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NCT Number: NCT00014235

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

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.

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Key information

Conditions

Acute Myeloid Leukemia/Transient Myeloproliferative Disorder Acute Undifferentiated Leukemia Adult Acute Lymphoblastic 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 Acute Myeloid Leukemia in Remission Adult Nasal Type Extranodal NK/T-cell Lymphoma Amyloidosis Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Blastic Plasmacytoid Dendritic Cell Neoplasm Blood Protein Disorders Bone Marrow Diseases Burkitt Lymphoma Cardiovascular Diseases 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 Disease Chronic Myelomonocytic Leukemia Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cutaneous B-cell Non-Hodgkin Lymphoma DNA Virus Infections Dendritic Cell Sarcoma, Interdigitating Disease Attributes Epstein-Barr Virus Infections Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Eye Neoplasms Hematologic Diseases Hematologic Neoplasms Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Hepatosplenic T-cell Lymphoma Herpesviridae Infections Histiocytic Disorders, Malignant Histiocytosis Hodgkin Disease Immune System Diseases Immunoblastic Lymphadenopathy Immunoglobulin Light-chain Amyloidosis Immunoproliferative Disorders Infections Intraocular Lymphoma Juvenile Myelomonocytic Leukemia Leukemia Leukemia, B-Cell Leukemia, Biphenotypic, Acute Leukemia, Hairy Cell Leukemia, Large Granular Lymphocytic Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia, Mast-Cell Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Leukemia, T-Cell Lymphadenopathy Lymphatic Diseases 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 Lymphoma, Non-Hodgkin Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoma, T-Cell, Peripheral Lymphoproliferative Disorders Mast Cell Activation Disorders Mast Cell Leukemia Mastocytosis Mastocytosis, Systemic Metabolic Diseases Multiple Myeloma Mycosis Fungoides Myelodysplastic-Myeloproliferative Diseases Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Myeloproliferative Disorders Myeloproliferative Syndrome, Transient Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Plasma Cell Nodal Marginal Zone B-cell Lymphoma Noncutaneous Extranodal Lymphoma Nutritional and Metabolic Diseases Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Peripheral T-cell Lymphoma Post-transplant Lymphoproliferative Disorder Precursor Cell Lymphoblastic Leukemia-Lymphoma Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Previously Treated Myelodysplastic Syndromes Primary Systemic Amyloidosis Proteostasis Deficiencies Recurrence 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 Sezary Syndrome Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Small Intestine Lymphoma Splenic Marginal Zone Lymphoma Stage II Multiple Myeloma Stage III Multiple Myeloma T-cell Large Granular Lymphocyte Leukemia Testicular Lymphoma Tumor Virus Infections Untreated Adult Acute Lymphoblastic Leukemia Untreated Adult Acute Myeloid Leukemia Untreated Childhood Acute Lymphoblastic Leukemia Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies Vascular Diseases Virus Diseases Waldenstrom Macroglobulinemia Waldenström Macroglobulinemia de Novo Myelodysplastic Syndromes

Age range

Up to 74 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Universitaet Leipzig, Leipzig, Germany

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

fludarabine phosphate

Drug

Given IV

Other names: 2-F-ara-AMP, Beneflur, Fludara

total-body irradiation

Radiation

Undergo TBI

Other names: TBI

peripheral blood stem cell transplantation

Procedure

Undergo PBSCT

Other names: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

allogeneic hematopoietic stem cell transplantation

Procedure

Undergo PBSCT

cyclosporine

Drug

Given PO or IV

Other names: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune

Mycophenolate mofetil

Drug

Given IV or PO

Other names: Cellcept, MMF

laboratory biomarker analysis

Other

Correlative studies

Primary outcomes

  1. Probability of severe (grade III/IV) GVHD in each arm

    Time frame: Up to day 84

    95% confidence interval will be calculated.

  2. Probability of severe (grade III/IV) GVHD in each arm

    Time frame: Up to 5 years

    95% confidence intervals will be calculated.

Secondary outcomes

  1. Incidence of graft rejection

    Time frame: Day 28

    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.

  2. Incidence of graft rejection

    Time frame: Day 56

    Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.

  3. Incidence of graft rejection

    Time frame: Day 84

    Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.

  4. Incidence of graft rejection

    Time frame: Day 180

    Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.

  5. Incidence of graft rejection

    Time frame: Day 365

    Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.

  6. Incidence of non-relapse mortality

    Time frame: Up to 5 years

    Examined and reported in a descriptive manner. Confidence intervals will be presented.

  7. Incidence of infectious complications

    Time frame: Up to 5 years

    Examined and reported in a descriptive manner. Confidence intervals will be presented.

  8. Severity of infectious complications

    Time frame: Up to 5 years

    Examined and reported in a descriptive manner. Confidence intervals will be presented.

Sponsors and collaborators

Lead sponsor

Fred Hutchinson Cancer Center

Other

Collaborators

  • National Cancer Institute (NCI)
  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Official study title

Nonmyeloablative PBSC Allografting From HLA Matched Related Donors Using Fludarabine and/or Low Dose TBI With Disease-Risk Based Immunosuppression

Important dates

Study start
2000
Primary completion
2005
First posted
Jan 27, 2003
Registry last updated
Jan 21, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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