Trial record 15 of 93 for:    Open Studies | "Epstein-Barr Virus Infections"

Autologous Stem Cell Transplant Followed By Donor Stem Cell Transplant In Treating Patients With Relapsed or Refractory Lymphoma

This study is currently recruiting participants.
Verified March 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00005803
First received: June 2, 2000
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

This phase I/II trial is studying how well giving autologous stem cell transplant followed by donor stem cell transplant works in treating patients with relapsed or refractory lymphoma. Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect).


Condition Intervention Phase
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Childhood Burkitt Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Prolymphocytic Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Childhood Grade III Lymphomatoid Granulomatosis
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Splenic Marginal Zone Lymphoma
Waldenström Macroglobulinemia
Procedure: peripheral blood stem cell transplantation
Drug: cyclophosphamide
Radiation: total-body irradiation
Drug: carmustine
Drug: etoposide
Drug: cytarabine
Drug: melphalan
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Drug: cyclosporine
Procedure: autologous hematopoietic stem cell transplantation
Biological: therapeutic autologous lymphocytes
Phase 1
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 I/II Study of Autologous Stem Cell Transplantation Followed by Nonmyeloablative Allogeneic Stem Cell Transplantation for Patients With Relapsed or Refractory Lymphoma - A Multi-Center Trial

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Engraftment of HLA identical PBSC allografts [ Time Frame: Day 56 ] [ Designated as safety issue: Yes ]
    The rates and accompanying confidence intervals associated with failure of engraftment at day +56 will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease).

  • Non-relapse mortality [ Time Frame: Day 100 post-non-myeloablative allografting following mobilization and high-dose chemotherapy with autografting ] [ Designated as safety issue: No ]
    The rates and accompanying confidence intervals associated with transplant-related mortality will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease).


Secondary Outcome Measures:
  • Disease-free survival and overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Though progression-free survival (PFS) and overall survival (OS) will be analyzed for the trial as a whole, chemosensitive and chemoresistant patients will be analyzed separately for PFS and OS for comparison to their respective historical controls. These groups will be looked at separately to gather preliminary data on whether or not there appears to be a difference in the PFS among patients who had chemosensitive vs chemoresistant disease.


Estimated Enrollment: 80
Study Start Date: September 1999
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (tandem transplantation)
See Detailed Description
Procedure: peripheral blood stem cell transplantation
Undergo allogeneic transplantation
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Radiation: total-body irradiation
Undergo radiotherapy
Other Name: TBI
Drug: carmustine
Given IV
Other Names:
  • BCNU
  • BiCNU
  • bis-chloronitrosourea
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo allogeneic transplantation
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Drug: mycophenolate mofetil
Given IV
Other Names:
  • Cellcept
  • MMF
Drug: cyclosporine
Given PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous transplantation
Biological: therapeutic autologous lymphocytes
IV donor lymphocyte infusion
Other Names:
  • AL
  • Autologous Lymphocytes
  • autologous T cells

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate engraftment of human leukocyte antibody (HLA) identical peripheral blood stem cell (PBSC) allografts given after conditioning with total-body irradiation (TBI) (200cGy) +/- fludarabine, 90 mg/m^2 and post-grafting immunosuppression with cyclosporine (CSP)/mycophenolate mofetil (MMF) in refractory or relapsed lymphoma patients following an initial autologous peripheral blood stem cell transplant (PBSCT) for disease cytoreduction.

II. To determine the non-relapse mortality at day 100 post-non-myeloablative allografting following mobilization and high-dose chemotherapy with autografting.

SECONDARY OBJECTIVES:

I. To determine the disease free survival and overall survival of non-myeloablative allografting following autologous PBSCT.

OUTLINE:

CONDITIONING REGIMEN: Patients with matched, related stem cell donors receive cyclophosphamide intravenously (IV) on days -6 and -5 and undergo TBI twice daily (BID) on days -3 to -1. Patients with matched, unrelated stem cell donors receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, and cytarabine IV over 3 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2.

TRANSPLANTATION: All patients undergo autologous PBSCT on day 0.

NON-MYELOABLATIVE CONDITIONING: Beginning 40-120 days following PBSC transplant, patients with related donors undergo TBI on day 0. Patients with unrelated donors receive fludarabine IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.

TRANSPLANTATION: Patients undergo non-myeloablative allogeneic PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) BID on days -3 to 56 (patients with related donors) or 100 (patients with unrelated donors) followed by taper to day 180. Patients also receive mycophenolate mofetil PO BID on days 0-27 (patients with related donors) or thrice daily (TID) on days 0-27, then BID on days 28-40 followed by taper to day 96 (patients with unrelated donors).

Some patients may undergo donor lymphocyte infusion if there is evidence of disease progression and no evidence of graft-vs-host disease (GVHD).

After completion of study treatment, patients are followed up at 1, 1.5, 2, and 3 years and then annually thereafter.

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with lymphoma (non-Hodgkin lymphoma [NHL], chronic lymphocytic leukemia/small lymphocytic lymphoma [CLL/SLL] or Hodgkin lymphoma) with primary refractory or relapsed disease after standard chemotherapy at high risk of relapse with conventional autografting; patients with a diagnosis of CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL
  • Must have an HLA genotypically or phenotypically identical related donor or, at a minimum, a high likelihood of identifying an HLA-matched unrelated donor; the determination of availability of a suitable unrelated donor may be based on a World-Book search
  • Cross-over to other tandem autologous-allogeneic research protocol (#2241) will be allowed if the patient loses the suitable HLA-matched related or unrelated donor but has an available HLA-haploidentical donor before receiving the allogeneic transplantation and if the patient meets the eligibility criteria of the subsequent study
  • Cross-over from other tandem autologous-allogeneic research protocol (#2241) will be allowed if a suitable HLA-matched related or unrelated donor is identified before receiving the allogeneic transplantation and if the patient meets the eligibility criteria of the subsequent study
  • Signed informed consent
  • Detectable tumor on radiographic studies or bone marrow biopsy prior to mobilization regimen
  • Expected survival >= 3 months from study entry
  • DONOR: HLA genotypically or phenotypically identical related donor
  • DONOR: must consent to granulocyte-colony stimulating factor (G-CSF) (filgrastim) administration and leukapheresis for both PBSC allograft and subsequent donor lymphocyte infusion (DLI)
  • DONOR: must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral or subclavian)
  • DONOR: Age < 75 yrs, older donors may be considered after review at Patient Care Conference
  • DONOR: Fred Hutchinson Cancer Research Center (FHCRC) matching allowed will be Grades 1.0 to 2.1; unrelated donors who are prospectively: Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
  • DONOR: Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results; a positive anti-donor cytotoxic crossmatch is an absolute donor exclusion
  • DONOR: patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed
  • DONOR: Only G-CSF mobilized peripheral blood mononuclear cells (PBMC) only will be permitted as a hematopoietic stem cell (HSC) source on this protocol

Exclusion Criteria:

  • Life expectancy severely limited by disease other than lymphoma
  • Prior autologous hematopoietic stem cell transplant
  • Patients at high risk of veno-occlusive disease of the liver (criteria not yet rigorously defined but includes bilirubin > 2.0 mg and serum glutamic oxaloacetic transaminase [SGOT] or serum glutamic pyruvate transaminase [SGPT] > 2 x normal); patients may be accepted outside of this range if cleared by gastrointestinal (GI) consult
  • Cardiac ejection fraction (EF) < 40% on multi-gated acquisition (MUGA) scan or cardiac echo (or if unable to obtain ejection fraction, shortening fraction of < 26%); patients with active or a history of cardiac disease should be evaluated with appropriate cardiac studies and/or consult; ejection fraction is required if age > 50 years or there is a history of anthracyclines or history of cardiac disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist
  • Baseline serum-creatinine > 2.0 mg/dl and a calculated or measured creatinine clearance of < 50 ml/minute
  • Seropositive for the human immunodeficiency virus (HIV)
  • Pulmonary dysfunction as measured by a corrected diffusing capacity of the lung for carbon monoxide (DLCO) < 50% of predicted total lung capacity (TLC) < 30%, forced expiratory volume in 1 second (FEV1) < 30% and/or receiving supplementary continuous oxygen; the FHCRC primary investigator (PI) of the study must approve enrollment of all patients with pulmonary nodules
  • Pregnancy or breast-feeding
  • Patients with poorly controlled hypertension despite hypertensive medication
  • Karnofsky score < 60; pediatric criteria: Lansky Play-Performance Score < 40
  • Patients with cluster of differentiation (CD)34 selected auto grafts
  • Patients with active non-hematologic malignancies (except nonmelanoma skin cancers); this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
  • Patients with a history of non-hematologic malignancies (except nonmelanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
  • DONOR: Identical twin
  • DONOR: Age less than 12 years
  • DONOR: Pregnancy
  • DONOR: Human immunodeficiency virus (HIV) seropositivity
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to G-CSF
  • DONOR: Current serious systemic illness
  • DONOR: Failure to meet FHCRC criteria for stem cell donation
  • DONOR: Donor (or centers) who will exclusively donate marrow
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005803

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: David G. Maloney    206-667-5616      
Principal Investigator: David G. Maloney         
VA Puget Sound Health Care System Recruiting
Seattle, Washington, United States, 98101
Contact: Thomas R. Chauncey    206-762-1010      
Principal Investigator: Thomas R. Chauncey         
Germany
Universitaet Leipzig Completed
Leipzig, Germany, D-04103
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: David Maloney Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00005803     History of Changes
Other Study ID Numbers: 1409.00, NCI-2010-00130, 1409.00, P30CA015704, P01CA078902
Study First Received: June 2, 2000
Last Updated: March 3, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Epstein-Barr Virus Infections
Burkitt Lymphoma
Hodgkin Disease
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Prolymphocytic
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Mantle-Cell
Herpesviridae Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on April 17, 2014