Allogeneic Hematopoietic Cell Transplantation for Patients With Busulfex-based Regimen
LCCC0510
2 other identifiers
interventional
54
1 country
1
Brief Summary
RATIONALE: Giving chemotherapy, such as fludarabine and busulfan, before a donor peripheral stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps 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 a monoclonal antibody, alemtuzumab, before the transplant and tacrolimus after the transplant may stop this from happening. PURPOSE: The phase I portion of this trial identified the maximum tolerated dose of busulfan after treating 40 patients on a dose-escalation scheme. We are now treating an additional 26 patients on the phase II portion of the trial at a Pharmacokinetic (PK)-directed dose of total area under curve (AUC) 6912 micrometer (uM)-min/24 hours. We transitioned to the Phase II portion of the study in October 2009.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Oct 2005
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2005
CompletedFirst Submitted
Initial submission to the registry
March 14, 2007
CompletedFirst Posted
Study publicly available on registry
March 16, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2015
CompletedResults Posted
Study results publicly available
July 17, 2017
CompletedJuly 17, 2017
June 1, 2017
10.1 years
March 14, 2007
April 17, 2017
June 16, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Three-year Relapse-free Survival (RFS) Rate at the Maximum Tolerated Dose Identified During Phase I of the Trial (Target AUC 6912)
Relapse is defined as new or increased sites of disease or positive one marrow after a complete response (CR). The RFS was calculated as the percentage of patients who were alive and without relapse at 3 years
Three years post-transplant
Number of Participants With Dose Limiting Toxicities (DLTs)
Dose limiting toxicity will be defined as any irreversible grade 3 or any grade 4 non-hematologic toxicity that is related to busulfan infusion and not graft vs host disease or late infection after recovery from the initial period of myelosuppression. The maximum tolerated dose (MTD) is defined as the dose with probability of dose limiting toxicity (DLT) of 0.25. The dose of continuous infusion IV busulfan based on blood levels derived from a test dose in conjunction with fludarabine and alemtuzumab plus tacrolimus for GVHD prophylaxis.
first 6 weeks or 42 days following stem cell infusion
Secondary Outcomes (4)
Capacity of Test Dosing of Busulfan That Would Result in the Desired Area Under the Curve Concentration Exposure of Patients Receiving a Full-dose Busulfan Regimen
Day -15 to Day -11
Incidence of Graft vs Host Disease in Patients Between One Month and Two Years Post Transplant
100 days post transplant
Incidence of DNA Chimerism in Patients Between One Month Post Transplant
30 days post transplant
Overall Survival
Three years post-transplant
Study Arms (1)
GVHD prophylaxis
EXPERIMENTALSubjects with matched-related donors (MRDs) were treated with tacrolimus and methotrexate with or without alemtuzumab for graft vs host disease prophylaxis Subjects also receive busulfan and fludarabine . Matched unrelated donor (MUD) or mismatched related donor (MMRD) subjects receive GVHD prophylaxis with rabbit anti-thymocyte globulin (ATG) + Methotrexate Subjects also receive busulfan, fludarabine, and tacrolimus.
Interventions
.5 mg/kg on day -3 and 2.5 mg/kg on day -2
minimum total cluster of differentiation (CD34+) cells of 3 x 10\^6 cells/kg and a maximum of 8 x 10\^6 cells/kg will be infused on day 0
30 mg/m\^2/day x 5 days intravenous piggyback (IVPB) over 30 minutes on Days -7 through -3
A minimum total CD34+ cell dose of 3 x 10\^6 cells/kg and maximum of 8 x 10\^6 cells/kg will be infused on day 0
minimum total CD34+ cell dose of 3 x 10\^6 cells/kg and a maximum of 8 x 10\^6 cells/kg will be infused on day 0
Eligibility Criteria
You may qualify if:
- Histologically confirmed diagnosis of any of the following:
- Chronic lymphocytic leukemia or prolymphocytic leukemia Chemotherapy-refractory or advanced disease after ≥ 3 prior treatments Chronic myelogenous leukemia Diagnosis based on t(9;22) or related t(9;12) cytogenetic abnormalities AND characterized by elevated white blood counts (WBC) in peripheral blood or marrow Patients with progressive disease on imatinib mesylate or other protein tyrosine kinase inhibitors; less than a major cytogenetic or fluorescent in situ hybridization (FISH) complete response (CR) after a minimum of 6 months of targeted therapy; or less than a complete FISH or cytogenetic response after 12 months of targeted therapy are eligible Patients with other cytogenetic abnormalities, such as t(9;12), that are associated with an aggressive clinical course are eligible Non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma Any World Health Organization (WHO) classification histologic subtype allowed Must have advanced disease as defined by relapse after initial CR or failure to achieve CR OR deemed to have less than a 30% likelihood of durable response with an autologous stem cell transplant Refractory low-grade NHL histologies or any intermediate or aggressive large cell or mantle cell lymphoma allowed Acute myeloid leukemia (AML) High-risk disease in first CR (CR1) OR evidence of any recurrent disease beyond CR1 High-risk individuals are those requiring more than 1 course of induction therapy to achieve remission; those with extra-medullary disease at presentation; or those with high-risk cytogenetic abnormalities (abnormalities of chromosomes 5, 7, 2, trisomy 8, or 3) or \> 2 cytogenetic abnormalities
- Multiple myeloma
- Myelodysplastic syndromes (MDS) Must have MDS defined by WHO criteria with \> 5% blasts or high-risk cytogenetic abnormalities (abnormalities of chromosomes 5, 7, 2, trisomy 8, or 3)
- Acute lymphoblastic leukemia (ALL) High-risk disease in CR1 OR beyond CR1 High-risk disease includes the following: t(9;22) or t(4;11); WBC \> 30,000/mm³ at presentation; non-T-cell phenotype; or more than 30 years of age
- Myelofibrosis/agnogenic myeloid metaplasia
- Patients must be transfusion dependant or have evidence of evolving AML as evidenced by an excess of blasts or a state of marrow failure/fibrosis
- Myeloproliferative disorders with advanced disease (e.g., progressive or spent phase polycythemia vera, myelofibrosis, or essential thrombocythemia)
- Any of the following categories of donors are acceptable\*:
- Human Leucocyte Antigen (HLA)-identical or 1 antigen-mismatched sibling (5/6, 6/6, or 8/10) donor
- Minimal serologic typing required for class I (A, B); molecular typing required for class II (DRB1)
- /10 matched unrelated donor (MUD)
- Molecular analysis at HLA-A, -B, -C, -DRB1 and -DQB1 (8/10 match) by high resolution typing is required
- /6 MUD
- Molecular analysis at HLA-A, -B, and -DRB1 required Note: \*No syngeneic donors
- +10 more criteria
You may not qualify if:
- PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 4 weeks since prior chemotherapy, radiotherapy, or surgery
- Cranial radiotherapy or intrathecal therapy as prophylaxis against central nervous system (CNS) recurrence within the past 4 weeks allowed (in high-risk patients)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- UNC Lineberger Comprehensive Cancer Centerlead
- National Cancer Institute (NCI)collaborator
- Otsuka America Pharmaceuticalcollaborator
Study Sites (1)
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599-7295, United States
Related Publications (1)
Shea TC, Walko C, Chung Y, Ivanova A, Sheets J, Rao K, Gabriel D, Comeau T, Wood W, Coghill J, Armistead P, Sarantopoulos S, Serody J. Phase I/II Trial of Dose-Escalated Busulfan Delivered by Prolonged Continuous Infusion in Allogeneic Transplant Patients. Biol Blood Marrow Transplant. 2015 Dec;21(12):2129-2135. doi: 10.1016/j.bbmt.2015.07.016. Epub 2015 Jul 22.
PMID: 26210442RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Thomas Shea
- Organization
- UNC Lineberger Comprehensive Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Thomas C. Shea, MD
UNC Lineberger Comprehensive Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 14, 2007
First Posted
March 16, 2007
Study Start
October 1, 2005
Primary Completion
November 1, 2015
Study Completion
November 1, 2015
Last Updated
July 17, 2017
Results First Posted
July 17, 2017
Record last verified: 2017-06
Data Sharing
- IPD Sharing
- Will not share