Chronic Lymphocytic Leukemia

 Phase II Study of Reduced-Intensity Allogeneic Stem Cell Transplant for High-Risk Chronic Lymphocytic Leukemia (CLL)

 Cancer and Leukemia Group B (CALGB)

 CALGB 100701; NCT01027000

 Member institutions of CALGB and the Blood and Bone Marrow Transplant Clinical Trials Network

 CALGB 100701 is a multicenter phase II study of reduced intensity HLA matched-related and matched-unrelated allogeneic stem cell transplantation in two distinct cohorts of patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). While CALGB is the lead coordinating group (Study Chair, Dr. Edwin Alyea), the CLL Research Consortium is directing the immunologic correlative science (Correlative Science Co-Chair, Dr. John Gribben), and the Blood and Bone Marrow Transplant Clinical Trial Network has also agreed to participate. The first cohort (Cohort 1) consists of patients with high-risk disease who have received a single therapy. Risk stratification is based on genetic characterization and response to treatment, and high-risk patients include those with del(17p13.1) in complete or partial remission, del(11q22.3) in partial remission, or any other patient who does not attain a partial or better response to any chemoimmunotherapy-based treatment. These patients can be treated with another cytoreductive treatment to prepare them for transplant, but they can receive no more than two treatments prior to transplant. Cohort 2 consists of patients with a brief first remission (< 24 months) following therapy and those who have relapsed following two or more prior therapies. Each cohort will be treated with one of two standard immune suppressive and cytoreductive regimens (rituximab, busulfan, and fludarabine or rituximab, fludarabine, and cyclophosphamide) commonly used for reduced-intensity allogeneic stem cell transplantation with defined graft-versus-host disease (GVHD) prophylaxis along with rituximab maintenance to further reduce development and severity of GVHD. The primary endpoint of this study is to determine if two-year progression-free survival (PFS) of Cohort 1 is improved over that observed in historical controls receiving only chemoimmunotherapy. A variety of secondary endpoints will also be addressed that are of interest to the field of CLL and transplant, including determination of whether two-year PFS of ≥ 50 percent can be achieved and two-year PFS of ≤ 30 percent can be excluded in patients with CLL and SLL in the advanced disease cohort (Cohort 2).

 Available chemoimmunotherapy options for high-risk CLL are unsatisfactory, with many patients dying in the first two years post-treatment. Application of transplantation after first relapse is suboptimal because candidates often have significant residual disease as a consequence of incomplete cytoreduction due to drug-resistant tumor. This trial addresses a sentinel question: Can allogeneic immune therapy ameliorate the adverse outcome observed in patients with high-risk genetic abnormalities and in those with primary refractory disease? Participation in this clinical trial will necessitate referral to a CLL transplant team by treating physicians at a time either prior to or early in first treatment of high-risk CLL patients.

 This trial brings together three separate groups (through the hard work of Dr. Charles Linker) supported by the NCI and NHLBI, with expertise in CLL and transplantation (CALGB), CLL transplant immunology (CLL Research Consortium), and transplantation (Blood and Bone Marrow Transplant Clinical Trial Network). It is strongly endorsed by each of the groups and represents an outstanding option for eligible patients who have either a related or an unrelated HLA matched donor.