Haploidentical Allogeneic Transplant With Post-transplant Infusion of Regulatory T-cells

• Status: Terminated
• Trial end date: 2014-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Everett Meyer; Ginna Laport
• Collaborator: Doris Duke Charitable Foundation
• Treatments: Antilymphocyte Serum; Fludarabine; Fludarabine phosphate; Melphalan; Thiotepa; Thymoglobulin; Vidarabine

Criteria

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