Donor Stem Cell Transplant in Treating Patients With High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Condition: Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: rituximab; busulfan; cyclophosphamide; fludarabine phosphate; methotrexate; sirolimus; tacrolimus; allogeneic stem cell transplant
Intervention MeSH terms: Sirolimus; Cyclophosphamide; Busulfan; Rituximab; Methotrexate; Fludarabine; Fludarabine phosphate; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 68.0
Sex: All
Minimum age: 18 Years
Maximum age: 69 Years
Healthy volunteers: No
Keywords: refractory chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; B-cell chronic lymphocytic leukemia; contiguous stage II small lymphocytic lymphoma; noncontiguous stage II small lymphocytic lymphoma; recurrent small lymphocytic lymphoma; stage I small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma

Summary:

      RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop
      the growth of cancer cells. It may also stop the patient's immune system from rejecting the
      donor's stem cells. Also, monoclonal antibodies, such as rituximab, can find cancer cells and
      either kill them or deliver cancer-killing substances to them without harming normal cells.
      The donated stem cells may replace the patient's immune cells and help destroy any remaining
      cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can
      also make an immune response against the body's normal cells. Giving tacrolimus, sirolimus,
      and methotrexate after the transplant may stop this from happening.

      PURPOSE: This phase II trial is studying how well donor stem cell transplant works in
      treating patients with high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma.
    

Eligibility criteria:

        Patient Eligibility:

          1. Diagnosis of B-cell chronic lymphocytic leukemia or B-cell small lymphocytic lymphoma.

             Diagnosis should be according to International Workshop on Chronic Lymphocytic
             Leukemia (IWCLL) 2008 Criteria

               1. Early Disease Cohort - Patients in the early disease cohort must include one or
                  more of the following:

                    -  FISH showing deletion 17p in ≥ 20% of cells (either at diagnosis or any time
                       prior to study entry) either alone or in combination with other cytogenetic
                       abnormalities

                    -  FISH showing del 11q in ≥ 20% of cells (either at diagnosis or any time
                       prior to study entry) either alone or in combination with other cytogenetic
                       abnormalities, unless the patient has achieved a complete remission by IWCLL
                       2008 which includes CT scan, bone marrow morphology and flow cytometry

                    -  Failure to achieve a partial response with initial chemotherapy, but with
                       lack of progression. These patients may receive a second therapy to improve
                       their response prior to transplant.

                    -  Patients who, at the time of first progression, have a 17p deletion by FISH
                       in ≥ 20% of cells, either alone or in combination with other cytogenetic
                       abnormalities.

                  The duration of the first progression is not specified.

                    -  In addition, patients in the early disease cohort must have all of the
                       following:

                         -  Received at least 2 cycles of induction therapy. It is expected that
                            most patients will receive at least 4 months of therapy prior to
                            enrollment, but this is not required. Suggested regimens include but
                            are not limited to the following: fludarabine plus rituximab,
                            fludarabine, cyclophosphamide plus rituximab, pentostatin,
                            cyclophosphamide plus rituximab, bendumustine plus rituximab, or
                            alemtuzumab alone or in combination with other agents. Patients may
                            receive no more than 2 different regimens prior to proceeding to
                            transplantation.

                         -  Nodes ≤ 5 cm

               2. Advanced Disease Cohort - Patients in the advanced disease cohort must include
                  one or more of the following:

                    -  FISH showing deletion 17p in ≥ 20% of cells (regardless of interval from
                       initial therapy) either alone or in combination with other cytogenetic
                       abnormalities

                    -  First progression < 24 months after completing therapy. This includes
                       progression on initial therapy.

                    -  Second or subsequent progression

                    -  In addition, patients in the advanced disease cohort must have all of the
                       following:

                         -  Stable disease or better by the Revised IWCLL 2008 NCI Criteria to
                            their most recent chemotherapy

                         -  Nodes ≤ 5 cm

          2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

          3. Age Requirement - Patients must be between ≥ 18 and < 70 years of age

          4. Cytotoxic Chemotherapy or Alemtuzamab - There must be at least 4 weeks after day 1 of
             the last cycle of cytotoxic chemotherapy, or alemtuzamab.

          5. Human Immunodeficiency Virus (HIV) Status - Patients must have no HIV infection.

             Allogeneic transplantation in the HIV patient population is not well-defined and there
             are likely to be requirements for concomitant anti-HIV therapy and anti-GVHD therapy
             that would create potentially dangerous pharmacokinetic interactions among the
             different agents that could constrain therapeutic options for controlling both HIV and
             GVHD.

          6. Hepatitis B and C - Patients must have no Hepatitis B sAg, anti-HBc or HCV.

          7. Diffusion capacity of carbon monoxide DLCO must be ≥ 40% predicted

          8. Left ventricular ejection fraction (LVEF) by Echocardiogram (ECHO) or Multiple gated
             acquisition (MUGA) must be ≥ 30%

          9. Diabetes or Serious Infection - Patients must have no uncontrolled diabetes mellitus
             or active uncontrolled serious infections

         10. Pregnancy and Nursing Status - Patients must be non-pregnant and non-nursing.
             Treatment under this protocol would expose a fetus to significant risks. Women of
             childbearing potential should have a negative pregnancy test prior to study entry.

             Women and men of reproductive potential should agree to use an appropriate method of
             birth control throughout their participation in this study due to the teratogenic
             potential of the therapy utilized in this trial. Appropriate methods of birth control
             include oral contraceptives, implantable hormonal contraceptives (Norplant®), or
             double barrier method (diaphragm plus condom).

         11. Richter's Transformation - Patients must have no history of Richter's transformation.

         12. Initial Required Laboratory Values:

               -  Serum Creatinine < 2 mg/dL

               -  Calculated Creatinine Clearance ≥ 40 mL/min

               -  AST < 3 x ULN

               -  Total Bilirubin < 2 mg/dL (except for Gilbert's syndrome)

        Donor Eligibility:

          1. Donors may be either a 6/6 HLA-matched related donor by low-resolution typing at HLA
             A, B, DR.

          2. Donors may be an 8/8 HLA-matched unrelated donor at HLA A, B, C, DR. Unrelated donors
             will be analyzed by molecular typing at both HLA Class I and Class II (A, B, C, DR
             loci).

          3. Syngeneic donors are not eligible

          4. Donors must be healthy and must be an acceptable donor as per institutional standards
             for stem cell donation.

          5. There will be no donor age restriction.