Ultra-Low Dose IL-2 Therapy as GVHD Prophylaxis in Haploidentical Allogeneic Stem Cell Transplantation

Summary

Background: \- Stem cell transplantation from a partially matched donor can lead to graft-versus-host disease (GVHD). Researchers want to learn how to improve these transplantations. Objective: \- To see if very low doses of Interleukin-2 after a partially matched transplantation prevent GVHD. Eligibility: * Recipients: age 18 65, with certain bone marrow or lymphatic system diseases and an available family member with partial tissue match. * Donors: age 18 80. Design: * Recipients will be screened with medical history, physical exam, and many tests including blood and tissue tying. * Donors will be screened with medical history, physical exam, blood tests and tissue typing. * Recipients will stay in the hospital 3 6 weeks. * All participants will have apheresis. Blood is drawn from one arm, run through a machine that collects white blood cells, then returned into the other arm. * Recipients will have: * Intravenous (IV) line placed under the skin and into a neck vein, to stay throughout transplant and recovery. They may also have a catheter inserted for collecting immune cells. * Bone marrow sample taken by needle. They will have 3 more after transplant. * Donors will have: * Filgrastim injected once daily for 5 6 days. * Stem and immune cells collected by another apheresis. * Recipients will get: * Eight 30-minute doses of radiation, sitting at a machine. * Donor immune cells by IV, 6 days before the transplant day. * Chemotherapy drugs by IV. \<TAB\>\<TAB\>- Donor stem cells by IV on transplant day. * After transplant, recipients will give self-injections of very low doses of Interleukin-2 once daily for about 12 weeks. * Before and after transplant, recipients will get medicine to suppress the immune system and antibiotics to prevent infections * Recipients must stay near NIH for 3 6 months after transplant. * All recipients and donors will have 3 years of follow-up.

Timeline

Start

2014-08-26

Primary completion

2018-05-23

Completion

2018-06-27

Publications

• Background Grosso D, Carabasi M, Filicko-O'Hara J, Kasner M, Wagner JL, Colombe B, Cornett Farley P, O'Hara W, Flomenberg P, Werner-Wasik M, Brunner J, Mookerjee B, Hyslop T, Weiss M, Flomenberg N. A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing. Blood. 2011 Oct 27;118(17):4732-9. doi: 10.1182/blood-2011-07-365338. Epub 2011 Aug 25.
• Background Barrett J, Gluckman E, Handgretinger R, Madrigal A. Point-counterpoint: haploidentical family donors versus cord blood transplantation. Biol Blood Marrow Transplant. 2011 Jan;17(1 Suppl):S89-93. doi: 10.1016/j.bbmt.2010.10.024. No abstract available.
• Background Fuchs EJ. Haploidentical transplantation for hematologic malignancies: where do we stand? Hematology Am Soc Hematol Educ Program. 2012;2012:230-6. doi: 10.1182/asheducation-2012.1.230.

Drugs

Indications