Myelodysplastic Syndrome (MDS) Clinical Trial
Official title:
A Feasibility Trial of Post-Transplant Infusion of Allogeneic Regulatory T Cells and Allogeneic Conventional T Cells in Patients With Hematologic Malignancies Undergoing Allogeneic Myeloablative Hematopoietic Cell Transplantation From Haploidentical-Related Donors
Verified date | June 2018 |
Source | Stanford University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Patients with hematologic malignancies will receive myeloablative chemotherapy followed by stem cell rescue with bone marrow or hematopoietic peripheral blood stem cells collected by apheresis from a filgrastim- (G-CSF)-mobilized haploidentical related-donor, ie, hematopoietic peripheral blood stem cell transplant (HSCT).
Status | Terminated |
Enrollment | 10 |
Est. completion date | June 2014 |
Est. primary completion date | August 2012 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 60 Years |
Eligibility |
Inclusion Criteria RECIPIENT - Histopathologically-confirmed: - Acute leukemia (in first remission with poor risk factors and molecular prognosis) - Acute myelogenous leukemia (AML) with -5,-7, t (6;9), tri8, -11 - Acute lymphoblastic leukemia (ALL) with Ph+ t (9;22), t (4;22), (q34;q11) - Acute leukemia with refractory disease or > Complete Remission (CR) 1 - Chronic myelogenous leukemia (CML) (accelerated, blast or second chronic phase) - Myelodysplastic syndrome (in high and high intermediate risk categories) - Non-Hodgkin's lymphoma (NHL) with poor risk features and not suitable for autologous transplantation - Refractory Chronic lymphocytic leukemia (CLL) - At least 21 days from the end of most recent prior therapy to start of the transplant conditioning regimen - Must be < 60 years old at time of registration. - Karnofsky Performance Status (KPS) > 70% Must have related donor who is: - Genotypically human leukocyte antigen (HLA) -A, B,C and DR beta 1 (DRB1), DQ loci haploidentical to the recipient (but differing for 2 to 3 HLA alleles on the unshared haplotype in the graft-versus-host disease (GvHD) direction) - No HLA-matched sibling or matched-unrelated donor is identified. - Adequate cardiac and pulmonary function (left ventricular ejection fraction (LVEF) > 45%, diffusing capacity of the lungs for carbon monoxide (DLCO) >50% corrected for hemoglobin) - Serum creatinine < 1.5 mg/dL OR Creatinine clearance > 50 mL/min for those above serum creatinine at least 1.5 mg/dL - Serum bilirubin < 2.0 mg/dL - Alanine transaminase (ALT) < 2x upper normal limit (ULN) (unless secondary to disease) - No prior myeloablative therapy or hematopoietic cell transplantation DONOR: - Age = 70 years - Weight = 25 kg. - Medical history and physical examination confirm good health status as defined by institutional standards - Seronegative for HIV Ag within 30 days of apheresis collection for: - Hepatitis B surface antigen (sAg) or polymerase chain reaction (PCR) + - Hepatitis C ab or PCR+ - Genotypically haploidentical as determined by HLA typing - Female donors (child-bearing potential) must have a negative serum or urine beta-human chorionic gonadotropin (HCG) test within 3 weeks of mobilization - Capable of undergoing leukapheresis - Has adequate venous access - Willing to undergo insertion of a central catheter if leukapheresis via peripheral vein is inadequate - Capable of agreeing to second donation of peripheral blood progenitor cell (PBPC) (or a bone marrow harvest) should the patient fail to demonstrate sustained engraftment following the transplant - Institutional review board (IRB)-approved consent form signed by donor or legal guardian > 18 years of age Donor Selection in the priority order: - Recipient's biological mother preferred, if available - Other available haploidentical donors will be selected based upon the presence of natural killer (NK) alloreactivity between donor and recipient by high-resolution HLA typing of the C locus. An NK-alloreactive donor will be preferentially chosen. Recipients lacking a killer immunoglobulin-like receptor (KIR)-ligand present in the donor along with the corresponding KIR defines "NK alloreactivity". - If more than one NK-alloreactive donor is available, preference is to cytomegalovirus (CMV)-seronegative donor Exclusion Criteria RECIPIENT: - Suitable candidate for autologous transplantation or allogeneic transplantation with an available matched-related or matched-unrelated donor - Seropositive for: - HIV ab - Hepatitis B sAg or PCR+ - Hepatitis C ab or PCR+ - History of invasive Aspergillosis - Any active, uncontrolled bacterial, viral or fungal infection - Uncontrolled central nervous system (CNS) disease involvement - Lactating female DONOR: - Evidence of active infection or viral hepatitis - Factors of increased risk for complications from leukapheresis or granulocyte-colony stimulating factor (G-CSF) therapy - Lactating female - HIV-positive |
Country | Name | City | State |
---|---|---|---|
United States | Stanford University School of Medicine | Stanford | California |
Lead Sponsor | Collaborator |
---|---|
Everett Meyer | Doris Duke Charitable Foundation |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Maximum-tolerated Dose (MTD) of Regulatory and Conventional T-cells | The maximum-tolerated dose (MTD) was to be determined based on the safety and feasibility observed for a pre-determined set of cellular dose level combinations of regulatory T-cells (T-reg) and conventional T-cells (T-con). | 30 days after HSCT infusion | |
Secondary | Acute Graft-versus-Host-Disease (aGvHD) | The primary outcome was incidence of grade 3 or 4 acute graft-vs-host-disease (aGvHD), reported as the number of participants developing grade 3 or 4 aGvHD. | 1 year | |
Secondary | Overall Survival (OS), 1 Year | Assessed as subjects remaining alive 12 months after CD34+ cell infusion (ie, excludes death due to any cause) | 1 year | |
Secondary | Median Overall Survival (OS) | Reported as the median overall survival (OS) in months from infusion of the hematopoietic stem cells (HSCT) | 25 months | |
Secondary | To Measure the Incidence and Severity of Acute and Chronic GvHD | Population of participants that received HSCT and T-reg plus T-con, and developed actue, chronic, or any graft vs host disease (GvHD) | 1 year | |
Secondary | Serious Infections | Serious infections are reported as the number of participants experienced serious infections. | 1 year |
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