Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia
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|ClinicalTrials.gov Identifier: NCT00060424|
Recruitment Status : Completed
First Posted : May 7, 2003
Results First Posted : December 8, 2017
Last Update Posted : December 8, 2017
|Condition or disease||Intervention/treatment||Phase|
|B-Cell Prolymphocytic Leukemia Chronic Lymphocytic Leukemia Prolymphocytic Leukemia Recurrent Chronic Lymphocytic Leukemia Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia T-Cell Prolymphocytic Leukemia||Drug: Cyclosporine Drug: Fludarabine Phosphate Procedure: Hematopoietic Cell Transplantation Other: Laboratory Biomarker Analysis Drug: Mycophenolate Mofetil Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation Radiation: Total-Body Irradiation||Phase 2|
I. To determine whether nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from matched-related donors can improve the probability of survival 18 months after treatment for fludarabine (fludarabine phosphate)-refractory, fludarabine phosphate, cyclophosphamide, and rituximab (FCR)-failed, or del 17p chronic lymphocytic leukemia (CLL) beyond that observed in historical controls (30%).
I. To assess the rate of relapse with allogeneic HSCT using nonmyeloablative conditioning for patients with fludarabine-refractory, FCR-failed, or del 17p CLL compared with historical data on autologous HSCT.
II. To estimate the incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD in patients with CLL treated with low-dose TBI, fludarabine, peripheral blood stem cell (PBSC) infusion and immunosuppression with cyclosporine and mycophenolate mofetil.
III. To characterize the rate and types of infections with this regimen.
IV. To estimate the rate of transplant-related mortality in the first 200 days.
NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and TBI on day 0.
TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine orally (PO) every 12 hours on days -3 to 180 with taper beginning on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.
After completion of study treatment, patients are followed up at 12 and 18 months and then annually for 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Allogeneic Hematopoietic Stem Cell Transplantation With Nonmyeloablative Conditioning for Patients With Chronic Lymphocytic Leukemia - A Multi-center Trial|
|Study Start Date :||March 2003|
|Actual Primary Completion Date :||September 2010|
|Actual Study Completion Date :||September 22, 2010|
Experimental: Treatment (enzyme inhibitor, transplant, GVHD prophylaxis)
NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.
Drug: Fludarabine Phosphate
Procedure: Hematopoietic Cell Transplantation
Undergo allogeneic peripheral blood stem cell transplant
Other: Laboratory Biomarker Analysis
Drug: Mycophenolate Mofetil
Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic peripheral blood stem cell transplant
Radiation: Total-Body Irradiation
- Overall Survival [ Time Frame: At 18 months ]Number of patients surviving 18 months post-transplant.
- Rate of Relapse [ Time Frame: 18 months ]Number of patients with relapsed disease post-transplant. Relapse/progression is defined as 1) Physical exam/Imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, 2) circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, or 3) lymph node Biopsy Richter's transformation.
- Acute Grade II-IV GVHD and Chronic (Extensive) GVHD [ Time Frame: aGVHD: 100 days after transplant; cGVHD: 1 Year after transplant. ]
Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages
a maculopapular eruption involving < 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation
bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin > 15 mg/100 mL
Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 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.
aGVHD Grades Grade II: Stage 1 - 3 skin and/or stage 1 gut involvement and/or stage 1 liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
- Rate and Types of Infections [ Time Frame: 18 months ]Number of infections patients experienced, by infection type.
- Transplant-related Mortality [ Time Frame: At 200 days ]Defined as death before day +200 not related to progression of disease.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00060424
|United States, Washington|
|Veterans Administration Center-Seattle|
|Seattle, Washington, United States, 98108|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|University of Torino|
|Torino, Italy, 10126|
|Principal Investigator:||David Maloney||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|