Natural Killer (NK) Cell Adback After Allogeneic Stem Cell Transplant With Campath-IH Plus Chemorx for Patients With Lymphoid Malignancies
Condition: Lymphoma; Leukemia
MeSH terms: Lymphoma; Neoplasms
Intervention: ARA-C; BCNU; Campath-1H; Cyclophosphamide; Etoposide; Fludarabine; Melphalan; Rituximab; Allogeneic Stem Cell Transplantation; Total body radiation (TBI); Methotrexate; Tacrolimus; Adback NK or T Cell
Intervention description: 100 mg/m^2 IV Daily Over 1 Hour for 4 Days; 300 mg/m^2 IV Over 1 Hour for 1 Day; 15 mg IV Daily Over 30 Minutes for 3 Days; 1000 mg/m^2 IV Daily Over 1 Hour for 3 Days; 100 mg/m^2 IV Daily Over 3 Hours for 4 Days; 30 mg/m^2 IV Daily Over 1 Hour for 3 Days; 100 mg/m^2 IV Over 30 Minutes for 1 Day.; 375 mg/m^2 IV Over 5-7 Hours for 1 Day, followed by 1000 mg/m^2 IV Over 5-7 Hours Weekly for 3 Weeks.; Stem Cell Infusion on Day 0.; TBI on Day 5 following chemotherapy, before stem cell infusion.; 5 mg/m2 IV on Days +1, +3, and +6.; 0.03 mg/kg/day IV starting on Day -2, to be given through day 60, tapered by 20% every week, then discontinue by day 90.; Adback natural killer (NK) cells or T cells after transplantation to enhance full engraftment of donor cells. Cell adback after transplantation applies only if there is no active GVHD, and no previous episode of grade II-IV GVHD.
Intervention MeSH terms: Cytarabine; Cyclophosphamide; Melphalan; Carmustine; Rituximab; Methotrexate; Fludarabine; Fludarabine phosphate; Etoposide; Alemtuzumab; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Lymphoma; Leukemia; B-Cell Lymphoid Malignancies; CLL; Cll/Small Lymphocytic Lymphoma; Follicular Lymphoma; Mantle Cell Lymphoma; Diffuse Large Cell Lymphoma; Splenic Lymphoma; MALT; Lymphoplasmacytic Lymphoma; Burkitt's Lymphoma; ARA-C; BCNU; Campath-1H; Cytoxan; Etoposide; Fludarabine; Melphalan; Rituximab; Allogeneic Stem Cell Transplant; T-Cell Cell Adback; Natural Killer (NK) Cell Adback

Summary:

      Primary objective:

        -  To determine the safety of adback T- or Natural Killer (NK) cells in patients with
           lymphoid malignancies receiving allogeneic stem cell transplantation with Campath-IH
           containing conditioning regimen.

      Secondary objective:

        -  To determine the efficacy (disease-free-survival) of this strategy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Up to 70 years of age.

          2. B-cell lymphoid malignancies (those with CD20 negative disease at their diagnosis will
             not receive rituximab): This includes CLL/small lymphocytic lymphoma, follicular
             lymphoma, mantle cell, diffuse large cell, Splenic lymphoma, Mucosa-Associated
             Lymphoid Tissue (MALT), lymphoplasmacytic lymphoma and Burkitt's lymphoma.

          3. Patients in relapse or considered at high risk for relapse.

          4. In order to increase the chance of KIR-mismatching between recipient and donor, a 9/10
             matched (mismatched locus C ) unrelated donor would be preferable. If a mismatched
             donor is not available, then a fully-matched unrelated donor or other 9/10 matched
             unrelated donor will be considered.

          5. A sibling donor who is 9/10 matched may also be allowed.

          6. Zubrod PS </= 2.

          7. Left ventricular ejection fraction (LVEF)>/= 40% with no uncontrolled arrythmias or
             symptomatic heart disease.

          8. Forced expiratory volume in one second (FEV1), Forced Expiratory Volume (FVC) and
             Carbon Monoxide Diffusing Capacity (DLCO) >/= 50%.

          9. Serum creatinine < 1.8 mg/dL. Serum bilirubin < 3 * upper limit of normal,

         10. Aspartate aminotransferase (AST) < 3 * upper limit of normal.

         11. Signed, written Internal Review Board (IRB)-approved informed consent.

         12. Men and women of reproductive potential must agree to follow accepted birth control
             methods for the duration of the study. Female subject is either post-menopausal or
             surgically sterilized or willing to use an acceptable method of birth control (i.e., a
             hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with
             spermicide, or abstinence) for the duration of the study. Male subject agrees to use
             an acceptable method for contraception for the duration of the study.

        Exclusion Criteria:

          1. Past history of anaphylaxis following exposure to CAMPATH-IH or Rituximab

          2. Patient with active Central Nervous System (CNS) disease.

          3. Positive Beta human chorionic gonadotrophin (hCG) text in a woman with child bearing
             potential defined as not post-menopausal for 12 months or no previous surgical
             sterilization, or currently breast-feeding.

          4. Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.

          5. Patients with other malignancies diagnosed within 2 years prior to Study registration
             (except skin squamous cell carcinoma).

          6. Active uncontrolled bacterial, viral or fungal infections.

          7. Major surgical procedure or significant traumatic injury within 4 weeks prior to Study
             registration.

          8. Serious, non-healing wound, ulcer, or bone fracture.

          9. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to Study registration.

         10. History of Stroke within 6 months.

         11. Myocardial infarction within the past 6 months prior to Study registration.

         12. Uncontrolled chronic diarrhea.

         13. A prior allogeneic transplant from the same donor. Is there an age limit? Yes