Rituximab and Autologous Effector Lymphocytes in Non-Hodgkin Follicular Lymphoma in Response to First Line Chemotherapy

NCT01329354 | Unknown Phase 2

• 2 other identifiers: LFNK2009-017829-19
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Nowadays, therapy with monoclonal antibodies is considered to be a standard treatment that increases the rate of remissions and the overall survival in patients with follicular lymphoma. Nevertheless there are an important number of patients who do not benefit from this therapy. A way to improve the efficiency of monoclonal antibodies therapy could be to improve the activity of the effector arm of the immune system. A strategy that has been proposed to obtain this improvement is the utilization of lymphocyte activated killer (LAK) cells. In addition, the combination of LAK cells with monoclonal antibodies might obtain an additive effect across the stimulation of the antibody dependent cellular cytotoxicity (ADCC)activity. The present clinical assay proposes to study the feasibility, safety and effectiveness of treatment with autologous effector cells expanded ex vivo associated with a standard maintenance treatment with rituximab in patients with follicular lymphoma in remission after first-line treatment. In addition, we plan to analyse various biological parameters that can predict the susceptibility of patients to treatment with rituximab. Specifically, we propose to study the polymorphisms of Fc receptor, polymorphisms related to the ability of complement activation, to study both the complement activity and peripheral blood cell subpopulations that can mediate directly or indirectly dependent antibody cytotoxic effect. We will also try to correlate any of these biological parameters with the response to treatment.

Conditions

Follicular Lymphoma; Follicular Non-Hodgkin´s Lymphoma; Autologous Effector Lymphocytes

Keywords

Follicular lymphoma; Follicular non-Hodgkin´s lymphoma; Autologous effector lymphocytes; Cell Therapy; Maintenance therapy; Rituximab

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) from the entry in the study.

  The PFS is defined as the time from the entry in the study up to the progression of the disease.

  01/03/2015

Secondary Outcomes (4)

• Event free survival from the entry in the study

  01/03/2015

• Time to the next anti-lymphoma treatment

  01/03/2015

• Disease free survival

  01/03/2015

• Safety

  01/01/2012

Study Arms (1)

Autologous effector lymphocytes

EXPERIMENTAL

Biological: Autologous effector lymphocytes expanded ex-vivo

Interventions

Autologous effector lymphocytes expanded ex-vivo BIOLOGICAL

Maintenance therapy with Rituximab every two months is the standard of care for patients with follicular lymphoma after induction therapy. The intervention consists on the administration of autologous effector lymphocytes expanded ex-vivo every two Rituximab administrations.

Also known as: LAK, LAK cells, Activated lymphocytes

Autologous effector lymphocytes

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically-confirmed follicular lymphoma CD20-positive grade 1, 2 ó 3a.
• Patients with aptitude to sign the written informed consent and to express his desire to fulfill all the requirements of the protocol during the period of study.
• Patients not treated before. The induction treatment with rituximab and chemotherapy must be the first line for the patients who are included in the study.
• Patients undergoing maintenance therapy with rituximab every two/three months.
• Ann Arbor stage II, III o IV before receiving the induction treatment with rituximab and chemotherapy.
• The patient must have achieved a partial or complete response based on the revised International Workshop Response Criteria (IWRC) (Cheson, et al 2007) following the induction treatment.
• Age \>18 years and \<75 years.
• Performance status \<2 following the Eastern Cooperative Oncology Group (ECOG).
• Screening laboratory values obtained 28 days before registry (unless due to lymphoma involvement of the bone marrow): Hemoglobin \> 8,0 g/dL (5,0 mmol/L), Neutrophil absolute count \> 1,5 x 109/L,Platelets \> 100 x 109/L

You may not qualify if:

• Patients with transformed follicular lymphoma into diffuse large B-cell lymphoma.
• Patients with evidence of follicular lymphoma grade 3b.
• Patients with evidence of primary cutaneous or gastrointestinal follicular lymphoma.
• Patients with evidence of current central nervous system involvement.
• Patients who received previous induction treatment other than rituximab and chemotherapy.
• Patients receiving chronic immunosuppressive agents in the last 4 weeks. Patients may be receiving stable chronic doses of corticosteroids with a maximum dose of 20 mg/day of prednisone or equivalent.
• Patients who have a history of another primary malignancy \< 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix.
• Decompensated renal function: serum creatininea \> 2,0 mg/dL (197 u.mol/L.
• Decompensated hepatic function: total bilirrubine \> 2,0 mg/dL (34 umol/L), AST (SGOT) \> 3 x ULN, unless due to lymphoma involvement
• Patients with a known history of human immunodeficiency virus (HIV) seropositivity, chronic hepatitis or other active viral infections due to hepatitis B virus (HBV) or hepatitis C virus (HVC).
• Patients with underlying serious diseases that in the criteria of the investigator could concern the capacity of the patient to take part in the test (for example, infection in process, not controlled diabetes mellitus, gastric ulcers, autoimmune active disease).
• Life expectancy \<6 months.
• Female patients who are pregnant or breast feeding.
• Patients with known hypersensitivity to rituximab or other murine proteins or to any of the excipients.
• Patients who are using other investigational agents or who have received investigational drus 30 days prior to study drug start.

Sponsors & Collaborators

• Clinica Universidad de Navarra, Universidad de Navarra: lead
• Spanish National Health System: collaborator

Study Sites (1)

Carlos Panizo

Pamplona, Navarre, 31008, Spain

Location

Related Publications (1)

• Garcia-Munoz R, Lopez-Diaz-de-Cerio A, Feliu J, Panizo A, Giraldo P, Rodriguez-Calvillo M, Grande C, Pena E, Olave M, Panizo C, Inoges S. Follicular lymphoma: in vitro effects of combining lymphokine-activated killer (LAK) cell-induced cytotoxicity and rituximab- and obinutuzumab-dependent cellular cytotoxicity (ADCC) activity. Immunol Res. 2016 Apr;64(2):548-57. doi: 10.1007/s12026-015-8747-9.

  PMID: 26659089 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

CD83 protein, human

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2011
• First Posted: April 5, 2011
• Study Start: March 1, 2011
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2019
• Last Updated: October 24, 2017

Record last verified: 2017-10

Locations

ES (1)