Reduced-Intensity Regimen Before Allogeneic Transplant for Patients With Relapsed Non-Hodgkin's or Hodgkin's Lymphoma
This study has been terminated.
(Slow accrual)
Sponsor:
Eastern Cooperative Oncology Group
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00057954
First received: April 7, 2003
Last updated: February 11, 2013
Last verified: February 2013
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Lymphoma |
Procedure: Extracorporeal Photopheresis Drug: Pentostatin Radiation: Total body irradiation (TBI) Procedure: Allogeneic bone marrow transplantation Drug: Cyclosporin (CSA) Drug: Mycophenolate mofetil (MMF) Drug: Methotrexate (MTX) |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplantation for the Treatment of Relapsed Non-Hodgkin and Hodgkin Lymphoma |
Resource links provided by NLM:
Drug Information available for:
Methotrexate
Methotrexate sodium
Mycophenolic acid
Mycophenolate sodium
Pentostatin
Cyclosporine
Cyclosporin
Mycophenolate mofetil hydrochloride
Mycophenolate mofetil
Genetic and Rare Diseases Information Center resources:
Anaplastic Large Cell Lymphoma
B-cell Lymphomas
Burkitt Lymphoma
Chronic Lymphocytic Leukemia
Follicular Lymphoma
Hodgkin Lymphoma
Leukemia, B-cell, Chronic
Leukemia, T-cell, Chronic
Lymphoblastic Lymphoma
Lymphoma, Large-cell
Lymphoma, Large-cell, Immunoblastic
Lymphoma, Small Cleaved-cell, Diffuse
Lymphosarcoma
Mantle Cell Lymphoma
Mycosis Fungoides
Plasmablastic Lymphoma
Sezary Syndrome
Small Non-cleaved Cell Lymphoma
Squamous Cell Carcinoma of the Head and Neck
U.S. FDA Resources
Further study details as provided by Eastern Cooperative Oncology Group:
Primary Outcome Measures:
- Proportion of Participants With Successful Engraftment [ Time Frame: Assessed daily during inpatient stay ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- 100-day Overall Survival [ Time Frame: Assessed at least twice a week for the first 60 days and weekly until day 100. ] [ Designated as safety issue: No ]Proportion of patients who survived 100 days or more after enrolled on the study
- Progression-free Survival [ Time Frame: 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 ] [ Designated as safety issue: No ]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.
| Enrollment: | 6 |
| Study Start Date: | June 2005 |
| Study Completion Date: | May 2011 |
| Primary Completion Date: | April 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Transplant
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).
|
Procedure: Extracorporeal Photopheresis
Day -7 to -4: Extracorporeal Photopheresis may be given as an outpatient therapy on two consecutive days any time between days -7 to -4. This must be performed on UVAR or XTS photopheresis machines (Therakos, Inc.) according to standard procedure as per manufacturer's guidelines.
Other Name: extracorporeal photochemotherapy
Drug: Pentostatin
Day -3, -2: Pentostatin 4 mg/m²/d by continuous IV infusion (Total dose = 8 mg/m²)
Other Names:
Radiation: Total body irradiation (TBI)
Day -1: TBI 400 cGy total dose given in two 200cGy doses. Patients who have received TBI for a previous transplant or radiation as part of previous treatment for a lymphoid malignancy will receive only 200 cGy in 1 dose.
Other Name: radiation therapy
Procedure: Allogeneic bone marrow transplantation
Day 0: Infusion of unmanipulated allogeneic bone marrow or stem cells. Minimum cell dose of 2 x 106 CD34 cells/kg recipient and no more than 10 x 10^6 CD34/kg
Other Name: allogeneic stem cell transplantation
Drug: Cyclosporin (CSA)
Cyclosporin A or tacrolimus will be administered according to institutional GVHD prophylaxis protocols. Therapeutic levels will be maintained and patients will be switched to oral agents when they can tolerate
Other Names:
Drug: Mycophenolate mofetil (MMF)
At day 100 MMF will be introduced at a dose of 250 mg po BID and cyclosporine or tacrolimus will be tapered according to the discretion of the investigator. The dosage will be escalated to a maximum of 2 g/d at the discretion of the attending physician and will be tapered and discontinued at 12 months if there is no active cGVHD. Doses should be given on an empty stomach
Other Names:
Drug: Methotrexate (MTX)
The dose of Methotrexate is based on the corrected ideal body weight for patients with > 33% above ideal weight. Day +1 MTX 15 mg/m² IV push; Day +3 MTX 10 mg/m² IV push (May be omitted if patient develops mouth sores.) Other Names:
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00057954
Please refer to this study by its ClinicalTrials.gov identifier: NCT00057954
Locations
| United States, Colorado | |
| Aurora Presbyterian Hospital | |
| Aurora, Colorado, United States, 80012 | |
| Boulder Community Hospital | |
| Boulder, Colorado, United States, 80301-9019 | |
| Penrose Cancer Center at Penrose Hospital | |
| Colorado Springs, Colorado, United States, 80933 | |
| St. Joseph Hospital | |
| Denver, Colorado, United States, 80218 | |
| Porter Adventist Hospital | |
| Denver, Colorado, United States, 80210 | |
| Presbyterian - St. Luke's Medical Center | |
| Denver, Colorado, United States, 80218 | |
| Rose Medical Center | |
| Denver, Colorado, United States, 80220 | |
| CCOP - Colorado Cancer Research Program | |
| Denver, Colorado, United States, 80224-2522 | |
| Swedish Medical Center | |
| Englewood, Colorado, United States, 80110 | |
| St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center | |
| Grand Junction, Colorado, United States, 81502 | |
| Sky Ridge Medical Center | |
| Lone Tree, Colorado, United States, 80124 | |
| Hope Cancer Care Center at Longmont United Hospital | |
| Longmont, Colorado, United States, 80502 | |
| St. Mary - Corwin Regional Medical Center | |
| Pueblo, Colorado, United States, 81004 | |
| North Suburban Medical Center | |
| Thornton, Colorado, United States, 80229 | |
| United States, Florida | |
| Mayo Clinic - Jacksonville | |
| Jacksonville, Florida, United States, 32224 | |
| United States, Massachusetts | |
| Tufts-NEMC Cancer Center | |
| Boston, Massachusetts, United States, 02111 | |
| United States, Minnesota | |
| Mayo Clinic Cancer Center | |
| Rochester, Minnesota, United States, 55905 | |
| United States, New Jersey | |
| Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School | |
| New Brunswick, New Jersey, United States, 08903 | |
| United States, Ohio | |
| Case Comprehensive Cancer Center | |
| Cleveland, Ohio, United States, 44106-5065 | |
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
| Study Chair: | Francine M. Foss, MD | Yale University |
More Information
No publications provided
| Responsible Party: | Eastern Cooperative Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00057954 History of Changes |
| Other Study ID Numbers: | CDR0000285659, U10CA021115, E1402 |
| Study First Received: | April 7, 2003 |
| Results First Received: | January 7, 2013 |
| Last Updated: | February 11, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by Eastern Cooperative Oncology Group:
|
recurrent adult Hodgkin lymphoma recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult Burkitt lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma |
recurrent mantle cell lymphoma recurrent mycosis fungoides/Sezary syndrome recurrent adult T-cell leukemia/lymphoma anaplastic large cell lymphoma recurrent marginal zone lymphoma recurrent small lymphocytic lymphoma extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone B-cell lymphoma splenic marginal zone lymphoma |
Additional relevant MeSH terms:
|
Hodgkin Disease Lymphoma Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Cyclosporine Cyclosporins Methotrexate Mycophenolate mofetil Mycophenolic Acid Pentostatin Abortifacient Agents |
Abortifacient Agents, Nonsteroidal Adenosine Deaminase Inhibitors Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents Antimetabolites Antimetabolites, Antineoplastic Antineoplastic Agents Antirheumatic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunologic Factors Immunosuppressive Agents Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on February 27, 2015