Reduced-Intensity Regimen Before Allogeneic Transplant for Patients With Relapsed Non-Hodgkin's or Hodgkin's Lymphoma

Study Description

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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.

Condition or disease	Intervention/treatment	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

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	6 participants
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	June 2005
Actual Primary Completion Date :	April 2008
Actual Study Completion Date :	May 2011

Arms and Interventions

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Arm

Intervention/treatment

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: DCF,; 2-Deoxycoformycin,; Nipent; 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: Sandimmune,; cyclosporin A,; CSA,; Neoral,; Gengraf; 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: Cellcept,; mycophenolic acid,; Lilly-68618,; RS-61443,; MMF; 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: Methotrexate sodium,; MTX,; Mexate,; Mexate-AQ,; Folex,; Folex PFS,; Abitrexate,; Rheumatrex,; Amethopterin

Outcome Measures

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Primary Outcome Measures :

1. Proportion of Participants With Successful Engraftment [ Time Frame: Assessed daily during inpatient stay ]

Secondary Outcome Measures :

1. 100-day Overall Survival [ Time Frame: 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
2. 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 ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
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

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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
Porter Adventist Hospital
Denver, Colorado, United States, 80210
Presbyterian - St. Luke's Medical Center
Denver, Colorado, United States, 80218
St. Joseph Hospital
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

National Cancer Institute (NCI)

Investigators

Study Chair:	Francine M. Foss, MD	Yale University

More Information

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Responsible Party:	Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00057954 History of Changes
Other Study ID Numbers:	CDR0000285659; U10CA021115 ( U.S. NIH Grant/Contract ); E1402 ( Other Identifier: Eastern Cooperative Oncology Group (ECOG) )
First Posted:	April 9, 2003
Results First Posted:	February 8, 2013
Last Update Posted:	February 13, 2013
Last Verified:	February 2013

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:

Lymphoma; Hodgkin Disease; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Methotrexate; Cyclosporine; Cyclosporins; Mycophenolic Acid; Pentostatin; Abortifacient Agents, Nonsteroidal; Abortifacient Agents	Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors; Antifungal Agents; Anti-Infective Agents