Thalidomide, Lenalidomide, and Rituximab for Previously Treated Waldenstrom Macroglobulinemia
Condition: Waldenstrom Macroglobulinemia
MeSH terms: Waldenstrom Macroglobulinemia
Intervention: Thalidomide; Lenalidomide; Rituximab
Intervention description: Thalidomide 50 mg (every ODD day of a 28 day cycle: Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 & 27); Lenalidomide (every EVEN day of a 28 day cycle: Days 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 & 28). Lenalidomide will be initiated at a starting dose of 5 mg.; Rituximab 375 mg/m2 IV on Days 1, 8, 15 and 22 (+/- 2 days) and then again on the same weekly x 4 schedule every 6th cycle thereafter (Cycle 7, 13, 19, etc).
Intervention MeSH terms: Thalidomide; Rituximab; Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: WM

Summary:

      The purpose of this study is to evaluate the efficacy and safety of daily alternating
      thalidomide and lenalidomide plus rituximab (ThRiL) in patients with previously treated
      Waldenstrom macroglobulunemia (WM). Thalidomide and lenalidomide are drugs that modulate the
      immune system and have been shown to bring about responses in subjects with WM. However,
      their use has been limited due to side effects. The investigators hypothesize that
      alternating doses of thalidomide and lenalidomide may alleviate the side effects while
      preserving the effectiveness of the therapies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of WM

          -  At least one prior systemic therapy

          -  Measurable disease, defined as quantifiable monoclonal IgM > 1000 mg/dL

          -  Active disease requiring therapy defined as at least one of the following five
             criteria:

               1. Rising IgM

               2. Hemoglobin < 20 g/dL

               3. Platelet count < 100 x 109/L

               4. Symptomatic or bulky lymphadenopathy or organomegaly

               5. Systemic manifestations of WM, including hyperviscosity, neuropathy, amyloidosis,
                  cryoglobulinemia, B symptoms.

          -  note: subjects with symptomatic hyperviscosity or a serum viscosity of > 3.5 CP are
             eligible but should undergo plasmapheresis prior to initiation of treatment

          -  Understand and voluntarily sign an informed consent form

          -  Age >18 years at the time of signing the informed consent form

          -  Able to adhere to the study visit schedule and other protocol requirements

          -  ECOG performance status ≤ at study entry

          -  Laboratory test results within these ranges:

               1. Absolute neutrophil count ≥ 1000/mm³

               2. Platelet count ≥ 50,000/mm³

               3. Creatinine clearance of ≥ 30 mL/min by Cockroft-Gault formula.

               4. Total bilirubin ≤ 1.5 times the ULN, unless abnormality is the result of
                  Gilbert's disease or the result of the WM

               5. AST (SGOT) and ALT (SGPT) ≤ 3 x ULN

          -  Disease free of prior malignancies for ≥ 2 years with exception of curatively treated
             basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma "in situ" of
             the cervix or breast.

          -  All study participants must be registered into the mandatory RevAssist ® (RASP:
             RevAssist ® for Study Participants) and S.T.E.P.S. ® (P-TAP: Protocol Therapy
             Assistant Program) programs and be willing and able to comply with the requirements of
             RevAssist ® and S.T.E.P.S. ®.

          -  Females of childbearing potential (FCBP)† must have a negative serum or urine
             pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to
             and again within 24 hours of starting treatment and again within 24 hours before the
             first dose of lenalidomide AND thalidomide. FCBP must either commit to continued
             abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
             control, one highly effective method and one additional effective method AT THE SAME
             TIME, at least 28 days before she starts taking lenalidomide and/or thalidomide. FCBP
             must also agree to ongoing pregnancy testing. Men must agree to use a latex condom
             during sexual contact with a FCBP even if they have had a successful vasectomy. All
             subjects must be counseled at a minimum of every 28 days about pregnancy precautions
             and risks of fetal exposure. See Appendix A: Risks of Fetal Exposure, Pregnancy
             Testing Guidelines and Acceptable Birth Control Methods.

          -  Able to take aspirin 81 or 325 mg daily or low molecular weight heparin as
             prophylactic anticoagulation, unless already on therapeutic anticoagulation. Subjects
             intolerant to ASA may use warfarin or low molecular weight heparin.

        Exclusion Criteria:

          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from providing informed consent.

          -  Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study.

          -  Concurrent use of other anti-cancer agents or treatments

          -  Prior treatment with thalidomide or lenalidomide

          -  Active serious infection not controlled with antibiotics

          -  Autoimmune hemolytic anemia or thrombocytopenia requiring treatment

          -  Known positive for HIV

          -  Active infection with hepatitis B, defined by being positive for HepBsAg or Hep B DNA
             by PCR, or hepatitis C

          -  Pre-existing peripheral neuropathy > grade 2

          -  Pregnant or breast-feeding females. (Lactating females must agree not to breast feed
             while taking lenalidomide and/or thalidomide).

          -  Disease transformation to an aggressive histology

          -  Treatment for WM within the past 28 days

          -  Hypersensitivity to rituximab