Donor Stem Cell Transplant With No or Low-Intensity Chemotherapy Using Sirolimus and Treated Immune Cells to Treat Blood and Lymph Cancers

Summary

Background: Patients with cancers of the blood and immune system often benefit from transplants of stem cells from a genetically well-matched sibling. However, severe problems may follow these transplants because of the high-dose chemotherapy and radiation that accompany the procedure. Also, donated immune cells sometimes attack healthy tissues in a reaction called graft-versus-host disease (GVHD), damaging organs such as the liver, intestines and skin. To reduce toxicity of high-dose preparative chemotherapy, this study performs allogeneic transplant after low doses of chemotherapy. In an attempt to improve anti-tumor effects without increasing GVHD, this study uses donor immune cells (T helper 2 (Th2) cells) grown in the laboratory; some patients will receive standard donor immune cells (not grown in laboratory). All patients will receive immune modulating drugs sirolimus and cyclosporine to prevent GVHD. Objective: To determine the safety, treatment effects and rate of GVHD in patients receiving transplants that use low-intensity chemotherapy, sirolimus plus cyclosporine, and transplant booster with either Th2 cells or standard immune cells. Eligibility: Patients 16 to 75 years of age with acute or chronic leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, or myelodysplastic syndrome. Patients must have a suitable genetically matched sibling donor and adequate kidney, heart and lung function. Design: The protocol has three treatment groups: cohort 1, Th2 booster at two weeks post-transplant; cohort 2, standard T cell booster at two weeks post-transplant; cohort 3, multiple infusion of Th2 cells. Condition: Hematologic Neoplasms, Myeloproliferative Disorders Intervention: Biological; therapeutic allogeneic lymphocytes Drug: Sirolimus Study Type: Interventional Study Design: Primary Purpose: Treatment Phase: Phase II

Timeline

Start

2004-01-01

Primary completion

2017-07-20

Completion

2017-08-16

Outcome

Outcome not reported

Stopped (Enrollment): “Premature closure due to inability to accrue to ARM IVD, cohorts 1 and 2”

Publications

• Background Armitage JO. Bone marrow transplantation. N Engl J Med. 1994 Mar 24;330(12):827-38. doi: 10.1056/NEJM199403243301206. No abstract available.
• Background Jamshed S, Fowler DH, Neelapu SS, Dean RM, Steinberg SM, Odom J, Bryant K, Hakim F, Bishop MR. EPOCH-F: a novel salvage regimen for multiple myeloma before reduced-intensity allogeneic hematopoietic SCT. Bone Marrow Transplant. 2011 May;46(5):676-81. doi: 10.1038/bmt.2010.173. Epub 2010 Jul 26.
• Results Fowler DH, Mossoba ME, Steinberg SM, Halverson DC, Stroncek D, Khuu HM, Hakim FT, Castiello L, Sabatino M, Leitman SF, Mariotti J, Gea-Banacloche JC, Sportes C, Hardy NM, Hickstein DD, Pavletic SZ, Rowley S, Goy A, Donato M, Korngold R, Pecora A, Levine BL, June CH, Gress RE, Bishop MR. Phase 2 clinical trial of rapamycin-resistant donor CD4+ Th2/Th1 (T-Rapa) cells after low-intensity allogeneic hematopoietic cell transplantation. Blood. 2013 Apr 11;121(15):2864-74. doi: 10.1182/blood-2012-08-446872. Epub 2013 Feb 20.

Drugs

Indications