Reduced-Intensity Regimen Before Allogeneic Transplant for Patients With Relapsed Non-Hodgkin's or Hodgkin's Lymphoma
- Conditions
- Lymphoma
- Interventions
- Procedure: Extracorporeal PhotopheresisRadiation: Total body irradiation (TBI)Procedure: Allogeneic bone marrow transplantation
- Registration Number
- NCT00057954
- Lead Sponsor
- Eastern Cooperative Oncology Group
- Brief Summary
RATIONALE: Photopheresis allows patient white blood cells to be treated with ultraviolet (UV) light and drugs outside the body to inactivate T cells. Pentostatin may suppress the immune system and reduce the chance of developing graft-versus-host disease (GVHD) following bone marrow transplantation. Combining photopheresis with pentostatin and total-body irradiation may be effective in killing cancer cells before bone marrow transplantation.
PURPOSE: This phase II trial is studying how well giving photophoresis together with pentostatin and total-body irradiation as a reduced-intensity regimen before allogeneic bone marrow transplantation works in treating patients with relapsed non-Hodgkin's or Hodgkin's lymphoma.
- Detailed Description
OBJECTIVES:
* Determine the rate of stable engraftment of donor cells in patients with relapsed non-Hodgkin's or Hodgkin's lymphoma treated with a reduced toxicity conditioning regimen followed by allogeneic (sibling or unrelated) bone marrow transplantation.
* Determine the extent and duration of acute and chronic graft-versus-host disease in patients treated with this regimen.
* Determine the 100-day overall survival and long-term progression-free survival of patients treated with this regimen.
* Evaluate the feasibility of collection of molecular chimerism studies at baseline, days 30, 100, 6 months and one and two years and at relapse.
OUTLINE: This is a multicenter study.
* Conditioning regimen: Patients undergo extracorporeal photopheresis using methoxsalen and UV light on 2 consecutive days between days -7 to -4. Patients receive pentostatin intravenously (IV) continuously on days -3 to -2 and undergo total body irradiation on day -1.
* Allogeneic bone marrow transplantation: Patients undergo infusion of allogeneic bone marrow or stem cells on day 0.
* Graft-versus-host disease prophylaxis: Patients receive oral or IV cyclosporine beginning on day -1 and continuing until 6 months after transplantation, oral mycofenolate mofetil beginning on day 100 and continuing for 1 year, and methotrexate IV on days 1 and 3.
Patients are followed at day 100, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.
PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study within 1.8 years.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 6
- Non-Hodgkin's or Hodgkin's lymphoma that has relapsed following either a course of high dose chemotherapy or autologous stem cell transplantation.
- >= 90 days from prior transplant.
- Have a suitable human leukocyte antigen (HLA)-matched related bone marrow donor or a compatible matched unrelated bone marrow donor by molecular typing at HLA A, B, C, D, DR.
- Physically and psychologically capable of undergoing bone marrow transplantation and its attendant period of strict isolation.
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Be able to receive 400 cGy Total Body Irradiation (TBI).
- Pulmonary function tests: Diffusing capacity or Transfer factor of the lung for carbon monoxide (DLCO) >= 50% predicted, the forced expiratory volume in 1 second (FEV1) >= 50% predicted.
- Left ventricular ejection fraction (LVEF) at least 45% by Multi Gated Acquisition Scan (MUGA) or echocardiogram.
- Renal function: creatinine clearance > 50 ml/min.
- Liver function tests: < 3 x Upper Limit of Normal (ULN). Liver function test include serum glutamic oxaloacetic transaminase (SGOT) (Aspartate transaminase (AST)), Serum Glutamic Pyruvate Transaminase (SGPT) (Alanine transaminase (ALT)), and bilirubin.
- Human immunodeficiency virus positive (HIV+) patients (test positive for P21 antibodies to HIV).
- Evidence of active infection (have received parenteral antibiotics <= 2 weeks prior to registration).
- Pregnant or breast-feeding women.
- Curable with any other therapeutic interventions.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Transplant Cyclosporin (CSA) Reduced toxicity conditioning regimen followed by allogeneic sibling or unrelated transplant. The conditioning regimen includes Extracorporeal Photopheresis, Pentostatin and total body irradiation (TBI). After allogeneic bone marrow transplantation, cyclosporin, mycophenolate mofetil (MMF), and methotrexate (MTX) will be given to prevent graft-versus-host disease (GVHD). Transplant Extracorporeal Photopheresis Reduced toxicity conditioning regimen followed by allogeneic sibling or unrelated transplant. The conditioning regimen includes Extracorporeal Photopheresis, Pentostatin and total body irradiation (TBI). After allogeneic bone marrow transplantation, cyclosporin, mycophenolate mofetil (MMF), and methotrexate (MTX) will be given to prevent graft-versus-host disease (GVHD). Transplant Methotrexate (MTX) Reduced toxicity conditioning regimen followed by allogeneic sibling or unrelated transplant. The conditioning regimen includes Extracorporeal Photopheresis, Pentostatin and total body irradiation (TBI). After allogeneic bone marrow transplantation, cyclosporin, mycophenolate mofetil (MMF), and methotrexate (MTX) will be given to prevent graft-versus-host disease (GVHD). Transplant Allogeneic bone marrow transplantation Reduced toxicity conditioning regimen followed by allogeneic sibling or unrelated transplant. The conditioning regimen includes Extracorporeal Photopheresis, Pentostatin and total body irradiation (TBI). After allogeneic bone marrow transplantation, cyclosporin, mycophenolate mofetil (MMF), and methotrexate (MTX) will be given to prevent graft-versus-host disease (GVHD). Transplant Mycophenolate mofetil (MMF) Reduced toxicity conditioning regimen followed by allogeneic sibling or unrelated transplant. The conditioning regimen includes Extracorporeal Photopheresis, Pentostatin and total body irradiation (TBI). After allogeneic bone marrow transplantation, cyclosporin, mycophenolate mofetil (MMF), and methotrexate (MTX) will be given to prevent graft-versus-host disease (GVHD). Transplant Total body irradiation (TBI) Reduced toxicity conditioning regimen followed by allogeneic sibling or unrelated transplant. The conditioning regimen includes Extracorporeal Photopheresis, Pentostatin and total body irradiation (TBI). After allogeneic bone marrow transplantation, cyclosporin, mycophenolate mofetil (MMF), and methotrexate (MTX) will be given to prevent graft-versus-host disease (GVHD). Transplant Pentostatin Reduced toxicity conditioning regimen followed by allogeneic sibling or unrelated transplant. The conditioning regimen includes Extracorporeal Photopheresis, Pentostatin and total body irradiation (TBI). After allogeneic bone marrow transplantation, cyclosporin, mycophenolate mofetil (MMF), and methotrexate (MTX) will be given to prevent graft-versus-host disease (GVHD).
- Primary Outcome Measures
Name Time Method Proportion of Participants With Successful Engraftment Assessed daily during inpatient stay
- Secondary Outcome Measures
Name Time Method 100-day Overall Survival Assessed at least twice a week for the first 60 days and weekly until day 100. Proportion of patients who survived 100 days or more after enrolled on the study
Progression-free Survival Assessed day 100 post transplant and every 3 months during year 1, every 6 months during years 2-3, then every 12 months during years 4-5 or through diagnosis of disease progression Progression-free survival was defined as time from enrollment to disease progression or death from any cause, whichever occurred first. Patients who did not have progression-free survival events were censored at last date of disease assessment.
Trial Locations
- Locations (19)
St. Mary - Corwin Regional Medical Center
🇺🇸Pueblo, Colorado, United States
Tufts-NEMC Cancer Center
🇺🇸Boston, Massachusetts, United States
Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Swedish Medical Center
🇺🇸Englewood, Colorado, United States
Aurora Presbyterian Hospital
🇺🇸Aurora, Colorado, United States
Porter Adventist Hospital
🇺🇸Denver, Colorado, United States
Presbyterian - St. Luke's Medical Center
🇺🇸Denver, Colorado, United States
St. Joseph Hospital
🇺🇸Denver, Colorado, United States
Rose Medical Center
🇺🇸Denver, Colorado, United States
CCOP - Colorado Cancer Research Program
🇺🇸Denver, Colorado, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Boulder Community Hospital
🇺🇸Boulder, Colorado, United States
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
🇺🇸Grand Junction, Colorado, United States
Sky Ridge Medical Center
🇺🇸Lone Tree, Colorado, United States
North Suburban Medical Center
🇺🇸Thornton, Colorado, United States
Hope Cancer Care Center at Longmont United Hospital
🇺🇸Longmont, Colorado, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Penrose Cancer Center at Penrose Hospital
🇺🇸Colorado Springs, Colorado, United States