Zevalin/BEAM/Rituximab vs BEAM/Rituximab With or Without Rituximab in Autologous Stem Cell Transplantation
Condition: Diffuse Large Cell Lymphoma; Lymphoma
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Intervention: Zevalin; Carmustine; Etoposide; Cytarabine; Melphalan; Rituximab; Stem Cell Transplant
Intervention description: (111In Zevalin) 5 millicurie (mCi) by vein and (90Y Zevalin) 0.4 mCI/kg by vein.; 300 mg/m^2 by vein.; 200 mg/m^2 by vein every 12 hours.; 200 mg/m^2 by vein every 12 hours.; 140 mg/m^2 by vein.; Arm 1, Arm 2 = 250 mg/m^2 by vein;
Arm 1, Arm 2, Arm 3, Arm 4 = 1000 mg/m^2 by vein following Stem Cell Transplant;
Arm 1, Arm 3 = 375 mg/m² by vein Maintenance Therapy.; Injection of stem cells (Autologous SCT)
Intervention MeSH terms: Cytarabine; Rituximab; Etoposide; Melphalan; Carmustine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Diffuse Large Cell Lymphoma; Lymphoma; Zevalin; Ibritumomab; IDEC-Y2B8; Carmustine; BCNU; BiCNU; Etoposide; VePesid; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine arabinosine hydrochloride; Melphalan; Rituximab; Rituxan; BEAM

Summary:

      The goal of this clinical research study is to learn if the addition of 90Y Zevalin to BEAM
      chemotherapy (carmustine, etoposide, cytarabine, and melphalan) and rituximab is more
      effective than the combination of BEAM and rituximab alone in patients with lymphoma who
      receive a stem cell transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Relapsed CD20-positive B-cell diffuse large cell lymphoma (demonstrated in lymph nodes
             or bone marrow), chemosensitive (at least PR).

          2. Age: up to 18-70 years of age.

          3. Prestudy performance status of 0, 1, or 2 according to the WHO.

          4. No anti-cancer therapy started within three weeks, prior to study initiation, and
             fully recovered from all toxicities associated with prior surgery, radiation
             treatments, chemotherapy, or immunotherapy. No prior rituximab within three weeks of
             starting therapy.

          5. If patients had prior radiation, this should have not involved more than 25% of the
             bone marrow.

          6. Acceptable hematologic status within two weeks prior to patient registration,
             including: Absolute neutrophil count ({segmented neutrophils + bands} x total WBC) >
             1,500/mm³ and platelet counts > 80,000/mm³

          7. IRB -approved signed informed consent.

          8. Patients determined to have <10% bone marrow involvement with lymphoma within 60 days
             before study entry as defined by bone marrow aspirates and biopsies.

          9. Female patients included must not be pregnant or lactating.

         10. Patients should have at least 4-6 x 10^6 CD34+/kg peripheral stem cells collected.
             Around 1-2 million cells will beheld as back up.

         11. Voluntary signed, written 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.

         12. 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:

          1. Failed stem cell collection of >/= 4x10^6CD34+/kg.

          2. Prior radioimmunotherapy.

          3. Presence of active CNS lymphoma.

          4. Patients with abnormal liver function: total bilirubin > 1.5 mg/dl.

          5. Patients with abnormal renal function: serum creatinine > 1.6 mg/dl.

          6. Serious nonmalignant disease or infection which, in the opinion of the investigator
             and/or the sponsor, would compromise other protocol objectives.

          7. Corrected DLCO < 50% and FEV subscript 1 or FVC < 50% predicted.

          8. Cardiac EF < 50% by 2-D Echogram.

          9. Prior radiation to lungs.

         10. Abnormal cytogenetics predictive of secondary cancers, such as -5,-7.

         11. Pregnant (Positive Beta 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.

         12. Patients with other malignancies diagnosed within 2 years prior to Study entry (except
             skin squamous or basal cell carcinoma).

         13. Active uncontrolled bacterial, viral fungal infections.

         14. Major surgical procedure or significant traumatic injury within 4 weeks prior to Study
             entry.

         15. Serious, non-healing wound, ulcer, or bone fracture.

         16. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
             within 3 months prior to Study entry.

         17. History of Stroke within 6 months.

         18. 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 arrythmias, unstable angina,
             uncontrolled congestive heart failure or arrythmias, or electrocardiographic evidence
             of acute ischemia or active conduction system abnormalities. Prior to study entry, any
             ECG abnormality at screening must be documented by investigator as not medically
             relevant.

         19. Uncontrolled chronic diarrhea.

         20. Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.