Bortezomib and Chemotherapy in Treating Participants With Lymphoid Malignancies Undergoing Stem Cell Transplant
Condition: CD20 Positive; Hematopoietic and Lymphoid Cell Neoplasm; Lymphocytic Neoplasm; Lymphoma
MeSH terms: Neoplasms
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation; Anti-Thymocyte Globulin; Bortezomib; Carmustine; Cytarabine; Etoposide; Filgrastim; Melphalan; Methotrexate; Rituximab; Tacrolimus
Intervention description: Undergo allogeneic hematopoietic stem cell transplantation; Given IV; Given IV; Given IV; Given IV; Given IV; Given SC; Given IV; Given IV; Given IV; Given IV and PO
Intervention MeSH terms: Cytarabine; Rituximab; Antineoplastic Agents, Immunological; Methotrexate; Etoposide; Etoposide phosphate; Bortezomib; Melphalan; Mechlorethamine; Carmustine; Podophyllotoxin; Nitrogen Mustard Compounds; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Lenograstim; Tacrolimus; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and best dose of bortezomib when given with
      chemotherapy and to see how well they work in treating participants with lymphoid
      malignancies undergoing stem cell transplant. Giving chemotherapy before a stem cell
      transplant helps stop the growth of cells in the bone marrow, including normal blood-forming
      cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused
      into the participant they may help the participant's bone marrow make stem cells, red blood
      cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can
      make an immune response against the body's normal cells called graft versus host disease.
      Giving tacrolimus and methotrexate after the transplant may stop this from happening. Giving
      bortezomib and chemotherapy may work better in treating participants with lymphoid
      malignancies undergoing a stem cell transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Any histological subtype of CD20+ lymphoid malignancies or T-cell lymphoid
             malignancies.

          -  Patients with CD20+ lymphoid malignancies in relapse after failing >= 1 prior regimen
             of conventional treatment and not eligible for non-myeloablative transplant. Patients
             with T-cell lymphoid malignancies can either be in relapse or newly diagnosed with
             high risk features (such as high International Prognostic Index [IPI] of >= 2).

          -  Patients with prior non-myeloablative transplant are eligible if not from the same
             donor.

          -  A fully-matched or one-antigen mismatched sibling or unrelated donor.

          -  Left ventricular ejection fraction (EF) >= 40% with no uncontrolled arrhythmias or
             symptomatic heart disease.

          -  Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and
             diffusion capacity of the lung for carbon monoxide (DLCO) >= 40%.

          -  Serum creatinine < 1.8 mg/dL.

          -  Serum bilirubin < 3 X upper limit of normal.

          -  Serum glutamate pyruvate transaminase (SGPT) < 3 X upper limit of normal.

          -  Voluntary signed, written Institutional Review Board (IRB)-approved informed consent
             before performance of any study-related procedure not part of normal medical care,
             with the understanding that consent may be withdrawn by the subject at any time
             without prejudice to future medical care.

          -  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:

          -  Past history of anaphylaxis following exposure to rituximab or Velcade, boron or
             mannitol.

          -  History of grade 3 or 4 National Cancer Institute (NCI) toxicity with prior Velcade
             therapy.

          -  Patient with active central nervous system (CNS) disease.

          -  Pregnant (positive beta human chorionic gonadotropin [HCG] test in a woman with child
             bearing potential defined as not post-menopausal for 12 months or no previous surgical
             sterilization) or currently breast feeding. Pregnancy testing is not required for
             post-menopausal or surgically sterilized women.

          -  Known infection with human immunodeficiency virus (HIV), human T-lymphotropic virus
             (HTLV-I), hepatitis B, or hepatitis C.

          -  Patients with other malignancies diagnosed within 2 years prior to study day -13
             (except skin squamous or basal cell carcinoma).

          -  Active uncontrolled bacterial, viral or fungal infections.

          -  Major surgical procedure or significant traumatic injury within 4 weeks prior to day
             -13.

          -  Serious, non-healing wound, ulcer, or bone fracture.

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 3 months prior to day -13.

          -  History of stroke within 6 months.

          -  Myocardial infarction within the past 6 months prior to study day 1, or has New York
             Heart Association (NYHA) class III or IV heart failure or arrhythmia, unstable angina,
             uncontrolled congestive heart failure or arrhythmias, or electrocardiographic evidence
             of acute ischemia or active conduction system abnormalities. Prior to study entry, any
             electrocardiography (ECG) abnormality at screening must be documented by investigator
             as not medically relevant.

          -  Uncontrolled hypertension (>= 140/90).

          -  Uncontrolled chronic diarrhea.

          -  A prior allogeneic transplant from the same donor.

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.

          -  Patient has received other investigational drugs within 3 weeks before enrollment.

          -  Active peripheral neuropathy greater or equal to grade 2.