Pilot Study of Autologous T Lymphocytes With ADCC in Patients With CD20-Positive B-Cell Malignancies
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|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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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|