Phase 2 Study of Zevalin Versus Zevalin and Motexafin Gadolinium in Patients With Rituximab-Refractory Low-grade or Follicular B-cell Non-Hodgkin's Lymphoma
Condition: Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell
Intervention: Y-90-Zevalin; Moxtezafin Gadolinium; Rituximab
Intervention description: Day 8 - Y-90-Zevalin 0.4 mCi/kg 10-minute intravenous push; Day 1-4 Motexafin gadolinium 5 mg/kg intravenously once daily, followed in one hour (Day 1 only) by Day 1 Rituximab 250 mg/m^2 intravenous infusion.
Day 8-11 Motexafin gadolinium 5 mg/kg intravenously once daily; Day 1 and Day 8: Rituximab 250 mg/m^2 intravenous infusion
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Hodgkin's Lymphoma; Zevalin; Motexafin Gadolinium

Summary:

      The objectives of this study are to evaluate the efficacy and safety of the Zevalin regimen
      compared to Zevalin and motexafin gadolinium in patients with rituximab-refractory, low-grade
      or follicular Non-Hodgkin's Lymphoma (NHL).

      Effectiveness of the experimental regimen assessed by complete response rate within 6 months
      of study entry (primary endpoint), complete response rate within 3 months of study entry, and
      overall response rate within 6 month of study entry.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Men or women, at least 18 years of age

          2. Histologically-confirmed follicular or indolent, marginal zone and small lymphocytic B
             cell non-Hodgkin's lymphoma

          3. Progressive disease within 6 months of the end of a rituximab-containing regimen; or
             progressive disease at any time following 2 or more prior rituximab-containing
             regimens; or progressive disease while on rituximab-containing regimen.

          4. At least 1 measurable tumor (> 1.5 cm in the long axis and > 1.0 cm in the short axis)
             that has not been irradiated previously or that has increased in size since previous
             irradiation

          5. A life expectancy of at least 3 months

          6. A World Health Organization/Eastern Cooperative Oncology Group (WHO/ECOG) performance
             status of 0 or 1

          7. Adequate hematopoietic function: absolute neutrophil count (ANC) ≥ 1,500 cells/μL,
             absolute lymphocyte count (ALC) ≤ 5,000 cells/μL, platelet count ≥ 100,000
             cells/μL,hemoglobin ≥ 9 g/dL (may be transfused to maintain this concentration).
             Patients who have received pre-phase therapy for purposes of improving performance
             status prior to initiating Zevalin are eligible.

          8. Adequate liver function: total bilirubin ≤ 2 × upper limit of normal (ULN), Aspartate
             aminotransferase (AST) (Serum glutamic oxaloacetic transaminase [SGOT]) and Alanine
             transaminase (ALT) (Serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper limits
             of normal (ULN)

          9. Creatinine clearance ≥ 60 mL/min/1.73 m^2

         10. Bone marrow involvement < 25%

         11. If men or women of reproductive potential, agree to use adequate contraception
             (hormonal or barrier method of birth control) prior to study entry and for at least 1
             year following treatment with Zevalin

         12. Willing and able to provide written Informed Consent and to comply with the
             requirements of the study protocol

        Exclusion Criteria:

          1. Received antineoplastic, experimental, and/or radiation therapy within the 3 weeks
             prior to Study Day 1

          2. Has not recovered to ≤ Grade 1 from all toxicities related to prior treatments

          3. Prior radioimmunotherapy for NHL

          4. Autologous stem cell transplant within the 3 months prior to Study Day 1, and/or any
             history of allogeneic stem cell transplant with continued allogeneic hematopoiesis

          5. Platelet transfusion within the 7 days prior to Study Day 1

          6. History of porphyria

          7. Grade 2 or higher peripheral neuropathy within the 14 days prior to Study Day 1

          8. History of or active central nervous system disease (e.g., primary brain tumor,
             seizures not controlled with standard medical therapy, brain metastases)

          9. Ongoing, active infection that requires anti infective therapy

         10. Clinically significant cardiovascular disease (e.g., unstable angina pectoris, serious
             cardiac arrhythmia requiring medication, uncontrolled hypertension, myocardial
             infarction, New York Heart Association [NYHA] Class 2 or higher congestive heart
             failure, Grade 2 or higher peripheral vascular disease) within the 12 months prior to
             Study Day 1

         11. History of another clinically significant medical condition, metabolic dysfunction,
             physical examination finding, and/or clinical laboratory finding giving reasonable
             suspicion of a disease or condition that contraindicates use of an investigational
             drug or that might affect interpretation of the results of the study or place the
             patient at high risk of treatment complications and/or of noncompliance with the study
             procedures

         12. Major surgical procedure and/or significant traumatic injury (that which could
             interfere with the patient's ability to receive protocol therapy as determined by the
             principal investigator) within the 28 days prior to Study Day 1, and/or patient is
             anticipated to require a major surgical procedure during the study period

         13. Diagnosed with and/or treated for a malignancy other than NHL within the 2 years prior
             to Study Day 1, with the exception of complete resection of basal cell carcinoma or
             squamous cell carcinoma of the skin, an in situ malignancy, and/or low-risk prostate
             cancer after curative therapy from which the patient has been disease-free for at
             least 1 year

         14. Evidence of a bleeding diathesis and/or a coagulopathy

         15. Known HIV infection

         16. Known hypersensitivity to drugs with porfyrin-like structures, like Visudyne™.

         17. Positive Hepatitis B or C infection: Patient must be tested for hepatitis B surface
             antigen.

         18. Pregnant or lactating woman

         19. Full dose oral or parenteral anticoagulants within the 10 days prior to Study Day 1,
             and/or anticipated full dose oral or parenteral anticoagulant therapy during the study
             period(except as required to maintain patency of pre-existing, permanent, indwelling
             intravenous catheters) or thrombolytic agents

         20. Participated in another clinical study within the 4 weeks prior to Study Day 1