Clinical trial NCT00596804: Safety Study of Different Doses of hA20 (Veltuzumab) in CD20+ Non-Hodgkin's Lymphoma
Official title: A Phase I Study of Immunotherapy With hA20 Administered Once Weekly for 4 Consecutive Weeks in Patients With CD20+ Non- Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin's Lymphoma
Lymphoma, Diffuse
Lymphoma, Diffuse, Mixed Lymphocytic-Histiocytic
Keywords: NHL
Non-Hodgkin's lymphoma
follicular lymphoma
B-cell lymphoma
diffuse large cell lymphoma
small lymphoctytic lymphoma
Mantle cell lymphoma
MALT
marginal zone lymphoma
High-Grade
Intermediate-Grade
Low-Grade
Mixed
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2008-01-17
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is being done to assess the safety and tolerance of different doses of humanized hA20 in patients with NHL.


Eligibility criteria: Inclusion Criteria:

* Male or female, \>18 years old
* Histological diagnosis of CD20+ B-cell NHL (all grades) by WHO lymphoma criteria
* Failed at least one prior standard chemotherapy regimen for NHL
* Failed rituximab treatment for relapsed NHL
* 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
* Adequate hematologic status, without ongoing transfusional support (hemoglobin ≥ 10 g/dL, ANC ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L)
* Adequate renal and hepatic function, defined as: creatinine ≤ 1.5 x Institution Upper Limit of Normal (IULN), bilirubin ≤ 1.5 x IULN, AST and ALT ≤ 2.5 x IULN
* Otherwise, \<Grade 1 toxicity at study entry by NCI CTC version 2.0, including recovery from all acute toxicities incurred as a result of previous surgery, radiotherapy or chemotherapy, whether investigational or conventional.
* At least 6 months beyond previous rituximab treatment, 12 weeks beyond autologous stem cell transplant, 4 weeks beyond chemotherapy, other experimental treatments, or any radiation therapy to the index lesion(s).
* Ability to provide signed, informed consent

Exclusion Criteria:

* Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test
* Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control while enrolled in the study until at least 12 weeks after the last weekly hA20 infusion.
* Rituximab resistant, defined as having progressed during or within 6 months of rituximab treatment.
* Excessive toxicity to rituximab (NCI CTC Grade 3 or 4) or known to be HACA positive
* Prior radioimmunotherapy, including Zevalin or Bexxar,
* 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.
* Bulky disease by CT, defined as any single mass \>10 cm in its greatest diameter
* Pleural effusion with positive cytology for lymphoma Known to be HIV positive, or hepatitis B or C positive
* Known autoimmune disease or presence of autoimmune phenomena.
* Evidence of infection or requiring antibiotics within 5 days.
* Corticosteroid use within 2 weeks
* 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 studyprocedures and follow-up examinations

Primary outcomes:
measure: Safety of hA20 with this administration schedule and dosing
timeFrame: first 12 weeks, then over 2 years
measure: tolerance of hA20 with this administration schedule and dosing
timeFrame: first 12 weeks
measure: immunogenicity of hA20 with this administration schedule and dosing
timeFrame: first 12 weeks, as needed over 2 years
Secondary outcomes:
measure: Pharmacodynamics of hA20
timeFrame: first 12 weeks, then up to 2 years
measure: pharmacokinetics hA20
timeFrame: first 12 weeks, then up to 2 years
measure: assess efficacy
timeFrame: 4 and 12 weeks, then every 3 months for 2 years
Other outcomes:
Locations:
city: Lille
country: France
facility: Service Des Maladies Du Sang
state: Cedex
city: Lyon
country: France
facility: Centre hospitalier Lyon
state: Pierre Benite Cedex
city: Leicester
country: United Kingdom
facility: University of Leicester
Study officials:
affiliation: Gilead Sciences
name: William Wegener, MD, PhD
role: STUDY_CHAIR
References:
citation: Stein R, Qu Z, Chen S, Rosario A, Shi V, Hayes M, Horak ID, Hansen HJ, Goldenberg DM. Characterization of a new humanized anti-CD20 monoclonal antibody, IMMU-106, and Its use in combination with the humanized anti-CD22 antibody, epratuzumab, for the therapy of non-Hodgkin's lymphoma. Clin Cancer Res. 2004 Apr 15;10(8):2868-78. doi: 10.1158/1078-0432.ccr-03-0493.
citation: Stein R, Qu Z, Chen S, Solis D, Hansen HJ, Goldenberg DM. Characterization of a humanized IgG4 anti-HLA-DR monoclonal antibody that lacks effector cell functions but retains direct antilymphoma activity and increases the potency of rituximab. Blood. 2006 Oct 15;108(8):2736-44. doi: 10.1182/blood-2006-04-017921. Epub 2006 Jun 15.
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: Franck Morschhauser1*, John P Leonard2, Bertrand Coiffier3*, et.al. INITIAL SAFETY AND EFFICACY RESULTS OF A SECOND-GENERATION HUMANIZED ANTI-CD20 ANTIBODY, IMMU-106 (HA20), IN NON-HODGKINS LYMPHOMA: ASH abstract 2005.
citation: Morschhauser F, Leonard JP, Coiffier B Petillon M, Coleman M,. Bahkti A, Teoh N, Wegener WA, Goldenberg DM. Phase I/II result of a seoncd-generation humanized anti- CD20 antibody, IMMU-106 (.hA20), in NHL: 2006 ASCO Annual Meeting.Proceedings; 24/18S Part I of II:429s
citation: Morschhauser F, Leonard JP, Fayad L, Coiffier B, Petillon M, Coleman M,. Horne H, Teoh N, Wegener WA, Goldenberg DM. Low doses of humanized anti-CD20 antibody, IMMU-106 (hA20), in refractory or recurrent NHL: Phase I/II results. 2007 ASCO Annual Meeting.Proceedings; 25/18S Part I of II:449s
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.