Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD
Condition: Leukemia, Mast-Cell; Mantle-cell Lymphoma
MeSH terms: Lymphoma, Mantle-Cell; Leukemia, Mast-Cell
Intervention: Total lymphoid irradiation; Rituximab; Anti-thymoglobulin, rabbit (ATG, rabbit ATG); Cyclosporine; Mycophenylate mofetil; Filgrastim; Granisetron; Solumedrol; Acetaminophen; Diphenhydramine; Hydrocortisone
Intervention description: Total lymphoid irradiation (TLI) administered at 80cGy for 10 days; Rituximab 375 mg/m2 administered as an intravenous (IV) infusion once weekly for 4 doses.; Rabbit anti-thymoglobulin (ATG) administered from Day -11 through Day -7 (5 doses) at 1.5 mg/kg/day, for a total dose of 7.5 mg/kg.; Cyclosporine (CSP) administered orally at 6.25 mg/kg twice-a-day (BID) from Day -3 until through Day +56 post-peripheral blood progenitor cell (PBPC) infusion. Dose may be adjusted to maintain a therapeutic level of cyclosporine, or in response to renal insufficiency. If at Day +56, chimerism assessment demonstrates > 40% donor cells in the CD3+ lineage, and the patient is without evidence of GvHD, then cyclosporine taper will begin (6% reduction per week).; Mycophenylate mofetil (MMF) will be administered at 15 mg/kg po Day 0, at 5 to 10 hours after mobilized PBPC infusion is complete; Filgrastim provided as needed for neutrophil support; Granisetron administered as an anti-nausea agent (anti-emetic) at 1 mg orally 30 to 60 minutes before TLI; Solumedrol, an anti-inflammatory glucocorticoid containing methylprednisolone sodium succinate, administered at 1 mg/kg as a premedication for anti-thymoglobulin (ATG); Acetaminophen administered orally at 650 mg 1 hour prior to infusion of PBPC; Diphenhydramine administered by intravenous infusion at 50 mg 1 hour prior to infusion of PBPC; Hydrocortisone administered by intravenous infusion at 100 mg 1 hour prior to infusion of PBPC
Intervention MeSH terms: Acetaminophen; Diphenhydramine; Promethazine; Cyclosporine; Hydrocortisone; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Rituximab; Granisetron; Lenograstim; Cyclosporins; Thymoglobulin; Antilymphocyte Serum; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 76 Years
Healthy volunteers: No

Summary:

      To determine if rituximab administered after allogeneic transplantation decreases the
      incidence of chronic graft-vs-host disease (cGvHD)
    

Eligibility criteria:

        Recipient Inclusion Criteria:

          -  Between 18 and 76 years of age

          -  Chronic lymphocytic leukemia (CLL):

               -  Unmutated IgG VH gene status

               -  Mutated IgG VH genes (> 2% nucleotide change compared to somatic sequence)

               -  Complete remission benefit most from allogeneic hematopoietic stem cell
                  transplant (HSCT).

        (Physicians will be encouraged to provide aggressive chemotherapy prior to nonmyeloablative
        transplantation.)

          -  Mantle cell lymphoma (MCL): Transplant physicians believe subject would benefit from
             allogeneic HSCT.

          -  Adequate renal (Cr < 2.4 mg/dL) and hepatic (Bilirubin < 3.0 mg/dL, Aspartate
             aminotransferase (AST) < 100 IU) function.

          -  Men and women of reproductive potential must agree to use an acceptable method of
             birth control during treatment and for six months after completion of treatment.

          -  All subjects must provide written informed consent

        Donor Inclusion Criteria:

          -  Genotypically or phenotypically human leukocyte antigen (HLA)-identical.

          -  Age < 76 unless cleared by institutional PI

          -  Capable of giving written, informed consent.

          -  Must consent to peripheral blood stem cell (PBSC) mobilization with G-CSF and
             apheresis

        Recipient Exclusion Criteria:

          -  Recipient has a 9 of 10 or 10 of 10 HLA identical donor (high resolution molecular
             genotyping at HLA A, B, C and DrB1, and DQ)

          -  Pregnancy

          -  Lactating

          -  Serious uncontrolled infection

          -  HIV seropositivity

          -  Hepatitis B or C seropositivity

          -  Cardiac function: ejection fraction < 40% or uncontrolled cardiac failure

          -  Pulmonary: Diffusing capacity - carbon monoxide (DLCO) < 50% predicted

          -  Liver function abnormalities: elevation of bilirubin to ≥ 3 mg/dL and/or AST > 100

          -  Renal: creatinine > 2.4

          -  Karnofsky performance score ≤ 60%

          -  Patients with poorly controlled hypertension (systolic blood pressure > 150 or
             diastolic blood pressure > 90 repeatedly).

          -  Known life-threatening hypersensitivity to rituximab or other anti-B cell antibodies.

          -  Inability to comply with the allogeneic transplant treatment.

          -  Uncontrolled central nervous system (CNS) involvement with disease

        Donor Exclusion Criteria:

          -  Identical twin to subject

          -  Contra-indication to subcutaneous G-CSF at a dose of 16 mg/kg/d for 5 consecutive days

          -  Serious medical or psychological illness

          -  Prior malignancy within the preceding five years, with the exception of non-melanoma
             skin cancers.

          -  HIV seropositivity