A randomized, open-label, multicenter, phase II trial evaluating the safety and activity of DCDT2980S in combination with rituximab or DCDS4501A in combination with rituximab in patients with relapsed or refractory B-cell non Hodgkin's lymphoma.

Signed Informed Consent Form(s)
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status
of 0, 1, or 2
• Life expectancy of at least 12 weeks
• History of histologically documented relapsed or refractory Grades 1*3a FL,
or relapsed or refractory DLBCL
• Availability of an archival or freshly biopsied tumor tissue sample must be
confirmed for study enrollment.
• Have a clinical indication for treatment as determined by the investigator
• Must have at least one bi-dimensionally measurable lesion (> 1.5 cm in its
largest dimension by CT scan or MRI)
• Laboratory values (including patients with hepatic or renal involvement), as
follows:
AST and ALT <= 2.5 × the upper limit of normal (ULN)
Total bilirubin <= 1.5 × ULN
Protocol: DCDT2980S and DCDS4501A*Genentech, Inc.
54/P GO27834
Platelet count >= 75,000/mm3 (unless thrombocytopenia clearly due to
marrow involvement of NHL, and/or disease-related immune
thrombocytopenia)
Absolute neutrophil count >= 1000/mm3 (without growth factor support,
unless neutropenia clearly due to marrow involvement of NHL)
Total hemoglobin >= 9 g/dL (without transfusion support >14 days prior to
screening, unless anemia clearly due to marrow involvement of NHL)
Serum creatinine <= 2.0 mg/dL or measured creatinine clearance >= 50 mL/min

Prior use of any monoclonal antibody, radioimmunoconjugate or antibodydrug
conjugate within 4 weeks before Cycle 1, Day 1
• Treatment with radiotherapy, chemotherapy, immunotherapy,
immunosuppressive therapy, or any investigational anti-cancer agent within
2 weeks prior to Cycle 1, Day 1
Adverse events except for sensory neuropathy from any previous
treatments must be resolved or stabilized to Grade <= 2 prior to Cycle 1,
Day 1
• Completion of autologous stem cell transplant within 100 days prior to
Cycle 1, Day 1
• Prior allogeneic stem cell transplant
• Eligibility for autologous SCT (patients with relapsed or refractory DLBCL)
• History of transformation of indolent disease to DLBCL
• History of severe allergic or anaphylactic reactions to monoclonal antibody
therapy (or recombinant antibody-related fusion proteins)
• History of other malignancy that could affect compliance with the protocol or
interpretation of results
Patients with a history of curatively treated basal or squamous cell
carcinoma of the skin or in situ carcinoma, e.g. of the cervix or breast, are
allowed. Patients with a malignancy that has been treated with curative
intent will also be allowed if the malignancy has been in remission without
treatment for >= 2 years prior to Cycle 1, Day 1.
• Current or past history of CNS lymphoma
• Current Grade > 1 peripheral neuropathy
Evidence of significant, uncontrolled concomitant diseases which could affect
compliance with the protocol or interpretation of results, including significant
cardiovascular disease (such as New York Heart Association Class III or
IV cardiac disease, myocardial infarction within the last 6 months,
unstable arrhythmias, or unstable angina) or significant pulmonary disease
(including obstructive pulmonary disease and history of bronchospasm)
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other
infection (excluding fungal infections of nail beds) at study enrollment, or any
major episode of infection requiring treatment with IV antibiotics or
hospitalization (relating to the completion of the course of antibiotics) within
4 weeks prior to Cycle 1, Day 1
• Recent major surgery within 6 weeks prior to Cycle 1, Day 1, other than
for diagnosis
• Presence of positive test results for Hepatitis B (HBsAg and/or total
Hepatitis B core antibody [anti-HBc]) or Hepatitis C (HCV antibody)
Patients who are positive for anti-HBc are eligible only if PCR is negative
for HBV DNA and it is believed by both the investigator and Medical
Monitor to be in the patient*s best interest to participate.
Patients who are positive for HCV antibody must be negative by for HCV
by PCR to be eligible for study participation
• Known history of HIV seropositive status
• Women who are pregnant or lactating
• Ongoing corticosteroid use > 30 mg/day prednisone or equivalent
Patients receiving corticosteroid treatment <= 30 mg/day prednisone or
equivalent must be documented to be on a stable dose prior to study
enrollment and initiation of therapy
• For female patients of childbearing potential and male patients with female
partners of childbearing potential, agreement to use one highly effective form
of non-hormonal contraception or two effective forms of non-hormonal
contraception through the course of study treatment and for at least 3 months
after the last dose of DCDT2980S or DCDS4501A or rituximab (whichever is
later) in women and at least 5 months after the last dose of DCDT2980S or
DCDS4501A or rituximab (whichever is later) in men.
A woman is considered not to be of childbearing potential if she is
postmenopausal, defined by amenorrhea of >= 12 months duration and age
>= 45 years, or has undergone hysterectomy and/or bilateral oophorectomy.
The following are considered highly effective forms of contraception:
1) true abstinence; 2) male sterilization (with post-procedure
documentation of absence of sperm in the ejaculate). For female patients,
the sterilized male partner should be the sole partner.
The following are considered effective forms of contraception:
1) intrauterine device (copper IUD or hormonal IUDs only) or intrauterine
system; 2) condom with spermicidal foam/gel/film/cream/suppository;
3) occlusive cap (diaphragm or cervical/vault cap) with spermicidal
foam/gel/film/cream/suppository.
Males must agree to abstain from sperm donation for at least 5 months
after the last dose of DCDT2980S or DCDS4501A or rituximab
(whichever is later).