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NCT Number: NCT00006251

Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer

This clinical trial studies fludarabine phosphate, low-dose total-body irradiation, and donor stem cell transplant followed by cyclosporine, mycophenolate mofetil, and donor lymphocyte infusion in treating patients with hematopoietic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and total body irradiation (TBI) before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also keep the patient's immune response from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

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Key information

Conditions

Acute Undifferentiated Leukemia Adenocarcinoma Adult Nasal Type Extranodal NK/T-cell Lymphoma Amyloidosis Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Blood Protein Disorders Bone Marrow Diseases Burkitt Lymphoma Carcinoma Carcinoma, Renal Cell Cardiovascular Diseases Childhood Burkitt Lymphoma Childhood Diffuse Large Cell Lymphoma Childhood Grade III Lymphomatoid Granulomatosis Childhood Immunoblastic Large Cell Lymphoma Childhood Myelodysplastic Syndromes Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Disease Chronic Myelomonocytic Leukemia 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 Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Hematologic Diseases 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 Kidney Diseases Kidney Neoplasms 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 Male Urogenital Diseases Mast Cell Activation Disorders Mast Cell Leukemia Mastocytosis Mastocytosis, Systemic Metabolic Diseases Multiple Myeloma Mycosis Fungoides Myelodysplastic-Myeloproliferative Diseases Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Myeloid/NK-cell Acute Leukemia Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial 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 Renal Cell Cancer Recurrent Small Lymphocytic Lymphoma Recurrent/Refractory Childhood Hodgkin Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Hairy Cell Leukemia Refractory Multiple Myeloma Sezary Syndrome 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 Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms 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

Phase 1 / Phase 2

Primary location

University of Torino, Torino, Italy

Loading trial locations.

About this study

PRIMARY OBJECTIVES:

I. To estimate the risk of graft rejection associated with the addition of fludarabine (fludarabine phosphate) to a non-myeloablative conditioning regimen for patients with malignant diseases treatable by allogeneic stem cell transplantation and compare this rate to that observed among patients previously treated without fludarabine.

II. To estimate the rate of grade acute II/IV graft-vs-host disease (GVHD) and chronic GVHD in patients treated with low-dose total-body irradiation (TBI), fludarabine, peripheral blood stem cell (PBSC) infusion and immunosuppression with cyclosporine and mycophenolate mofetil.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days - 4 to -2 and undergo low-dose TBI on day 0. (Note: Patients who have had an autologous transplant within 90 days prior to day 0 will not receive fludarabine phosphate.)

PBSC INFUSION: Patients undergo allogeneic PBSC transplant on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 35 with a taper to day 56. Patients receive mycophenolate mofetil PO BID on days 0-27.

POST TRANSPLANT DONOR LYMPHOCYTE INFUSION (DLI): Patients with stable mixed chimerism on day 56, and without evidence of GVHD, undergo DLI IV over 30 minutes on day 65. Patients without a complete response, full donor chimerism, and GVHD after 2 months undergo further DLI at higher cell numbers. Up to 6 DLIs may be given 65 days apart.

After completion of study treatment, patients are followed up at 4, 6, 12, 18 and 24 months and then annually thereafter.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Patients aged > 49 years and < 75 years with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma who are not eligible for a curative autologous transplantation or who have failed prior autologous transplantation; patients with NHL and 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, 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
  • Renal cell carcinoma
  • Patients with other malignancies declining standard allografts may be approved for transplant following presentation and approval by the Fred Hutchinson Cancer Research Center (FHCRC) chimerism group
  • DONOR:
  • Human leukocyte antigen (HLA) genotypically or phenotypically identical related donor
  • Donor must consent to granulocyte colony-stimulating factor (G-CSF) administration and leukopheresis
  • Donor must have adequate veins for leukopheresis or agree to placement of central venous catheter (femoral, subclavian)
  • Age < 75 years

Exclusion criteria

  • Eligible for a high-priority curative autologous transplant
  • Patients with rapidly progressive aggressive NHL unless in minimal disease state
  • Active 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%
  • Severe defects in pulmonary function testing (defects are currently categorized as mild, moderate and severe) as defined by the pulmonary consultant, or receiving supplementary continuous oxygen
  • Total bilirubin > 2 x the upper limit of normal
  • Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) 4 x the upper limit of normal
  • Karnofsky score < 50
  • Patients with poorly controlled hypertension
  • 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
  • DONOR:
  • Identical twin
  • Age less than 12 years
  • Pregnancy
  • Infection with HIV
  • Inability to achieve adequate venous access
  • Known allergy to G-CSF
  • Current serious systemic illness

Treatment and study plan

total-body irradiation

Radiation

Undergo TBI

Other names: TBI

fludarabine phosphate

Drug

Given IV

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

cyclosporine

Drug

Given PO

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

Mycophenolate mofetil

Drug

Given PO

Other names: Cellcept, MMF

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation

Procedure

Undergo allogeneic PBSC transplant

Donor Lymphocytes

Biological

Undergo DLI

peripheral blood stem cell transplantation

Procedure

Undergo allogeneic PBSC transplant

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

laboratory biomarker analysis

Other

Correlative studies

Primary outcomes

  1. Risk of graft rejection defined as the absence of detectable peripheral blood donor T cells with the addition of fludarabine phosphate

    Time frame: Up to day 56

  2. Incidence of acute grade II/IV GVHD

    Time frame: Up to day 90 after the last DLI

  3. Incidence of chronic GVHD

    Time frame: Up to 24 months

Secondary outcomes

  1. Incidence of myelosuppression (ANC < 500/ul for > 2 days, platelets < 20,000/ul for > 2 days) after initial PBSC infusion

    Time frame: Up to day 56

  2. Response of malignancy to DLI

    Time frame: Up to 24 months

  3. Incidence of aplasia after DLI

    Time frame: Up to 24 months

  4. Dose of CD3+ cells required to convert mixed to full lymphoid chimeras

    Time frame: Up to 24 months

  5. Incidence of non-relapse mortality

    Time frame: Up to 24 months

Sponsors and collaborators

Lead sponsor

Fred Hutchinson Cancer Center

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study title

Induction of Mixed Hematopoietic Chimerism in Patients Using Fludarabine, Low Dose TBI, PBSC Infusion and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil

Important dates

Study start
2000
Primary completion
2005
First posted
Jun 9, 2004
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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