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Fludarabine Phosphate, Low-Dose Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00005799
First received: June 2, 2000
Last updated: October 16, 2014
Last verified: October 2014
  Purpose

This clinical trial studies fludarabine phosphate, low-dose total body irradiation, and donor stem cell transplant in treating patients with hematologic malignancies or kidney cancer. Giving chemotherapy drugs, such as fludarabine phosphate, 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. 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 before the transplant and cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.


Condition Intervention
Accelerated Phase Chronic Myelogenous 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)
B-cell Chronic Lymphocytic Leukemia
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Chronic Myelogenous Leukemia
Childhood Myelodysplastic Syndromes
Childhood Renal Cell Carcinoma
Chronic Phase Chronic Myelogenous Leukemia
Clear Cell Renal Cell Carcinoma
de Novo Myelodysplastic Syndromes
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Previously Treated Myelodysplastic Syndromes
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular 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
Relapsing Chronic Myelogenous Leukemia
Splenic Marginal Zone Lymphoma
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
T-cell Large Granular Lymphocyte Leukemia
Type 1 Papillary Renal Cell Carcinoma
Type 2 Papillary Renal Cell Carcinoma
Waldenström Macroglobulinemia
Drug: fludarabine phosphate
Radiation: total-body irradiation
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Procedure: allogeneic bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Biological: therapeutic allogeneic lymphocytes
Drug: cyclosporine
Drug: mycophenolate mofetil
Other: pharmacological study
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Low-Dose TBI and Fludarabine Followed by Unrelated Donor Stem Cell Transplantation for Patients With Hematologic Malignancies and Renal Cell Carcinoma - A Multi-center Trial

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Acute Lymphoblastic Leukemia, Childhood Acute Myelocytic Leukemia Acute Myeloid Leukemia, Adult Acute Myeloid Leukemia, Childhood Acute Non Lymphoblastic Leukemia B-cell Lymphomas Chromophil Renal Cell Carcinoma Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Chronic Myeloproliferative Disorders Clear Cell Renal Cell Carcinoma Cutaneous T-cell Lymphoma Follicular Lymphoma Hairy Cell Leukemia Hodgkin Lymphoma Hodgkin Lymphoma, Childhood Kidney Cancer Large Granular Lymphocyte Leukemia Leukemia, B-cell, Chronic Leukemia, Myeloid Lymphoma, Small Cleaved-cell, Diffuse Lymphosarcoma Multiple Myeloma Mycosis Fungoides Myelodysplastic Syndromes Papillary Renal Cell Carcinoma Renal Cancer Sezary Syndrome Waldenstrom Macroglobulinemia
U.S. FDA Resources

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

Primary Outcome Measures:
  • Establishment of an allograft as defined by stable mixed chimerism or full donor chimerism [ Time Frame: At day 56 ] [ Designated as safety issue: No ]
    Engraftment will be assessed separately among patients who receive bone marrow and patients who receive PBSC. Patients with low-risk and high-risk disease will be assessed separately.


Secondary Outcome Measures:
  • Disease-free survival [ Time Frame: Up to 200 days ] [ Designated as safety issue: No ]
    Will be summarized.

  • Relapse [ Time Frame: Assessed up to 5 years ] [ Designated as safety issue: No ]
    Will be summarized.

  • Disease-related mortality [ Time Frame: Before day 200 ] [ Designated as safety issue: Yes ]
    Will be summarized.

  • Response of malignancy to DLI [ Time Frame: Assessed up to 5 years ] [ Designated as safety issue: No ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.

  • Incidence of myelosuppression [ Time Frame: Greater than 2 days after initial PBSC infusion ] [ Designated as safety issue: Yes ]
    Absolute neutrophil count (ANC) less than 500/ul for more than 2 days, platelets less than 20,000/ul for more than 2 days. Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.

  • Incidence of aplasia after DLI [ Time Frame: Greater than 2 days after initial PBSC infusion ] [ Designated as safety issue: Yes ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.

  • Incidence of grades 2-4 acute GVHD after DLI [ Time Frame: Until day 90 ] [ Designated as safety issue: No ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.

  • Incidence of grades 2-4 acute GVHD after PBSC infusion [ Time Frame: Up to day 177 ] [ Designated as safety issue: No ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.

  • Incidence of grades 2-4 chronic extensive GVHD after DLI [ Time Frame: Assessed up to 5 years ] [ Designated as safety issue: No ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.

  • Dose of CD3+ required to convert mixed to full lymphoid chimeras [ Time Frame: Day 28 post-transplant ] [ Designated as safety issue: No ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.

  • Dose of CD3+ required to convert mixed to full lymphoid chimeras [ Time Frame: Day 56 post-transplant ] [ Designated as safety issue: No ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.

  • Dose of CD3+ required to convert mixed to full lymphoid chimeras [ Time Frame: Day 84 post-transplant ] [ Designated as safety issue: No ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.

  • Incidence of infections [ Time Frame: Assessed up to 5 years ] [ Designated as safety issue: Yes ]
    Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.


Enrollment: 55
Study Start Date: November 1999
Primary Completion Date: July 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, TBI, HSCT)

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

TRANSPLANTATION: Patients undergo allogeneic PBSC or bone marrow transplantation on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO BID on days 0-40 with taper to day 96. Patients with mixed chimerism, persistent or progressive disease, and no evidence of graft-versus-host disease and who have been off immunosuppression for at least 2 weeks undergo DLI over 30 minutes. DLI may be repeated every 65 days for up to 3 doses.

Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Radiation: total-body irradiation
Undergo low-dose TBI
Other Name: TBI
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo nonmyeloablative HSCT
Procedure: allogeneic bone marrow transplantation
Undergo nonmyeloablative allogeneic bone marrow transplantation
Other Names:
  • bone marrow therapy, allogeneic
  • bone marrow therapy, allogenic
  • transplantation, allogeneic bone marrow
  • transplantation, allogenic bone marrow
Procedure: peripheral blood stem cell transplantation
Undergo nonmyeloablative allogeneic PBSC transplantation
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Biological: therapeutic allogeneic lymphocytes
Undergo DLI
Other Name: ALLOLYMPH
Drug: cyclosporine
Given PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: mycophenolate mofetil
Given PO
Other Names:
  • Cellcept
  • MMF
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine whether stable allogeneic engraftment from unrelated hematopoietic stem cell donors can be safely established using a non-myeloablative conditioning regimen in patients with hematologic malignancies and renal cell carcinoma.

SECONDARY OBJECTIVES:

I. To evaluate whether donor lymphocyte infusion (DLI) can be safely used in patients with mixed or full donor chimerism to eliminate persistent or progressive disease.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2. Patients also undergo low-dose total-body irradiation (TBI) on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) or bone marrow transplantation on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO BID on days 0-40 with taper to day 96. Patients with mixed chimerism, persistent or progressive disease, and no evidence of graft-versus-host disease and who have been off immunosuppression for at least 2 weeks undergo DLI over 30 minutes. DLI may be repeated every 65 days for up to 3 doses.

After completion of study treatment, patients are follow-up periodically for 5 years.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 50 years with hematologic malignancies treatable by allogeneic hematopoietic stem cell transplant (HSCT) and all patients with B cell malignancies except those who may be cured by autologous stem cell transplantation (SCT)
  • Age =< 50 years of age with hematologic diseases treatable by allogeneic HSCT who through pre-existing medical conditions or prior therapy are considered to be of high risk for regimen related toxicity associated with a conventional transplant or those patients who refuse a conventional SCT; transplants must be approved for these inclusion criteria by both the participating institution's patient review committee such as the Patient Care Conference (PCC at the Fred Hutchinson Cancer Research Center [FHCRC]) and by the principal investigator
  • Patients with metastatic renal cell carcinoma with the histologic subtypes of clear cell, papillary and medullary may be accepted regardless of age
  • The following diseases will be permitted although other diagnoses can be considered if approved by PCC or the participating institution's patient review committees and the principal investigator

    • Non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), Hodgkin lymphoma (HL) - must have received and failed frontline therapy
    • Multiple myeloma - must have received prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative HSCT is permitted
    • Acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) - must be in complete remission and have received cytotoxic chemotherapy at some stage before transplant; patients with molecular or early relapse will be accepted providing a donor is available; patients with persistent or refractory disease will be considered on a case by case basis and transplants must be approved by the institution's patient review committees
    • Chronic myelogenous leukemia (CML) - patients will be accepted in chronic phase or accelerated phase; patients who have received prior autografts after high dose therapy or have undergone intensive chemotherapy for either peripheral blood stem cell (PBSC) mobilization or treatment of advanced CML may be enrolled provided they are in complete remission (CR), chronic phase (CP) or accelerated phase (AP)
    • Myelodysplastic syndromes (MDS) - all patients with MDS will be eligible for this protocol; however, those patients with MDS and frank AML (> 30% blasts in bone marrow aspirate by morphology or flow cytometry) will require induction chemotherapy to obtain a complete remission (marrow blasts < 5%) and remain in complete remission at time of transplant
    • Renal cell carcinoma- must have evidence of disease not amenable to surgical cure or metastatic disease by radiological and histological criteria
  • DONOR: Human leukocyte antigen (HLA) matched unrelated donor; donors should be matched for HLA -A, -B, -C, -developmentally regulated ribonucleic acid (RNA) binding protein 1(DRB)1 and -class II, DQ beta 1 (DQB) 1; HLA -A and -B loci should be matched at least to the level of resolution; HLA -C, -DRB1, and -DQB1 should be typed at the highest level of resolution available at the time of donor selection; donor must consent to either a bone marrow harvest or PBSC mobilization with filgrastim (G-CSF) arranged through the National Marrow Donor Program (NMDP) or other donor centers

Exclusion Criteria:

  • Patients with rapidly progressive intermediate or high grade NHL
  • Renal cell carcinoma patients with expected survival of less than 6 months

    • Bulky disease resulting in severely limited performance status (< 70%)
    • Any vertebral instability
  • Any 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 with non-hematological tumors
  • Cardiac ejection fraction < 30%
  • Diffusion capacity of the lung for carbon monoxide (DLCO) < 30% and/or receiving supplementary continuous oxygen
  • Significant elevation of bilirubin and transaminases should be discussed at participating institutions' patient review committees in a case by case basis; evidence of synthetic dysfunction or severe cirrhosis will result in patient exclusion
  • Karnofsky score < 50 (except renal cell carcinoma [RCC])
  • Patients with poorly controlled hypertension on multiple antihypertensives
  • Human immunodeficiency virus (HIV) positive patients
  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: NCT00005799

Locations
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, Colorado
University of Colorado
Denver, Colorado, United States, 80217-3364
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
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Germany
Universitaet Leipzig
Leipzig, Germany, D-04103
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Brenda Sandmaier 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: NCT00005799     History of Changes
Other Study ID Numbers: 1463.00, NCI-2012-00667, 1463.00, P01CA018029, P30CA015704
Study First Received: June 2, 2000
Last Updated: October 16, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Hodgkin Disease
Leukemia
Leukemia, Hairy Cell
Leukemia, Large Granular Lymphocytic
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myeloid, Acute
Leukemia, Myeloid, Chronic-Phase
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Multiple Myeloma
Mycosis Fungoides
Myelodysplastic Syndromes
Neoplasms, Plasma Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Sezary Syndrome
Syndrome
Waldenstrom Macroglobulinemia
Adenocarcinoma

ClinicalTrials.gov processed this record on November 27, 2014