Pilot Study of Autologous T Lymphocytes With ADCC in Patients With CD20-Positive B-Cell Malignancies
|ClinicalTrials.gov Identifier: NCT02315118|
Recruitment Status : Unknown
Verified June 2016 by National University Hospital, Singapore.
Recruitment status was: Recruiting
First Posted : December 11, 2014
Last Update Posted : June 22, 2016
Despite advancement in chemotherapy, radiotherapy and haematopoietic stem cell transplant (HSCT), and the recent introduction of more targeted therapies, a substantial proportion of patients with B-cell malignancies, such as B-cell chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin's lymphoma (NHL) still succumb to their malignancies. For CLL and low-grade NHL, cure is achievable only with HSCT but such aggressive approach is not justified as the initial therapy for most patients who have indolent disease; when disease has progressed, transplant is either not feasible or ineffective. For high-grade B-cell NHL, the availability of Rituximab has improved disease outcome but treatment failure portends nearly inevitable death from disease or treatment-related complications. Thus, newer, more effective therapies for patients with B-cell malignancies are urgently needed.
The present study translates recent laboratory findings into clinical application. In patients with B-cell malignancies receiving the anti-CD20 antibody Rituximab as standard therapy, the study aims to assess the feasibility and safety, as well as explore the efficacy, of infusing autologous T-lymphocytes engineered to express a CD16-41BB-CD3zeta chimeric receptor which mediates antibody-dependent cell cytotoxicity. Receptor expression is achieved by electroporation of mRNA.
|Condition or disease||Intervention/treatment||Phase|
|B-Cell Chronic Lymphocytic Leukemia Non-Hodgkin's Lymphoma||Drug: T-cell therapy + Rituximab + IL-2||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of Autologous T Lymphocytes With Antibody-Dependent Cell Cytotoxicity in Patients With CD20-Positive B-Cell Malignancies|
|Study Start Date :||December 2014|
|Estimated Primary Completion Date :||December 2017|
|Estimated Study Completion Date :||December 2018|
Experimental: T-cell therapy + Rituximab + IL-2
Patients will undergo apheresis procedure and T cell expansion will be done in the laboratory. All patients will receive Rituximab on day -2 and IL-2 three times per week for one week starting on day -1 (dose 1 of 3). IL-2 dosing will be continued 3 times per week for one week (3 doses total).
On Day 0, T cell modification in the laboratory and T cell infusion in the patient will be done.
A disease status evaluation will be conducted approximately 4 weeks post-T cell infusion.
Drug: T-cell therapy + Rituximab + IL-2
Other Name: T-cell therapy
- Performance status assessed by age-dependent Performance Scores [ Time Frame: One-month (30 days) after the last T cell infusion ]Using KARNOFSKY PERFORMANCE STATUS SCALE (Recipient Age ≥ 16 years) and LANSKY PERFORMANCE STATUS SCALE (Recipient Age < 16 years)
- Toxicity criteria [ Time Frame: One-month (30 days) after the last T cell infusion ]
Participants will be monitored for toxicity for a period of one-month (30 days) after the last T cell infusion. Monitored toxicities will include the following:
- grades III-IV allergic reactions related to infusion;
- grade IV neutropenia lasting greater than 28 days;
- grade IV infection uncontrolled for greater than 7 days;
- grade IV other adverse events;
- treatment-related death (grade V).
- Disease response criteria [ Time Frame: One-month (30 days) after the last T cell infusion and at intervals thereafter till progression (approximately every 3 months for about a year) ]
Response criteria follow those defined by NCCN Guidelines version 4.2011 for CLL and NHL.
For monitoring of treatment response, patients with CLL and NHL will have PET-CT scan at approximately 1 month before and after infusion and at intervals thereafter till progression. Peripheral blood and bone marrow studies (the latter only if bone marrow is involved pre-treatment) will be done to determine levels of residual disease by using established flow cytometric and molecular MRD assays.
- Persistence of CD16+ T cells and impact on B cell function [ Time Frame: Up to approximately month ]
- The in vivo expression of anti-CD16V-BB-zeta on T cells will be monitored by flow cytometry. For this purpose, 10 ml of blood will be taken on Days 0, 1 and every other day after each infusion until infused T cells expressing the receptor become undetectable.
- Longer term impact on the suppression of B cell function will also be monitored by assaying B cell numbers and immunoglobulin levels.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02315118
|Contact: Michelle Poon, MBBS, MRCP||(65) 6779 5555|
|National University Hospital||Recruiting|
|Singapore, Singapore, 119228|
|Contact: Michelle Poon, MBBS, MRCP (65) 6779 5555|
|Principal Investigator: Michelle Poon, MBBS, MRCP|
|Principal Investigator: Yeh Ching Linn, MBBS, MRCP|
|Principal Investigator:||Michelle Poon, MBBS, MRCP||National University Hospital, Singapore|
|Principal Investigator:||Yeh Ching Linn, MBBS, MRCP||Singapore General Hospital|