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
NCT ID: NCT02199041
Last Updated: 2018-02-07
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
24 participants
INTERVENTIONAL
2014-07-11
2017-05-23
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment
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.
Cyclophosphamide
Given by intravenous infusion as part of the preparative regimen.
Thiotepa
Given by intravenous infusion as part of the preparative regimen.
Fludarabine
Given by intravenous infusion as part of the preparative regimen.
Melphalan
Given by intravenous infusion as part of the preparative regimen.
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.
G-CSF
Given either by intravenous infusion or subcutaneously daily until absolute neutrophil count (ANC) \>2000 for 3 consecutive days.
Mycophenolate mofetil
Given either orally or by intravenous infusion as part of the post-transplantation immunosuppression.
Tacrolimus
Given either orally or by intravenous infusion as part of the post-transplantation immunosuppression.
Methylprednisolone
Given either intravenously or orally, if needed to treat graft-versus-host-disease (GVHD).
Total lymphoid irradiation
TLI will be administered in divided fractions given at a minimum of 6 hours apart.
Lymphocyte infusions
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.
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.
Interventions
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Cyclophosphamide
Given by intravenous infusion as part of the preparative regimen.
Thiotepa
Given by intravenous infusion as part of the preparative regimen.
Fludarabine
Given by intravenous infusion as part of the preparative regimen.
Melphalan
Given by intravenous infusion as part of the preparative regimen.
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.
G-CSF
Given either by intravenous infusion or subcutaneously daily until absolute neutrophil count (ANC) \>2000 for 3 consecutive days.
Mycophenolate mofetil
Given either orally or by intravenous infusion as part of the post-transplantation immunosuppression.
Tacrolimus
Given either orally or by intravenous infusion as part of the post-transplantation immunosuppression.
Methylprednisolone
Given either intravenously or orally, if needed to treat graft-versus-host-disease (GVHD).
Total lymphoid irradiation
TLI will be administered in divided fractions given at a minimum of 6 hours apart.
Lymphocyte infusions
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.
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
* 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.
Exclusion Criteria
* 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.
21 Years
ALL
No
Sponsors
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St. Jude Children's Research Hospital
OTHER
Responsible Party
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Principal Investigators
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Brandon Triplett, MD
Role: PRINCIPAL_INVESTIGATOR
St. Jude Children's Research Hospital
Locations
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St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Countries
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan: v. 0.0 - Initial
Document Type: Study Protocol and Statistical Analysis Plan: v. 0.1
Document Type: Study Protocol and Statistical Analysis Plan: v. 1.0
Document Type: Study Protocol and Statistical Analysis Plan: v. 2.0
Related Links
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St. Jude Children's Research Hospital
Clinical Trials Open at St. Jude
Other Identifiers
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NCI-2014-00526
Identifier Type: REGISTRY
Identifier Source: secondary_id
HAPCORD
Identifier Type: -
Identifier Source: org_study_id
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