Lymphoma Clinical Trial
— LCCC 0510Official title:
Allogeneic Hematopoietic Cell Transplantation for Patients With Hematologic Disorders Who Are Undergoing Dose-Adjusted Treatment With A Maximally Intensive Busulfex-Based Therapeutic Regimen
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 PK-directed dose of total AUC 6912
uM-min/24 hours. We transitioned to the Phase II portion of the study in October 2009.
Status | Active, not recruiting |
Enrollment | 60 |
Est. completion date | August 2017 |
Est. primary completion date | November 2016 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 55 Years |
Eligibility |
DISEASE CHARACTERISTICS: - 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 WBC counts 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 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*: - 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) - 8/10 matched unrelated donor (MUD) - Molecular analysis at HLA-A, -B, -C, -DRB1 and -DQB1 (8/10 match) by high resolution typing is required - 5/6 MUD - Molecular analysis at HLA-A, -B, and -DRB1 required NOTE: *No syngeneic donors PATIENT CHARACTERISTICS: - Performance status 0-2 - Bilirubin = 2 times upper limit of normal (ULN) - AST = 2 times ULN - Creatinine clearance = 50 mL/min - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - DLCO > 60% with no symptomatic pulmonary disease - LVEF = 50% by MUGA - No uncontrolled or severe cardiovascular disease, pulmonary disease, or infection that, in the opinion of the treating physician, would make this study unreasonably hazardous to the patient - No other serious illness that would limit survival to < 2 years - No psychiatric condition that would preclude study compliance - No uncontrolled diabetes mellitus or active serious infection - No active second malignancy except for nonmelanomatous skin cancer - No known hypersensitivity to E. coli-derived products - No HIV positivity PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 4 weeks since prior chemotherapy, radiotherapy, or surgery - Cranial radiotherapy or intrathecal therapy as prophylaxis against CNS recurrence within the past 4 weeks allowed (in high-risk patients) |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill | North Carolina |
Lead Sponsor | Collaborator |
---|---|
UNC Lineberger Comprehensive Cancer Center | National Cancer Institute (NCI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | One-year disease-free survival (DFS) rate at the maximum tolerated dose identified during phase I of the trial (target AUC 6912) | One year post-transplant | No | |
Secondary | Overall and disease-free survival | Five years post-transplant | No | |
Secondary | Dose-limiting toxicities of busulfan | 6 weeks post-transplant | Yes | |
Secondary | 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 | No | |
Secondary | To assess the incidence of graft vs host disease and DNA chimerism in patients between one month and two years post transplant | 1 Month to 2 Years post-transplant | No |
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