Lymphoma and Multiple Myeloma

Previously untreated, histologically confirmed follicular NHL. No prior therapoy for NHL including chemotherapy, radiation, or immunotherapy (e.g., monoclonal antibody-based therapy).

Treatment on this study will consist of two parts:
1) Induction Therapy
2) Extended Induction Therapy
Induction therapy will consist of two drugs epratuzumab + rituximab.
Extended Induction Therapy - Following Induction Therapy, the combination of epratuzumab and rituximab will be given every other month to cover a total of nine months (that is, during months 3, 5, 7 and 9).

Patients will be randomized to one of the following two treatment arms:

Arm A: Lenalidomide Alone
The starting dose of lenalidomide will be 15 mg/day PO on days 1-21 followed by 7 days of rest. After cycle 2, the dose will be escalated in patients who have not had therapy delayed and who have recovered from previous toxicity. Maximum dose will be 25 mg/day. In the absence of intolerable toxicity or disease progression, lenalidomide will be given for a total of twelve cycles.

Arm B: Rituximab + Lenalidomide
Lenalidomide will be administered same as stated in Arm A. Rituximab will be administered at a dose of 375 mg/m2 by IV on Days 8, 5, 22 and 29 beginning one week after initiation of lenalidomide. Patients will receive four weekly infusions of rituximab, and twelve cycles of lenalidomide.

Restaging for both Arms will be during months 2, 4, 6, 9, 12, 15, 18, and 24, and then yearly until disease progression or for a maximum of ten years from study entry.

Patients will be randomized to one of two treatment arms:
Arm A - Patients will receive R-CHOP Chemotherapy
Arm B - Patients receive dose-adjusted EPOCH-R Chemotherapy

Adult subjects with histologic diagnosis of diffuse large B-cell lymphoma who have progressed or relapsed since the most receive therapy. Subjects must have received at least one prior combination chemotherapy regimen.
There is no limit on the number of prior therapies.

Histologically confirmed mantle cell or diffuse large B-cell lymphoma receiving at least one prior systemic therapy. DLBCL patients are not eligible if they received bortezomib.

Patients will receive: Vorinostat 400 mg (total daily dose as a single dose) on days 1-5 and 8-12. Bortezomib 1.3 mg/m2/d IV on days 1, 4, 8, and 11.

Regimen is repeated every 3 weeks.

Patients who experience a complete or partial response following at least one year of treatment may go off study treatment but remain on study and resume study treatment upon disease progression if the study remains open.

Histologically confirmed diagnosis of mantle cell Non-Hodgkin’s Lymphoma with characteristic immunophenotypic profile: CD5(+), CD19(+) or CD20(+), cyclin D1(+), CD23(-) and CD10(-)

Patient has not received any prior anti-cancer therapy for lymphoma.

Bevacizumab will be administered at 15 mg/kg on day 1 of each of 6 cycles. Rituximab will be administered 375 mg/m2 on day 3 of each of 6 cycles (with usual premedications). Standard CHOP chemotherapy will be administered on day 3 every 21 days (full dose) for 6 cycles of treatment.

Once completed six cycles of therapy (~18 weeks), patients will be evaluated every 3 months
for the first year post treatment, then every 6 months until disease progression. Patients who have disease progression will be contacted every 6 months to assess for survival status.

Induction Phase: Rituximab once weekly during Weeks 1 - 4; PEPC daily during Weeks 1 - 12

Maintenance Phase: Rituximab once weekly during Weeks 17 - 20 and 33 - 36; PEPC daily during Weeks 13 - 48

Post-Month 12 Maintenance Phase (until disease progression): Rituximab once weekly during Weeks 1 - 4; PEPC daily during Weeks 1 - 16

PEPC - Prednisone 20 mg/day, Cyclophosphamide 50 mg/day, Etoposide 50 mg/day, and Procarbazine 50 mg/day

Histologic diagnosis of any of the following: Peripheral T-cell lymphoma not otherwise specified (PTCL-U) (IPI >2), Angioimmunoblastic T-cell lymphoma (IPI >2), Non-primary cutaneous Alk-1-negative anaplastic large cell lymphoma, Extranodal NK/T lymphoma (Excluding stage I/II nasal disease), Blastic NK cell lymphoma, Enteropathy type T-cell lymphoma, Subcutaneous panniculitis-like T-cell lymphoma, Hepatosplenic ?d T-cell lymphoma

Patients who test positive for HepBSAg or HepC Ab may be eligible.

Patients will experience five (5) treatment regimens:

Treatment 1: Two 21-day cycles of Gemcitabine, Navelbine, and Doxil.

Treatment 2: Two 21-day cycles of Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, Methotrexate

Treatment 3 - Consolidation: Cytarabine,
Etoposide, CIVI, Denileukin Diftitox (Ontak®),
G-CSF, Stem cell collection

Treatment 4 - Autologous Stem Cell Transplant:
BCNU, Etoposide, Cyclophosphamide,
Stem cell infusion

Treatment 5 - Post-transplant: Denileukin Diftitox (Ontak®)

Adult subjects with histologically confirmed CD30-positive hematologic malignancy and have failed systemic chemotherapy as induction therapy for advanced stage disease or salvage therapy after initial radiotherapy and refused or were ineligible for stem cell transplant.

SGN-35 will be administered on Day 1 of each 21 day cycle via a 2-hour intravenous infusion according to the dose level assigned to each cohort.

hLL1 (humanized anti-CD74 monoclonal antibody) administered intravenously daily, five days
per week (Monday to Friday), for two weeks at one of 4 planned dose levels. Treatment occurs over 2 weeks
with post-treatment evaluations over 12 weeks. Follow-up is required in all patients until resolution of any treatment related abnormalities or until relapse occurs.

CLL patients who are refractory to or relapsed after at least 2 prior therapies, including fludarabine, alone or in combination.

Patients must be symptomatic.

The study drug should be taken twice a day. The patient should take the morning dose with water on an empty stomach; food can be consumed at least an hour after dosing. The evening dose should be taken with water approximately 12 hours after the morning dose and at least 2 hours after a meal.

Each patient will be assessed for clinical response after completing 1 cycle of 28 days of treatment. Treatment may continue for up to a total of 6 cycles.

Diffuse large cell lymphoma; previous indolent lymphoma with transformation to diffuse large B-cell lymphoma at relapse; peripheral T-cell lymphoma; anaplastic large cell lymphoma (ALCL); small non-cleaved Burkitt-like lymphoma.

Salvage Therapy:
Randomization #1 - (R)-GDP or (R)-DHAP. Patients with CD20+ B cell lymphoma will also receive rituximab.

Maintenance Therapy:
Randomization #2 - Rituximab or observation.