Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders
|ClinicalTrials.gov Identifier: NCT00301834|
Recruitment Status : Completed
First Posted : March 13, 2006
Results First Posted : May 16, 2013
Last Update Posted : September 28, 2017
RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as fludarabine and busulfan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell, bone marrow , or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine together with methotrexate and methylprednisolone may stop this from happening.
PURPOSE: This phase II trial is studying how well giving alemtuzumab together with fludarabine and busulfan works when given before donor stem cell transplant in treating young patients with hematologic disorders.
|Condition or disease||Intervention/treatment||Phase|
|Congenital Amegakaryocytic Thrombocytopenia Diamond-blackfan Anemia Leukemia Myelodysplastic Syndromes Severe Congenital Neutropenia||Biological: alemtuzumab Drug: busulfan Drug: cyclosporine Drug: fludarabine phosphate Drug: methotrexate Drug: methylprednisolone Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Procedure: umbilical cord blood transplantation||Phase 2|
- Determine the engraftment rate with reduced toxicity ablative conditioning regimen comprising alemtuzumab, fludarabine, and busulfan followed by allogeneic stem cell transplantation in pediatric patients with stem cell defects, marrow failure syndromes, hemoglobinopathy, severe immunodeficiency syndromes (nonsevere combined immunodeficiency disorders), myelodysplastic syndromes, or myeloid leukemia.
- Determine the acute reactions, incidence of infections, and rate of immune reconstitution in patients treated with this regimen.
OUTLINE: This is a multicenter study.
- Conditioning regimen: Patients receive alemtuzumab IV over 6 hours on days -12 to -10, high-dose busulfan IV over 2 hours 4 times daily on days -9 to -6, and fludarabine IV over 30 minutes on days -5 to -2.
- Allogeneic stem cell transplantation: Two days after the completion of conditioning regimen, patients undergo allogeneic bone marrow, peripheral blood stem cell, or umbilical cord blood transplantation on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 5 and continuing until blood counts recover.
Graft-vs-host disease (GVHD) prophylaxis:
- Most transplantations (bone marrow or peripheral blood stem cell transplantation): Patients receive cyclosporine IV continuously beginning on day -1 until at least day 50 followed by a taper at either 2 months, 9 months, or 1 year in the absence of GVHD. Patients also receive methotrexate on days 1, 3, and 6.
- Umbilical cord blood transplantation: Patients receive cyclosporine as in most transplantations, and methylprednisolone IV twice daily on days 0-21 followed by a weekly taper.
After transplantation, patients are followed periodically for up to 20 years.
PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Evaluation of Fludarabine, Busulfan and Alemtuzumab as a Reduced Toxicity Ablative Bone Marrow Stem Cell Transplant Regimen for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myelodysplastic Syndrome (MDS)/Leukemia|
|Study Start Date :||January 2005|
|Primary Completion Date :||September 2011|
|Study Completion Date :||September 2011|
Experimental: Single arm - conditioning and transplant
Alemtuzumab 0.5 mg/kg (maximum 15 mg) daily for 3 days; Busulfan i.v. every 6 hours from day -9 to day -6 for 16 total doses; Fludarabine phosphate from day -5 for 4 days at 1.3 mg/kg (if patient was less than 12 kg) or 40 mg/m*2 per dose; Cyclosporine continuous infusion 3 mg/kg/Day beginning day -1 for GVHD prophylaxis; Methotrexate at 15 mg/m*2 on day +1, 10 mg/m*2 on days +3, +6, and (only for MUDs) day +11 also for GVHD prophylaxis; Methylprednisolone only as required for GVHD prophylaxis; allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation or peripheral blood stem cell transplantation or umbilical cord blood transplantation.
|Biological: alemtuzumab Drug: busulfan Drug: cyclosporine Drug: fludarabine phosphate Drug: methotrexate Drug: methylprednisolone Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Procedure: umbilical cord blood transplantation|
- Number of Participants Achieving Durable Engraftment (Presence of Donor Cells) at 6 Weeks Post Transplantation [ Time Frame: 6 weeks post-transplant ]Peripheral blood chimerism studies were performed by quantitative real time polymerase chain reaction (qPCR) evaluation of differential short tandem repeat DNA sequences
- Treatment-related Mortality at 100 Days and 1 Year Post Transplantation [ Time Frame: 100 days and 1 year ]
- Toxicity Grade ≥ 3 From Start of Conditioning Through the First Year Post Transplantation [ Time Frame: 1 year post-transplantation ]
- Cytomegalovirus (CMV) Viral Infection and Disease Symptoms [ Time Frame: Up to one year post-transplant ]polymerase chain reaction testing for presence of CMV weekly until at least day +100 then every 2 weeks until T-cell reconstitution as defined by cluster of differentiation 4 (CD4) > 200 cells/mm3. Median time to T-cell reconstitution was 6 months.
- Disease-free Survival With Correction of Disease at One Year Post Transplantation [ Time Frame: 1 year post-transplantation ]Patients deemed "alive and well" at follow-up timepoint later than 1-year post-transplantation
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00301834
|United States, California|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94115|
|United States, Wisconsin|
|University of Wisconsin Paul P. Carbone Comprehensive Cancer Center|
|Madison, Wisconsin, United States, 53792-6164|
|Study Chair:||Morton J. Cowan, MD||University of California, San Francisco|