirubin ≤ 3 times the upper limit of normal for age.
- Alanine aminotransferase (ALT) ≤ 5x the upper limit of normal for age.
- Aspartate aminotransferase (AST) ≤ 5x the upper limit of normal for age.

Exclusion Criteria - Transplant Recipient:

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.

Inclusion criteria - haploidentical donor

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.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

24 participants in 1 patient group