An Open-Label, Multicenter, Phase I Trial of the Safety and Pharmacokinetics of Escalating Doses of DCDS4501A in Patients with Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia and DCDS4501A in Combination with Rituximab in Patients with Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

Completed

Conditions: Chronic Lymphocityc Leukemia
Non-Hodgkin Lymphoma
10024324

Registration Number: NL-OMON39626

Lead Sponsor: Genentech Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

Patients must meet the following criteria to be eligible for study entry:;* Signed Informed Consent Form(s);* Age * 18 years;* ECOG performance status of 0, 1, or 2;* Life expectancy of at least 12 weeks;* History of one of the following histologically-documented hematologic;malignancies that are expected to express the CD79b antigen and for which no suitable therapy of curative intent or higher priority exists (e.g., standard chemotherapy, autologous stem cell transplant): indolent NHL (including Grades 1-3a FL; MZL [including splenic, nodal,;and extra-nodal]; and SLL), Grade 3b FL, DLBCL, MCL, or CLL;For each patient, an archival or fresh biopsy or tumor specimen (e.g., peripheral blood for CLL patients) must be available locally at the study center prior to dosing to be used to evaluate level of CD79b expression retrospectively following central pathology review.;A lymph-node biopsy to evaluate disease transformation is required for patients with clinical suspicion of transformation. Transformed disease is an eligible diagnosis for enrollment in the NHL cohorts, but also must be relapsed/refractory to standard therapies.;Histologic transformation of an indolent lymphoma to an aggressive histology should be evaluated in any patient who has developed rapid progression of lymphadenopathy, infiltration of uncommon extranodal sites (excluding the bone marrow), development of systemic symptoms (e.g., fevers, night sweats, or weight loss), elevated serum lactate;dehydrogenase and/or hypercalcemia, or the emergence of foci of intense uptake on PET scanning (Freedman and Friedberg 2010).;Note: For the initial dose escalation part of the study, only NHL patients will be enrolled. A separate dose escalation will be initiated in CLL;patients once the NHL dose escalation has cleared the 0.5 mg/kg dose level (see Section 3.1.1).;* Have a clinical indication for treatment as determined by the investigator;* All patients (NHL and B-CLL) must have at least one bi-dimensionally measurable lesion (> 1.5 cm in its largest dimension by computerized;tomography [CT] scan). In addition, where appropriate, for CLL patients, circulating lymphocyte cell assessments will be performed.;* Laboratory values (including patients with renal or hepatic involvement due to NHL/CLL), as follows:;AST and ALT * 2.5 × the upper limit of normal (ULN) Total bilirubin * 1.5 × ULN Platelet count * 75,000/mm3 (unless thrombocytopenia clearly due to marrow involvement of NHL/CLL, and/or disease-related immune thrombocytopenia) ;Absolute neutrophil count (ANC) * 1000/mm3 (without growth factor support,;unless neutropenia is clearly due to marrow involvement of NHL/CLL);Total hemoglobin * 9 g/dL (without transfusion support, unless anemia is;clearly due to marrow involvement of NHL/CLL);Serum creatinine * 2.0 mg/dL or measured creatinine clearance * 50 mL/min;* For all men or women of childbearing potential (unless surgically sterile):;use of adequate methods of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly;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.;Use of two forms of effective contraception (e.g., one barrier and one non-barrier method) is required throughout the study and, due to the long half-life of humanized/human m

Exclusion Criteria

-Prior use of any monoclonal antibody or antibody-drug conjugate within 4 weeks before Cycle 1, Day 1;-Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent within 2 weeks prior to Cycle 1, Day 1;Adverse events from any previous treatments must be resolved or stabilized prior to Cycle 1, Day 1, except for neuropathy;-Completion of autologous stem cell transplant within 100 days prior to Cycle 1, Day 1;-Prior allogeneic stem cell transplant;-History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins);- History of other malignancy which 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 history of CNS lymphoma;-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 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 4 weeks prior to Cycle 1, Day 1, other than for diagnosis;-Presence of positive test results for Hepatitis B (Hepatitis B surface antigen [HBsAg] and/or total HB core antibody [anti-HBc]) or Hepatitis C (Hepatitis C virus [HCV] antibody);Patients who are positive for anti-HBc are eligible only if PCR is negative for HBV DNA;Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for the study.;-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 for at least 2 weeks prior to study enrollment and initiation of therapy

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1) To evaluate the safety and tolerability of DCDS4501A administered every 3<br /><br>weeks to patients with relapsed or refractory Non-Hodgkin's Lymphoma and<br /><br>Chronic Lymphocytic Leukemia<br /><br>2) To determine the maximum tolerated dose and dose-limiting toxicities of<br /><br>DCDS4501A when administered every 3 weeks in<br /><br>patients with Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia<br /><br>3) To identify, on the basis of safety, pharmacokinetic, and pharmacodynamic<br /><br>data, a proposed Phase II dose of DCDS4501A for both Non-Hodgkin's Lymphoma and<br /><br>Chronic Lymphocytic Leukemia</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1) Assessment of the incidence of anti-therapeutic antibodies to DCDS4501A.<br /><br>2) Characterize the pharmacokinetics of DCDS4501A in patients with relapsed or<br /><br>refractory Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia.<br /><br>4) Preliminary assessment of the anti-tumor activity of DCDS4501A in patients<br /><br>with relapsed or refractory Non-Hodgkin's Lymphoma and Chronic Lymphocytic<br /><br>Leukemia<br /><br>5) Preliminary assessment of biologic markers that might act as predictors of<br /><br>DCDS4501A anti-tumor activity</p><br>