Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00014235
First received: April 10, 2001
Last updated: December 30, 2013
Last verified: December 2013
  Purpose

This clinical trial studies fludarabine phosphate and total-body radiation followed by donor peripheral blood stem cell transplant and immunosuppression in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving total-body irradiation together with fludarabine phosphate, cyclosporine, and mycophenolate mofetil before transplant may stop this from happening.


Condition Intervention
Acute Myeloid Leukemia/Transient Myeloproliferative Disorder
Acute Undifferentiated Leukemia
Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Blastic Plasmacytoid Dendritic Cell Neoplasm
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Burkitt Lymphoma
Childhood Diffuse Large Cell Lymphoma
Childhood Immunoblastic Large Cell Lymphoma
Childhood Myelodysplastic Syndromes
Childhood Nasal Type Extranodal NK/T-cell Lymphoma
Chronic Myelomonocytic Leukemia
Cutaneous B-cell Non-Hodgkin Lymphoma
de Novo Myelodysplastic Syndromes
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Juvenile Myelomonocytic Leukemia
Mast Cell Leukemia
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Nodal Marginal Zone B-cell Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Post-transplant Lymphoproliferative Disorder
Previously Treated Myelodysplastic Syndromes
Primary Systemic Amyloidosis
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid 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 Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Anaplastic Large Cell 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
Refractory Hairy Cell Leukemia
Refractory Multiple Myeloma
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
T-cell Large Granular Lymphocyte Leukemia
Testicular Lymphoma
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Adult Acute Myeloid Leukemia
Untreated Childhood Acute Lymphoblastic Leukemia
Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
Waldenström Macroglobulinemia
Drug: fludarabine phosphate
Radiation: total-body irradiation
Procedure: peripheral blood stem cell transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Drug: cyclosporine
Drug: mycophenolate mofetil
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Nonmyeloablative PBSC Allografting From HLA Matched Related Donors Using Fludarabine and/or Low Dose TBI With Disease-Risk Based Immunosuppression

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: AL Amyloidosis Acute Lymphoblastic Leukemia Acute Lymphoblastic Leukemia, Childhood Acute Myelocytic Leukemia Acute Myeloid Leukemia, Adult Acute Myeloid Leukemia, Childhood Acute Non Lymphoblastic Leukemia Anaplastic Large Cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Angioimmunoblastic T-cell Lymphoma B-cell Lymphomas Blastic Plasmacytoid Dendritic Cell Burkitt Lymphoma Chronic Lymphocytic Leukemia Chronic Myelomonocytic Leukemia Chronic Myeloproliferative Disorders Cutaneous T-cell Lymphoma Dendritic Cell Tumor Follicular Lymphoma Hairy Cell Leukemia Hodgkin Lymphoma Hodgkin Lymphoma, Childhood Juvenile Myelomonocytic Leukemia Large Granular Lymphocyte Leukemia Leukemia, B-cell, Chronic Leukemia, Myeloid Leukemia, T-cell, Chronic Lymphoblastic Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoma, Small Cleaved-cell, Diffuse Lymphomatoid Granulomatosis Lymphosarcoma Mantle Cell Lymphoma Mastocytosis Multiple Myeloma Mycosis Fungoides Myelodysplastic Syndromes Myelodysplastic/myeloproliferative Disease Peripheral T-cell Lymphoma Plasmablastic Lymphoma Sezary Syndrome Small Non-cleaved Cell Lymphoma Systemic Mastocytosis Waldenstrom Macroglobulinemia
U.S. FDA Resources

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

Primary Outcome Measures:
  • Probability of severe (grade III/IV) GVHD in each arm [ Time Frame: Up to day 84 ] [ Designated as safety issue: Yes ]
    95% confidence interval will be calculated.

  • Probability of severe (grade III/IV) GVHD in each arm [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    95% confidence intervals will be calculated.


Secondary Outcome Measures:
  • Incidence of graft rejection [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Chimerism analysis by fluorescent in situ hybridization (FISH) or variable number tandem repeat (VNTR). Examined and reported in a descriptive manner. Confidence intervals will be presented.

  • Incidence of graft rejection [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
    Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.

  • Incidence of graft rejection [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
    Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.

  • Incidence of graft rejection [ Time Frame: Day 180 ] [ Designated as safety issue: No ]
    Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.

  • Incidence of graft rejection [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
    Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.

  • Incidence of non-relapse mortality [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Examined and reported in a descriptive manner. Confidence intervals will be presented.

  • Incidence of infectious complications [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Examined and reported in a descriptive manner. Confidence intervals will be presented.

  • Severity of infectious complications [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Examined and reported in a descriptive manner. Confidence intervals will be presented.


Estimated Enrollment: 160
Study Start Date: December 2000
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (indolent disease)

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

TRANSPLANTATION: Patients undergo donor PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.

Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Procedure: peripheral blood stem cell transplantation
Undergo PBSCT
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo PBSCT
Drug: cyclosporine
Given PO or IV
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: mycophenolate mofetil
Given IV or PO
Other Names:
  • Cellcept
  • MMF
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (aggressive disease)

CONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I.

TRANSPLANTATION: Patients undergo donor PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.

Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Procedure: peripheral blood stem cell transplantation
Undergo PBSCT
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo PBSCT
Drug: cyclosporine
Given PO or IV
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: mycophenolate mofetil
Given IV or PO
Other Names:
  • Cellcept
  • MMF
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the rate of grade III/IV graft-versus-host disease (GVHD) in patients treated with low-dose total body irradiation (TBI), fludarabine (fludarabine phosphate), PBSC infusion and immunosuppression with mycophenolate mofetil and a disease risk-based cyclosporine taper.

II. To estimate the risk of graft rejection, GVHD, disease response, non-relapse mortality and the incidence and severity of infectious complications using this treatment strategy.

OUTLINE: Patients are assigned to 1 of 2 treatment groups.

ARM I (indolent disease):

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo TBI on day 0.

TRANSPLANTATION: Patients undergo donor peripheral blood stem cell transplantation (PBSCT) on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.

ARM II (aggressive disease):

CONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I.

TRANSPLANTATION: Patients undergo donor PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.

After completion of study treatment, patients are followed up for 5 years.

  Eligibility

Ages Eligible for Study:   up to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or multiple myeloma who are not eligible for a curative autologous transplantation or who have received a prior autologous transplantation; patients with NHL or CLL must have failed prior therapy with an alkylating agent and/or fludarabine, or be at high risk of relapse; patients with multiple myeloma must have stage II or III disease and received prior chemotherapy
  • Patients < 50 years of age with NHL, Hodgkin's disease (HD), CLL or multiple myeloma at high risk of regimen related toxicity through prior autologous transplant or through pre-existing medical conditions
  • Patients < 75 years of age with other malignant diseases treatable by allogeneic bone marrow transplant (BMT) whom through pre-existing chronic disease affecting kidneys, liver, lungs, and heart are considered to be at high risk for regimen related toxicity using standard high dose regimens; the following diseases are the likely candidates

    • Myelodysplastic syndromes
    • Myeloproliferative syndromes
    • Acute Leukemia with < 10% blasts
    • Amyloidosis
    • Hodgkin's disease
  • The Fred Hutchinson Cancer Research Center (FHCRC) Patient Care Conference (PCC) may approve patients with other malignancies or patients declining standard allografts for transplant following presentation and approval; centers outside the FHCRC that have a PCC or equivalent should obtain their Institutional approval; if there is not a comparable group at the Institution, please contact the FHCRC Principal Investigator for FHCRC approval through PCC
  • DONOR: Human leukocyte antigen (HLA) genotypically or phenotypically identical related donor
  • DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis
  • DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)

Exclusion Criteria:

  • Eligible for a high-priority curative autologous transplant
  • Patients with rapidly progressive aggressive NHL unless in minimal disease state
  • Any current central nervous system (CNS) involvement with disease
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Females who are pregnant
  • Patients who are human immunodeficiency virus (HIV) positive
  • Cardiac ejection fraction < 40%; ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease
  • Receiving supplementary continuous oxygen
  • Diffusing capacity of the lung for carbon monoxide (DLCO) < 30%
  • Total lung capacity (TLC) < 30%
  • Forced expiratory volume in one second (FEV1) < 30%
  • Total bilirubin > 2x the upper limit of normal
  • Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) 4x the upper limit of normal
  • Karnofsky score < 50
  • Patients with poorly controlled hypertension who are unable to have blood pressure kept below 150/90 on standard medication
  • Patients with renal failure are eligible, however patients with renal compromise (serum creatinine greater than 2.0) will likely have further compromise in renal function and may require hemodialysis (which may be permanent) due to the need to maintain adequate serum cyclosporine levels
  • The addition of cytotoxic agents for "cytoreduction" with the exception of hydroxyurea and imatinib mesylate will not be allowed within two weeks of the initiation of conditioning
  • DONOR: Identical twin
  • DONOR: Age less than 12 years
  • DONOR: Pregnancy
  • DONOR: Infection with HIV
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to G-CSF
  • DONOR: Current serious systemic illness
  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: NCT00014235

Locations
United States, Arizona
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Stanford University Hospitals and Clinics
Stanford, California, United States, 94305
United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
United States, Utah
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States, 84112
LDS Hospital
Salt Lake City, Utah, United States, 84143
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
United States, Wisconsin
Froedtert Hospital
Milwaukee, Wisconsin, United States, 53226-3596
Germany
Universitaet Leipzig
Leipzig, Germany, D-04103
Italy
University of Torino
Torino, Italy, 10126
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: NCT00014235     History of Changes
Other Study ID Numbers: 1596.00, NCI-2012-00671, 1596.00, P30CA015704
Study First Received: April 10, 2001
Last Updated: December 30, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Amyloidosis
Burkitt Lymphoma
Disease
Down Syndrome
Hodgkin Disease
Immunoblastic Lymphadenopathy
Intraocular Lymphoma
Leukemia
Leukemia, Hairy Cell
Leukemia, Large Granular Lymphocytic
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Mast-Cell
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Leukemoid Reaction
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Mantle-Cell

ClinicalTrials.gov processed this record on November 27, 2014