Brief Title
Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies
Official Title
Nonmyeloablative PBSC Allografting From HLA Matched Related Donors Using Fludarabine and/or Low Dose TBI With Disease-Risk Based Immunosuppression
Brief Summary
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.
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.
Study Type
Interventional
Primary Outcome
Probability of severe (grade III/IV) GVHD in each arm
Secondary Outcome
Incidence of graft rejection
Condition
Acute Myeloid Leukemia/Transient Myeloproliferative Disorder
Intervention
fludarabine phosphate
Study Arms / Comparison Groups
Arm I (indolent disease)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
160
Start Date
December 2000
Primary Completion Date
February 2005
Eligibility Criteria
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
Gender
All
Ages
N/A - 74 Years
Accepts Healthy Volunteers
No
Contacts
David Maloney, ,
Location Countries
Germany
Location Countries
Germany
Administrative Informations
NCT ID
NCT00014235
Organization ID
1596.00
Secondary IDs
NCI-2012-00671
Responsible Party
Sponsor
Study Sponsor
Fred Hutchinson Cancer Research Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Study Sponsor
David Maloney, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Verification Date
January 2020