Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD

An Open-label, Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of Chronic Graft Versus Host Disease After TLI/ARG Nonmyeloablative Allogeneic Stem Cell Transplantation

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

To test if prophylactic anti-B-cell therapy (weekly rituximab) given within 60 to 90 days after allogeneic transplantation will decrease allogeneic donor B-cell immunity and possibly the incidence of chronic graft-vs-host disease (cGvHD).

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