Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies
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Purpose
The purpose of this study is to evaluate whether we can get rid of cancer through the use of donor blood cell transplants. New data suggest that a powerful immune effect from donor cells may by itself be an effective type of treatment for some cancers. Stem cells given in the setting of bone marrow transplantation have usually been collected from the donor's bone marrow under general anesthetic. Stem cells move in the blood in very small numbers, but by giving a medicine called granulate colony-stimulating factor (filgrastim [G-CSF]), the bone marrow can release large numbers of stem cells into the blood stream. These stem cells can then be collected by machine and given to the patient. This is called a peripheral blood stem cell (PBSC) transplant. White cells and platelets recover more rapidly after PBSC transplants than with cells taken from the bone marrow. The purpose of this study is to try and develop treatments that get rid of the cancer through a reaction of the immune system
| 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 |
Procedure: peripheral blood stem cell transplantation Procedure: allogeneic hematopoietic stem cell transplantation Radiation: total-body irradiation Drug: fludarabine phosphate Drug: mycophenolate mofetil Drug: cyclosporine |
| 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 |
- Probability of severe (grade III/IV) GVHD in each arm [ Time Frame: Assessed 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: Assessed up to 5 years ] [ Designated as safety issue: Yes ]95% confidence intervals will be calculated.
- 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: Assessed up to 5 years ] [ Designated as safety issue: No ]Examined and reported in a descriptive manner. Confidence intervals will be presented.
- Incidence and severity of infectious complications [ Time Frame: Assessed up to 5 years ] [ Designated as safety issue: Yes ]Examined and reported in a descriptive manner. Confidence intervals will be presented.
| Enrollment: | 159 |
| 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. |
Procedure: peripheral blood stem cell transplantation
Undergo PBSCT
Other Names:
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo PBSCT
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: fludarabine phosphate
Given IV
Other Names:
Drug: mycophenolate mofetil
Given IV or PO
Other Names:
Drug: cyclosporine
Given PO or IV
Other Names:
|
|
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. |
Procedure: peripheral blood stem cell transplantation
Undergo PBSCT
Other Names:
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo PBSCT
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: fludarabine phosphate
Given IV
Other Names:
Drug: mycophenolate mofetil
Given IV or PO
Other Names:
Drug: cyclosporine
Given PO or IV
Other Names:
|
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 |
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 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 glutamic 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| United States, Arizona | |
| University of Arizona | |
| Tucson, Arizona, United States, 85724 | |
| United States, California | |
| City of Hope Medical Center | |
| Duarte, California, United States, 91010 | |
| Stanford University | |
| 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 | |
| University of Utah, Salt Lake City | |
| 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 | |
| Principal Investigator: | David Maloney | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
More Information
No publications provided
| Responsible Party: | Maloney, David, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
| ClinicalTrials.gov Identifier: | NCT00014235 History of Changes |
| Other Study ID Numbers: | 1596.00, NCI-2012-00671, P01CA078902, P01HL036444 |
| Study First Received: | April 10, 2001 |
| Last Updated: | May 31, 2013 |
| Health Authority: | United States: Federal Government |
Additional relevant MeSH terms:
|
Congenital Abnormalities Amyloidosis Burkitt Lymphoma Neoplasms Hodgkin Disease Immunoblastic Lymphadenopathy Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Hairy Cell Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Mast-Cell Leukemia, Myeloid, Acute Leukemia, Myeloid Leukemia, Myelomonocytic, Chronic |
Leukemia, T-Cell Leukemia-Lymphoma, Adult T-Cell Lymphoma Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Lymphomatoid Granulomatosis Lymphoproliferative Disorders Waldenstrom Macroglobulinemia Multiple Myeloma Neoplasms, Plasma Cell Mycoses Mycosis Fungoides Myelodysplastic Syndromes Preleukemia |
ClinicalTrials.gov processed this record on June 18, 2013