Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer
Campath (Alemtuzumab) Dose Escalation, Low-Dose TBI and Fludarabine Followed by HLA Class II Mismatched Donor Stem Cell Transplantation for Patients With Hematologic Malignancies: A Multicenter Trial
4 other identifiers
interventional
12
2 countries
2
Brief Summary
This phase II trial is studying the side effects and best dose of alemtuzumab when given together with fludarabine phosphate and total-body irradiation followed by cyclosporine and mycophenolate mofetil in treating patients who are undergoing a donor stem cell transplant for hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, a monoclonal antibody, such as alemtuzumab, and radiation therapy before a donor stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Mar 2005
Longer than P75 for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2005
CompletedFirst Submitted
Initial submission to the registry
July 8, 2005
CompletedFirst Posted
Study publicly available on registry
July 11, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
May 26, 2015
CompletedResults Posted
Study results publicly available
May 30, 2017
CompletedMay 30, 2017
April 1, 2017
5.3 years
July 8, 2005
January 12, 2017
April 25, 2017
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of Grade III-IV Acute GVHD
Severity of Individual Organ Involvement Liver: Stage 2 - bilirubin (3-5.9mg/100ml) Stage 3 - bilirubin (6-14.9mg/100ml) Stage 4 - bilirubin \> 15mg/100ml Gut: Diarrhea is graded stage 1 to stage 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as stage 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall Severity of GVHD Grade III - Stage 2 to 4 gastrointestinal involvement and/or Stage 2 to 4 liver involvement with or without a rash Grade IV - Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
100 days after transplant
Secondary Outcomes (6)
Incidence of Graft Rejection
84 days after transplant
Incidence of High-dose Corticosteroid Utilization.
100 days after transplant
Incidence of Non-relapse Mortality
100 days after transplant
Incidence of Infection
Up to 5 years post-transplant
Immune Reconstitution
Up to 1 year post-transplant
- +1 more secondary outcomes
Study Arms (1)
Treatment (chemotherapy, TBI, transplant)
EXPERIMENTALNONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive alemtuzumab IV over 6 hours once daily on days -6, -5, and -4 OR days -5 and -4 and fludarabine phosphate IV over 30 minutes on days -4, -3, and -2. Patients also undergo low-dose TBI on day 0. ALLOGENEIC PBSCT: After completion of TBI, patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 12 hours on days -3 to 180 followed by a taper until day 365 in the absence of GVHD. Beginning 4-6 hours after completion of allogeneic PBSCT, patients receive mycophenolate mofetil PO every 8 hours on days 0 to 100 followed by a taper until day 156 in the absence of GVHD.
Interventions
Given IV
Undergo low-dose TBI
Given IV
Given PO or IV
Given PO
Undergo allogeneic stem cell transplantation
Undergo PBSCT
Undergo GVHD prophylaxis/therapy
Eligibility Criteria
You may qualify if:
- The patient must be not eligible for conventional transplants and must have disease expected to be stable for at least 100 days without chemotherapy
- Patients with hematologic malignancies treatable with HCT will be included:
- Aggressive non-Hodgkin lymphomas (NHLs) and other histologies such as diffuse large B-cell NHL: not eligible for autologous HCT, not eligible for conventional myeloablative HCT, or after failed autologous HCT;
- Low grade NHL: with \< 6 month duration of complete response (CR) between courses of conventional therapy;
- Mantle cell NHL: may be treated in first CR;
- Chronic lymphocytic leukemia (CLL): must have failed 2 lines of conventional therapy and must be refractory to fludarabine; this includes patients who fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog\] or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine \[or another nucleoside analog);
- Hodgkin's disease (HD): must have received and failed frontline therapy and have failed or were not eligible for autologous transplant;
- Multiple myeloma (MM): must have received prior chemotherapy or failed autografting; following a planned autologous transplant \[tandem\] is allowed;
- Acute myeloid leukemia (AML): must have \< 5% marrow blasts at the time of transplant;
- Acute lymphocytic leukemia (ALL): must have \< 5% marrow blasts at the time of transplant;
- Chronic myelogenous leukemia (CML): patients will be accepted beyond first clinical progression (CP1) if they have received previous myelosuppressive chemotherapy or HCT, and have \< 5% marrow blasts at time of transplant;
- Myelodysplastic syndrome/myeloproliferative disease (MDS/MPD): must have failed previous myelosuppressive chemotherapy or HCT, and have \< 5% marrow blasts at time of transplant;
- Waldenstrom's macroglobulinemia: must have failed 2 courses of therapy
- Patient with related or unrelated donors for whom:
- There is a likelihood of disease progression while HLA typing and results of a preliminary search and the donor pool suggest that a 10/10 HLA-A, B, C, DRB1 and DQB1 matched unrelated donor will not be found;
- +4 more criteria
You may not qualify if:
- Positive crossmatch between donor and recipients
- Patient's life expectancy is severely limited by diseases other than malignancy
- Patient has central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
- Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML
- Patient is a fertile man or woman unwilling to use contraceptives during and for up to 12 months post treatment
- Patient is a female who is pregnant or breastfeeding
- Patient is human immunodeficiency virus (HIV) positive
- Patients with active non-hematologic malignancies (except non-melanoma skin cancers)
- Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a \> 20% risk of disease recurrence
- Patient has a fungal infection with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
- Patient has the following organ dysfunction:
- Symptomatic coronary artery disease or ejection fraction \< 35% or other cardiac failure requiring therapy; ejection fraction is required if age \> 50 years or if the patient has a history of anthracyclines or history of cardiac disease;
- Diffusion capacity of the lung for carbon monoxide (DLCO) \< 35% total lung capacity (TLC) \< 35%, forced expiratory volume of the lung in one second (FEV1) \< 35% and/or receiving supplementary continuous oxygen; the FHCRC study principal investigator (PI) must approve enrollment of all patients with pulmonary nodules;
- Liver function abnormalities: patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3mg/dL, or symptomatic biliary disease
- Patient has poorly controlled hypertension and on multiple antihypertensives
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (2)
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
University of Torino
Torino, 10126, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Brenda M. Sandmaier
- Organization
- Fred Hutchinson Cancer Research Center
Study Officials
- PRINCIPAL INVESTIGATOR
Brenda Sandmaier
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
July 8, 2005
First Posted
July 11, 2005
Study Start
March 1, 2005
Primary Completion
July 1, 2010
Study Completion
May 26, 2015
Last Updated
May 30, 2017
Results First Posted
May 30, 2017
Record last verified: 2017-04