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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-05-31

Brief Summary

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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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Detailed Description

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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.

Conditions

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Acute Undifferentiated Leukemia Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma 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 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 Myeloid/NK-cell Acute Leukemia 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 Renal Cell Cancer 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 Waldenström Macroglobulinemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (fludarabine phosphate, TBI, PBSC transplant, DLI)

CONDITIONING REGIMEN : Patients receive fludarabine phosphate 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 PO BID on days -3 to 35 with a taper to day 56. Patients receive mycophenolate mofetil PO BID on days 0-27.

POST TRANSPLANT 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.

Group Type EXPERIMENTAL

total-body irradiation

Intervention Type RADIATION

Undergo TBI

fludarabine phosphate

Intervention Type DRUG

Given IV

cyclosporine

Intervention Type DRUG

Given PO

mycophenolate mofetil

Intervention Type DRUG

Given PO

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

Undergo allogeneic PBSC transplant

donor lymphocytes

Intervention Type BIOLOGICAL

Undergo DLI

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Undergo allogeneic PBSC transplant

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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total-body irradiation

Undergo TBI

Intervention Type RADIATION

fludarabine phosphate

Given IV

Intervention Type DRUG

cyclosporine

Given PO

Intervention Type DRUG

mycophenolate mofetil

Given PO

Intervention Type DRUG

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Undergo allogeneic PBSC transplant

Intervention Type PROCEDURE

donor lymphocytes

Undergo DLI

Intervention Type BIOLOGICAL

peripheral blood stem cell transplantation

Undergo allogeneic PBSC transplant

Intervention Type PROCEDURE

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

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TBI 2-F-ara-AMP Beneflur Fludara ciclosporin cyclosporin cyclosporin A CYSP Sandimmune Cellcept MMF PBPC transplantation PBSC transplantation peripheral blood progenitor cell transplantation transplantation, peripheral blood stem cell

Eligibility Criteria

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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

Maximum Eligible Age

74 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No