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

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ClinicalTrials.gov Identifier: NCT00057954
Recruitment Status : Terminated (Slow accrual)
First Posted : April 9, 2003
Results First Posted : February 8, 2013
Last Update Posted : February 13, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group

Tracking Information
First Submitted Date  ICMJE April 7, 2003
First Posted Date  ICMJE April 9, 2003
Results First Submitted Date  ICMJE January 7, 2013
Results First Posted Date  ICMJE February 8, 2013
Last Update Posted Date February 13, 2013
Study Start Date  ICMJE June 2005
Actual Primary Completion Date April 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 11, 2013)
Proportion of Participants With Successful Engraftment [ Time Frame: Assessed daily during inpatient stay ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2013)
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Reduced-Intensity Regimen Before Allogeneic Transplant for Patients With Relapsed Non-Hodgkin's or Hodgkin's Lymphoma
Official Title  ICMJE A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplantation for the Treatment of Relapsed Non-Hodgkin and Hodgkin Lymphoma
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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).
Interventions:
  • 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)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 7, 2013)
6
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE May 2011
Actual Primary Completion Date April 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00057954
Other Study ID Numbers  ICMJE CDR0000285659
U10CA021115 ( U.S. NIH Grant/Contract )
E1402 ( Other Identifier: Eastern Cooperative Oncology Group (ECOG) )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eastern Cooperative Oncology Group
Study Sponsor  ICMJE Eastern Cooperative Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Francine M. Foss, MD Yale University
PRS Account Eastern Cooperative Oncology Group
Verification Date February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP