Clinical trial NCT01101581: Study of Veltuzumab and 90Y-Epratuzumab in Relapsed/Refractory, Aggressive NHL
Official title: Phase I/II Study of Veltuzumab Combined With 90Y-Epratuzumab Tetraxetan in Patients With Relapsed/Refractory, Aggressive Non- Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Non Hodgkin's Lymphoma
NHL
Aggressive NHL
Diffuse Large B-cell Lymphoma
Keywords: Diffuse Large cell NHL
Mantle cell NHL
Lymphoblastic lymphoma
Diffuse mixed cell lymphoma
Diffuse large cell lymphoma
large noncleaved cell lymphoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2010-04-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: The treatment portion of this study consists of study drug administrations each week for four weeks in a row (a total of 4 treatment days). Patients will then return at intervals up to 12 weeks for blood samples and for evaluations to see if their disease responded and to monitor any adverse effects related to treatment. Some blood tests may then need to be repeated at least a few times and/or until any abnormal findings at earlier evaluations have resolved. Otherwise, patients will continue to be evaluated every 3 months for two years, then every 6 months up to 5 years or until the disease worsens. Participation in the study will end when NHL disease worsens.

Eligibility 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 bilirubin \</= 1.5 x IULN; AST and ALT \</= 2.5 x IULN)
* Otherwise, \<Grade 1 toxicity at study entry by NCI CTC version 3.0.
* 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

Primary outcomes:
measure: Safety/dose limiting toxicity
timeFrame: 12 weeks
Secondary outcomes:
measure: Efficacy
timeFrame: 12 weeks-5 years
Other outcomes:
Locations:
city: Newark
country: United States
facility: Helen F. Graham Cancer Center
state: Delaware
city: Orlando
country: United States
facility: MDACC Orlando
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Goshen
country: United States
facility: Goshen Center for Cancer Care
state: Indiana
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Weill Med College of Cornell Univ/NYH
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
Study officials:
affiliation: Gilead Sciences
name: William Wegener, MD, PhD
role: STUDY_CHAIR
References:
citation: Morschhauser F, Leonard JP, Fayad L, Coiffier B, Petillon MO, Coleman M, Schuster SJ, Dyer MJ, Horne H, Teoh N, Wegener WA, Goldenberg DM. Humanized anti-CD20 antibody, veltuzumab, in refractory/recurrent non-Hodgkin's lymphoma: phase I/II results. J Clin Oncol. 2009 Jul 10;27(20):3346-53. doi: 10.1200/JCO.2008.19.9117. Epub 2009 May 18.
citation: Goldenberg DM, Morschhauser F, Wegener WA. Veltuzumab (humanized anti-CD20 monoclonal antibody): characterization, current clinical results, and future prospects. Leuk Lymphoma. 2010 May;51(5):747-55. doi: 10.3109/10428191003672123.
citation: Morschhauser F, Kraeber-Bodere F, Wegener WA, Harousseau JL, Petillon MO, Huglo D, Trumper LH, Meller J, Pfreundschuh M, Kirsch CM, Naumann R, Kropp J, Horne H, Teoh N, Le Gouill S, Bodet-Milin C, Chatal JF, Goldenberg DM. High rates of durable responses with anti-CD22 fractionated radioimmunotherapy: results of a multicenter, phase I/II study in non-Hodgkin's lymphoma. J Clin Oncol. 2010 Aug 10;28(23):3709-16. doi: 10.1200/JCO.2009.27.7863. Epub 2010 Jul 12.