Targeting the IPA and Matching for the Non-Inherited Maternal Antigen for Haplo-Cord Transplantation

Summary

In this trial, we aim to improve the outcomes of haplo cord transplant. Haplo cord transplant is a novel and promising way to improve transplant outcomes. We hypothesize that identification of a graft that is at least 5/6 matched and inherited paternal antigen (IPA) targeted (i.e., cord blood grafts share one or more IPA antigens with the prospective recipient) is more important to the outcome of haplo cord transplant than the nucleated cell dose. The identification of such a graft for a large proportion of the subjects may necessitate accepting a lower umbilical cord graft dose.

In addition to a umbilical cord blood transplant, recipients will receive stem cells from a family member ( a haplo-identical donor) . After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device. The subject will undergo a chemotherapy conditioning regimen prior to transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past.

Conditions

• Hematologic Malignancies

Interventions

DEVICE

CliniMACS® CD34 Reagent System

The stem cells from the haplo-identical donor will be purified by a procedure called CD34 selection before they are given to the subject. A special device called the CliniMACS® CD34 Reagent System, which is not FDA approved, will be used for this purpose. The manufacturer of the device, Miltenyi Biotec, is providing the researchers access to the device for use in this research study. Because the stem cells from the haplo-identical donor are treated using the CliniMACS CD34 selection device, they cells are considered investigational.

DRUG

Fludarabine

Administer 30 mg/m2 /day intravenously x 5 days (Day -7 to Day -3) of a total dose of 150 mg/m2. Fludarabine will be dosed according to actual body weight.

DRUG

Melphalan

Administer 70mg/m2/day intravenously x 2 days. Melphalan will be dosed according to actual body weight. Cryotherapy with ice chips will be administered to prevent mucositis

DRUG

anti-thymocyte globulin (rabbit)

Administer 1.5 mg/kg/day intravenously x 3 days, total 4.5 mg/kg. ATG will be dosed according to actual body weight. The first dose will be infused over at least six hours, and subsequent doses over at least 4 hours. Pre-medications include acetaminophen 650 mg by mouth, diphenhydramine 25-50 mg by mouth or intravenously, and methylprednisolone 2 mg/kg (1 mg/ kg at the initiation and 1 mg/kg half-way through anti-thymocyte globulin administration).

DRUG

Rituximab

Administer one dose of 375 mg/m2 prior to or upon admission for all patients not previously exposed to rituximab or who have not received rituximab in the six months prior to transplant.

RADIATION

Total Body Irradiation

Patients at high risk of CNS relapse (e.g. ALL or Burkitt's lymphoma) or patients at high risk for graft rejection (i.e., donor-specific HLA antibodies, patients with severe aplastic anemia, or hemoglobinopathies) may receive 2 doses of TBI as part of the conditioning.

DRUG

Mycophenolate Mofetil

Will be started on Day -2 and given at a dose of 1000 mg every 8 hours until Day 28. Mycophenolae Mofetil can be given orally or intravenously. Infection, toxicity, very low patient weight (\<50 kilograms) may prompt earlier discontinuation or adjustment of doses.

DRUG

Tacrolimus

Administered 0.03/mg/kg/day intravenous continious infusion (CI) over 24 hours from 4pm Day -2 until engraftment or when subject is able to take orally, then tacrolimus approximately 0.09 mg/kg orally in 2 divided doses. Tacrolimus should be given at full dose to maintain levels of 5-15 ng/mL through Day 180, tapered by 20% every week thereafter. Infection, toxicity or other clinical circumstances may prompt earlier discontinuation or adjustment of doses. In the presence of Graft versus Host Disease, a clinical decision by the attending physician will determine if tacrolimus can be tapered or should be continued. Oral tacrolimus can be used when intravenous access for CI tacrolimus is unavailable.

Sponsors & Collaborators

• Weill Medical College of Cornell University

  lead OTHER

Principal Investigators

• Alexandra Gomez Arteaga, MD · Weill Medical College of Cornell University

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-10-16

Primary Completion

2023-08-09

Completion

2028-04-30

FDA Drug

Yes

Countries

• United States

Study Locations