DT PACE, Tandem Autologous Transplant, Maintenance Therapy for Waldenstrom's Macroglobulinemia Patients
Condition: Waldenstrom Macroglobulinemia
MeSH terms: Waldenstrom Macroglobulinemia
Intervention: DT PACE + Rituxan
Intervention description: INDUCTION PHASE DT PACE + Rituxan DT PACE + Rituxan + PBSC Collection Response Assessment TRANSPLANT PHASE Transplant 1 (MEL 200 (patients with < 50% response to induction) OR MEL-DT PACE (Patients with > 50% response to Induction) Transplant 2 (identical to the first, except patients with progressive or proliferative disease, will receive BEAM) MAINTENANCE PHASE Rituxan every 3 months x 1 year
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Waldenstrom

Summary:

      The purpose of this study is to find out what the response is and the side effects are with
      chemotherapy using a combination of drugs called D.T. PACE (Dexamethasone, Thalidomide,
      cis-Platinum, Adriamycin, Cyclophosphamide, and Etoposide) + Rituxan, followed by two
      autologous transplants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a pathological diagnosis of Waldenstrom's Macroglobulinemia, with
             advanced and/or symptomatic disease requiring therapy. At least one of the following
             must be true: *Presence of cytopenias, defined as Hemoglobin < 11 gm%, or WBC <
             2000/µl, or platelets < 100,000 µl; *Presence of extensive (>3 cm) or symptomatic
             lymphadenopathy or hepatosplenomegaly; *Presence of B symptoms (night sweats, fever,
             weight loss of >10% of the baseline); *Presence of severe neuropathy, not otherwise
             explained; *Progressive disease (increase in "M" by > 50% while observed, and decrease
             in hemoglobin by >2 gm%,and/or decrease in platelets by >50,000/µl, and/or increase in
             lymphadenopathy); *Serum albumin <2.5 gm%; *Persistently elevated β-2M >3.0 in the
             absence of renal impairment or active infection.

          -  Hyperviscosity will be treated (in addition to plasmapheresis) only in the presence of
             any of the above

          -  All necessary baseline studies for determining eligibility must be obtained within 35
             days prior to registration.

          -  Patients must have a performance status of 0-2 based on SWOG criteria. Patients with a
             poor performance status (3-4), based solely on bone pain, will be eligible.

          -  Patients must not have significant co-morbid medical conditions or uncontrolled life
             threatening infection.

          -  Patients with recent (< 6 months) myocardial infarction, unstable angina, difficult to
             control congestive heart failure, uncontrolled hypertension, or difficult to control
             cardiac arrythmias are ineligible. Ejection fraction by ECHO must be > 50% and must be
             performed within 60 days prior to registration, unless the patient has received
             chemotherapy within that period of time (dexamethasone and thalidomide excluded), in
             which case the LVEF must be repeated.

          -  Patients must have a creatinine < 3 mg/dl and a creatinine clearance > 30 ml/minute.
             Patients with a creatinine clearance of 30-50 ml will only receive a 50% cisplatin
             dose.

          -  Patients must have adequate hepatic function defined as serum transaminases < 2 x ULN
             and direct bilirubin < 2.0 mg/dl.

          -  Patients must be able to receive full doses of DT PACE, in the opinion of the treating
             investigator, with the exception of: *Patients that have received prior adriamycin >
             450 mg/m2 and LVEF < 55%. Adriamycin will be omitted in these patients; *Patients with
             a creatinine clearance 30 - 50 ml/minute, who will receive 50% of the cisplatin dose.

          -  Patients must not have a history of chronic obstructive or chronic restrictive
             pulmonary disease. Patients must have adequate pulmonary function studies > 50% of
             predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > 50%
             of predicted. Patients unable to complete pulmonary function tests due to myeloma
             related pain or fracture must have a high resolution CT scan of the chest and must
             also have acceptable arterial blood gases defined as PO2 greater than 70.

        Exclusion Criteria:

          -  No prior malignancy is allowed except for adequately treated basal cell or squamous
             cell skin cancer, in situ cervical cancer, or other cancer for which the patient has
             been disease free for at least three years. Prior malignancy is acceptable provided
             there has been no evidence of disease within the three-year interval.

          -  Pregnant or nursing women may not participate. Women of childbearing potential must
             have a negative pregnancy test documented within one week of registration. Women/men
             of reproductive potential may not participate unless they have agreed to use an
             effective contraceptive method.

          -  All patients must be informed of the investigational nature of this study and must
             sign and give written informed consent in accordance with institutional and federal
             guidelines.