Safety Study of Different Doses of hA20 (Veltuzumab) in CD20+ Non-Hodgkin's Lymphoma

Non-Hodgkin's Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00596804
• Other study ID #: IM-T-hA20-01EU
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2004
• Est. completion date: November 2007

Study information

• Verified date: February 2012
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: November 2007
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Diffuse
• Lymphoma, Diffuse, Mixed Lymphocytic-Histiocytic
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• veltuzumab
once weekly intravenous dosing for 4 weeks

Locations

Country	Name	City	State
France	Service Des Maladies Du Sang	Lille	Cedex
France	Centre hospitalier Lyon	Lyon	Pierre Benite Cedex
United Kingdom	University of Leicester	Leicester

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

France,  United Kingdom, 

References & Publications (7)

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.

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. Review. — View 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

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.P

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 — View 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. — View 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. Epub 2006 Jun 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of hA20 with this administration schedule and dosing		first 12 weeks, then over 2 years
Primary	tolerance of hA20 with this administration schedule and dosing		first 12 weeks
Primary	immunogenicity of hA20 with this administration schedule and dosing		first 12 weeks, as needed over 2 years
Secondary	Pharmacodynamics of hA20		first 12 weeks, then up to 2 years
Secondary	pharmacokinetics hA20		first 12 weeks, then up to 2 years
Secondary	assess efficacy		4 and 12 weeks, then every 3 months for 2 years