Acute Myeloid Leukemia/Transient Myeloproliferative DisorderNCT00014235
Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies
A study testing fludarabine phosphate, total-body irradiation and peripheral blood stem cell transplantation in people with Acute Myeloid Leukemia/Transient Myeloproliferative Disorder and Acute Undifferentiated Leukemia, run by Fred Hutchinson Cancer Center at 11 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 74 years
- Conditions the study is for
- Acute Myeloid Leukemia/Transient Myeloproliferative Disorder, Acute Undifferentiated Leukemia, Adult Acute Lymphoblastic Leukemia in Remission
- What is being tested?
- fludarabine phosphate, total-body irradiation and peripheral blood stem cell transplantation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 11 sitesin 3 countries
- Study dates
- Dec 2000to Feb 2005
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 74 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
United States9 sites
Baylor University Medical Center
Dallas, Texas, 75246
City of Hope Medical Center
Duarte, California, 91010
Froedtert Hospital
Milwaukee, Wisconsin, 53226-3596
OHSU Knight Cancer Institute
Portland, Oregon, 97239
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
LDS Hospital
Salt Lake City, Utah, 84143
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
Stanford University Hospitals and Clinics
Stanford, California, 94305
University of Arizona Health Sciences Center
Tucson, Arizona, 85724
About this study
Official title: Nonmyeloablative PBSC Allografting From HLA Matched Related Donors Using Fludarabine and/or Low Dose TBI With Disease-Risk Based Immunosuppression
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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.
- Conditions
- 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)
- Being tested
- fludarabine phosphate, total-body irradiation, peripheral blood stem cell transplantation, allogeneic hematopoietic stem cell transplantation, cyclosporine
- Medical subject headings
- Leukemia, Myeloid, Acute, Myeloproliferative Syndrome, Transient, Leukemia, Biphenotypic, Acute, Congenital Abnormalities, Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Blastic Plasmacytoid Dendritic Cell Neoplasm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called 2-F-ara-AMP, Beneflur, Fludara
Given IV
total-body irradiationRadiation
Also called TBI
Undergo TBI
peripheral blood stem cell transplantationProcedure or surgery
Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Undergo PBSCT
allogeneic hematopoietic stem cell transplantationProcedure or surgery
Undergo PBSCT
cyclosporineDrug
Also called ciclosporin, cyclosporin, cyclosporin A, CYSP
Given PO or IV
Also called Cellcept, MMF
Given IV or PO
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (indolent disease) | Experimental | 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. Receives: Drug: fludarabine phosphate; Radiation: total-body irradiation; Procedure: peripheral blood stem cell transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Drug: cyclosporine; Drug: mycophenolate mofetil; Other: laboratory biomarker analysis |
| Arm II (aggressive disease) | Experimental | 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. Receives: Drug: fludarabine phosphate; Radiation: total-body irradiation; Procedure: peripheral blood stem cell transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Drug: cyclosporine; Drug: mycophenolate mofetil; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Probability of severe (grade III/IV) GVHD in each arm
95% confidence interval will be calculated.
Measured: Up to day 84
Probability of severe (grade III/IV) GVHD in each arm
95% confidence intervals will be calculated.
Measured: Up to 5 years
Secondary outcomes (8)
Incidence of graft rejection
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.
Measured: Day 28
Incidence of graft rejection
Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.
Measured: Day 56
Incidence of graft rejection
Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.
Measured: Day 84
Incidence of graft rejection
Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.
Measured: Day 180
Incidence of graft rejection
Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.
Measured: Day 365
Incidence of non-relapse mortality
Examined and reported in a descriptive manner. Confidence intervals will be presented.
Measured: Up to 5 years
Incidence of infectious complications
Examined and reported in a descriptive manner. Confidence intervals will be presented.
Measured: Up to 5 years
Severity of infectious complications
Examined and reported in a descriptive manner. Confidence intervals will be presented.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startDec 2000
- Primary completionFeb 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia/Transient Myeloproliferative DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Maloney, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00014235
- Sponsor's protocol ID
- 1596.00
- Other IDs
- NCI-2012-00671, 1596.00, P30CA015704
- Status last verified
- Jan 2020
- First submitted
- 10 Apr 2001
- Last updated
- 21 Jan 2020
- Results posted
- No
Publications
Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.
PubMed 32499241