Study of Veltuzumab and 90Y-Epratuzumab in Relapsed/Refractory, Aggressive NHL

• Status: Withdrawn
• Trial end date: 2017-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this study is to evaluate a new approach to immunotherapy in NHL by combining two antibodies, veltuzumab and epratuzumab. For treatment, epratuzumab has also been attached to a radioactive isotope called 90yttrium (90Y-epratuzumab). Veltuzumab and 90Y-epratuzumab attack different areas on lymphoma cells. Because of this, treatment with the combination may provide more effective treatment in NHL than either veltuzumab or 90Y-epratuzumab given alone.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gilead Sciences; Immunomedics, Inc.
• Treatments: 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; Epratuzumab; Veltuzumab

Criteria

Inclusion Criteria:

• Male or female, >18 years old

• Histological diagnosis of CD20+ B-cell NHL, with DLBCL or other aggressive lymphomas by WHO lymphoma criteria including mantle cell lymphoma and transformed follicular lymphoma.

• Failed at least one prior standard treatment regimen for NHL

• If DLBCL, either received, ineligible for or refused high-dose chemotherapy with stem cell transplant

• Measurable NHL disease by CT, with at least one lesion >1.5 cm in one dimension

• Adequate performance status (>70 Karnofsky scale, 0-1 ECOG)* with an estimated life expectancy of at least 6 months

• Laboratory parameters:

• Adequate hematology (Hemoglobin >/= 10 g/dL, ANC >/= 1.5 ´ 109/L, platelets >/=100 x 109/L) without ongoing transfusional support

• Adequate renal and liver function (creatinine and bilirubinand ALT
• Otherwise,- 3 months beyond any prior rituximab or veltuzumab treatment, 12 weeks beyond autologous stem cell transplant and 4 weeks beyond chemotherapy, other experimental treatments, or any radiation therapy to the index lesion(s).

• Screened for hepatitis B (no time limit) and negative by tests included in NCCN guidelines (hepatitis B surface antigen/antibodies, core antigen/antibodies, hepatitis B e-antigen).

• Patients of childbearing potential must be willing to practice birth control during the study until at least 12 weeks after last veltuzumab infusion; women of childbearing potential must have a negative urine or serum pregnancy test to enter the study.

• Ability to provide signed, informed consent

Exclusion Criteria:

• Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test

• NCI CTC Grade 3 or 4 infusion reaction to prior anti-CD20 antibodies (rituximab, veltuzumab, etc.)

• A known anti-antibody response to prior antiCD20 antibodies (HACA positive, HAHA positive, etc)

• Prior radioimmunotherapy, including Zevalin or Bexxar.

• Prior high-dose chemotherapy with peripheral blood stem cell transplant.

• Prior therapy with other human or humanized monoclonal antibodies, unless HAHA tested and negative

• Primary CNS lymphoma, HIV lymphoma or transformed lymphoma, or presence of symptomatic CNS metastases or carcinomatous meningitis.

• Rituximab or veltuzumab resistant, defined as having progressed during or within 6 months of any prior rituximab or veltuzumab treatment.

• Bulky disease by CT, defined as any single mass >10 cm in its greatest diameter

• Bone marrow involvement ≥25%

• Prior external beam radiation therapy to >30% bone marrow.

• Pleural effusion with positive cytology for lymphoma

• Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive

• Known autoimmune disease or presence of autoimmune phenomena.

• Evidence of infection or requiring antibiotics within 7 days.

• Use of systemic corticosteroids within 2 weeks, except low dose regimens (prednisone, <20 mg/day, or equivalent) which may continue if unchanged.

• Prior malignancies (other than non-melanoma skin cancer or carcinoma in situ of the cervix) unless disease free for 5 years.

• Prior malignancy with less than a 5-year disease-free interval, excluding nonmelanoma skin cancers and carcinoma in situ of the cervix.

• Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations