Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
|ClinicalTrials.gov Identifier: NCT01529827|
Recruitment Status : Active, not recruiting
First Posted : February 9, 2012
Results First Posted : July 2, 2017
Last Update Posted : September 12, 2017
|Condition or disease||Intervention/treatment||Phase|
|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) Adult Grade III Lymphomatoid Granulomatosis Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Aplastic Anemia Burkitt Lymphoma Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Childhood Chronic Myelogenous Leukemia Childhood Diffuse Large Cell Lymphoma Childhood Grade III Lymphomatoid Granulomatosis Childhood Immunoblastic Large Cell Lymphoma Childhood Myelodysplastic Syndromes Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Myelomonocytic Leukemia Chronic Phase Chronic Myelogenous Leukemia Congenital Amegakaryocytic Thrombocytopenia Diamond-Blackfan Anemia Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hepatosplenic T-cell Lymphoma Juvenile Myelomonocytic Leukemia Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Nodal Marginal Zone B-cell Lymphoma Paroxysmal Nocturnal Hemoglobinuria Peripheral T-cell Lymphoma Polycythemia Vera Post-transplant Lymphoproliferative Disorder Previously Treated Myelodysplastic Syndromes Primary Myelofibrosis Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Childhood Grade III Lymphomatoid Granulomatosis Recurrent Childhood Large Cell Lymphoma Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Small Noncleaved Cell Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell 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 Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Secondary Myelofibrosis Severe Combined Immunodeficiency Severe Congenital Neutropenia Shwachman-Diamond Syndrome Splenic Marginal Zone Lymphoma T-cell Large Granular Lymphocyte Leukemia Waldenstrom Macroglobulinemia Wiskott-Aldrich Syndrome||Drug: fludarabine phosphate Drug: melphalan Radiation: total-body irradiation Drug: tacrolimus Drug: mycophenolate mofetil Drug: methotrexate Other: laboratory biomarker analysis Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation||Phase 2|
I. To determine the transplant related mortality (TRM) of this reduced-intensity transplantation (RIT) combination, fludarabine (fludarabine phosphate), melphalan, and TBI in a patient population usually not eligible for a full a myeloablative allogeneic hematopoietic stem cell transplantation (HSCT).
I. To evaluate clinical response, progression free survival (PFS) at one year, engraftment rate, and graft-versus-host disease (GvHD) incidence with the proposed RIT regimen across a variety of hematological conditions.
II. Correlative studies will include chimerism analysis by molecular analysis and evaluation of immune reconstitution by cytomegalovirus (CMV) dextramer analysis using flow cytometry.
OUTLINE: PREPARATIVE REGIMEN:
Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -5 to -2 and melphalan IV over 30 minutes on day -2. Patients undergo low-dose TBI twice daily (BID) on day -1.
Patients undergo allogeneic PBSCT on day 0.
Patients receive tacrolimus IV or orally (PO) BID on days -1 to 100 with taper over 4-6 months, MMF PO or IV every 6-8 hours on days -1 to 60, and methotrexate IV over 15-30 minutes on days 1, 3, and 6. After completion of study treatment, patients are followed up periodically.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||94 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Reduced Intensity Allogeneic Stem Cell Transplantation With Fludarabine, Melphalan and Low Dose Total Body Irradiation|
|Actual Study Start Date :||February 28, 2012|
|Primary Completion Date :||May 28, 2015|
|Estimated Study Completion Date :||May 1, 2018|
Experimental: Treatment (reduced intensity allogeneic PBSCT)
PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan IV over 30 minutes on day -2. Patients undergo low-dose TBI BID on day -1. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. GvHD PROPHYLAXIS: Patients receive tacrolimus IV or PO BID on days -1 to 100 with taper over 4-6 months, MMF PO or IV every 6-8 hours on days -1 to 60, and methotrexate IV over 15 to 30 minutes on days 1, 3, and 6.
Drug: fludarabine phosphate
Other Names:Drug: melphalan
Other Names:Radiation: total-body irradiation
Other Name: TBIDrug: tacrolimus
Given IV or PO
Other Names:Drug: mycophenolate mofetil
Given IV or PO
Other Names:Drug: methotrexate
Other Names:Other: laboratory biomarker analysis
Correlative studiesProcedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSCTProcedure: peripheral blood stem cell transplantation
- Transplant Related Mortality (TRM) [ Time Frame: In the first 100 days from day 0 of transplant ]Day 100 transplant related mortality (TRM). An exact 95% confidence interval will be provided.
- Clinical Response [ Time Frame: In the first 100 days from day 0 of transplant ]
Patients will be followed according to response criteria as referenced in BMT SOP "Standards of Therapy" last updated 2008. Clinical Response = CR + PR.
Complete Response Requires all of the following:
- Serum and urine negative for monoclonal proteins by immunofixation
- Normal free light chain ratio
- Plasma cells in marrow < 5%
Partial Response (PR) Requires any of the following:
- ≥ 50% reduction in current serum monoclonal protein levels > 0.5 g/dL or urine light chain levels > 100 mg/day with a visible peak or free light chain levels > 10mg/dL
Progressive Disease (PD) Requires any of the following:
- If progressing from CR, any detectable monoclonal protein or abnormal free light chain ratio (light chain must double)
- If progressive from PR or SD, ≥ 50% increase in the serum M protein to > 0.5 g/dL,or ≥ 50% increase in urine M protein to > 200mg/day with visible peak present.
- Free light chain increase of ≥ 50% to
- Progression Free Survival (PFS) at One Year [ Time Frame: day of transplant until progression up to 5 years ]Assessed using Kaplan Meier and Proportional Hazards
- Median Time to Neutrophil Engraftment [ Time Frame: Day 100 ]Median time to recovery of absolute neutrophil count >=500/uL for 3 consecutive days. Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01529827
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||George Chen||Roswell Park Cancer Institute|