Clinical Trial: Stem Cell Transplant Therapy With Campath-1H for Treating Advanced Mycosis Fungoides and Sezary Syndrome

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase I/II Study of HLA-matched Mobilized Peripheral Blood Hematopoietic Stem Cell Transplantation for Advanced Mycosis Fungoides/Sezary Syndrome Using Nonmyeloablative

Brief Summary:

This study will investigate the safety and effectiveness of a modified donor stem cell transplantation procedure for treating advanced mycosis fungoides (MF), a lymphoma primarily affecting the skin, and Sezary syndrome (SS), a leukemic form of the disease. Donated stem cells (cells produced by the bone marrow that mature into the different blood components white cells, red cells and platelets) can cure patients with certain leukemias and lymphomas and multiple myeloma. These cells generate a completely new, functioning bone marrow. In addition, immune cells from the donor grow and generate a new immune system to help fight infections. The new immune cells also attack any residual tumor cells left in the body after intensive chemotherapy. However, stem cell transplantation carries a significant risk of death, because it requires completely suppressing the immune system with high-dose chemotherapy and radiation. In addition, lymphocytes from the donor may cause what is called graft vs. host disease (GvHD), in which these cells see the patient s cells as foreign and mount an immune response to destroy them. To try to reduce these risks, patients in this study will be given low-dose chemotherapy and no radiation, a regimen that is easier for the body to tolerate and involves a shorter period of complete immune suppression. In addition, a monoclonal antibody called Campath-1H will be given to target lymphocytes, including those that have become cancerous.

Patients with advanced MF or SS who are between 18 and 70 years of age and have a matched family donor 18 years of age or older may be eligible for this study. Candidates will have a medical history, physical examination and blood tests, lung and heart function tests, X-rays of the chest, eye examination, and bone marrow sampling (withdrawal through a needle of about a tablespoon of marrow from the hip bone), and small skin

Detailed Summary:

Primary cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders characterized by localization of neoplastic T cells to the skin at presentation. Mycosis fungoides (MF) and its leukemic variant Sezary syndrome (SS) are the most prevalent forms of CTCL. While early stage MF is restricted to patches and plaques involving the skin, most patients eventually develop cutaneous tumors, generalized erythroderma, or dissemination to peripheral blood, lymph nodes or visceral organs. Currently existing therapy of tumor-stage and disseminated CTCL is palliative, with most patients dying within 1-5 years. The presence of CD8+ cells in close proximity to dermal neoplastic infiltrates in early stages of the disease, and the clinical response seen with some immunomodulatory agents suggests that CTCL may be potential targets for immunotherapy-based interventions.

Allogeneic stem cell transplantation is a curative treatment modality successfully employed in a number of hematologic malignancies. The curative effect of this approach is in part mediated by donor-derived T lymphocytes with reactivity for patient leukemic cells. The power of this graft versus leukemia effect (GVL) is best illustrated in patients with relapsed Chronic Myeloid Luekema (CML) after an allogeneic bone marrow transplant, in whom a single donor lymphocyte infusion (DLI) can induce remission. We hypothesize that neoplastic T cells in MF/SS may similarly be susceptible to a graft vs. tumor (GVT) effect. Unfortunately, advanced patient age and a 25% to 35% risk of transplant related mortality (TRM) preclude the use of conventional 'dose- intensive' allogeneic peripheral blood stem cell transplantation (PBSCT) in patients with advanced CTCL who might otherwise benefit from this approach. The risk of TRM related to conditioning can be circumvented at least partially by using a reduced-intensity condit
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Current Primary Outcome: The primary goal is to find the minimal dose of conditioning regimen (of the two considered) which will establish engraftment in greater than 80% of patients.

Original Primary Outcome:

Current Secondary Outcome: Assess donor-host chimerism in various hematopoietic and lymphoid cells, dx response, incidence of acute/chronic GVHD, graft failure, assessment of lymphoid subset reconstitution, transplant related morbidity/mortality and dx-free and survival.

Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: October 3, 2002
Date Started: July 30, 2002
Date Completion: December 30, 2017
Last Updated: May 12, 2017
Last Verified: March 31, 2017