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B-Cell Chronic Lymphocytic LeukemiaPhase 1/2NCT02315118

Pilot Study of Autologous T Lymphocytes With ADCC in Patients With CD20-Positive B-Cell Malignancies

A Phase 1/2 study testing T-cell therapy + Rituximab + IL-2 in people with B-Cell Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma, run by National University Hospital, Singapore at 1 site in Singapore.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 6 months to 80 years
What is being tested?
T-cell therapy + Rituximab + IL-2
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteSingapore
Study dates
Dec 2014to Dec 2018
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 80 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age: 6 months to 80 years old.
  • i) Diagnosis of aggressive CD20+ B-NHL with measurable tumor burden (by imaging, flow cytometry and/or PCR) post-treatment. This includes patients with persistent disease following more than 2 lines of chemotherapy, as well as patients who relapse following autologous transplantation, and in whom further salvage therapy has produced only a partial remission or where no effective salvage therapy available. Patients with bulky disease who require immediate salvage therapy will not be eligible.
  • OR ii) Diagnosis of poor risk indolent CD20+ B-NHL or Chronic Lymphocytic Leukemia. This includes high risk CLL cases with early relapse (<12 months following purine analog containing treatment or <24 months following autologous transplant), or with 17p deletion needing treatment, and who are not candidates (or refuses) allogeneic transplantation. Patients with advanced progressive indolent B-NHL with relapsed, refractory disease who have failed more than 2 lines of treatment (including autologous transplantation) may also be considered.
  • Shortening fraction greater than or equal to 25%.
  • Glomerular filtration rate greater than or equal to 50 ml/min/1.73 m2.
  • Pulse oximetry greater than or equal to 92% on room air.
Show all 16Show fewer
  • Direct bilirubin less than or equal to 3.0 mg/dL (50 mmol/L).
  • Alanine aminotransferase (ALT) is no more than 2 times the upper limit of normal unless determined to be directly due to disease.
  • Aspartate transaminases (AST) is no more than 2 times the upper limit of normal unless determined to be directly due to disease.
  • Karnofsky or Lansky performance score of greater than or equal to 50.
  • No clinical history of or overt autoimmune disease.
  • No past history of previous severe adverse reactions to rituximab, eg. cytokine release syndrome
  • Has recovered from all acute NCI Common Toxicity Criteria grade II-IV non-hematologic acute toxicities resulting from prior therapy per the judgment of the PI.
  • Is not receiving more than the equivalent of prednisone 10 mg daily.
  • Not pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
  • Not lactating.

Who cannot join

  • Failure to meet any of the inclusion criteria

Trial locations and contacts

1 site in 1 country.

Michelle Poon, MBBS, MRCP contact

(65) 6779 5555

Singapore1 site, 1 recruiting

  • National University Hospital

    Singapore, Singapore, 119228

    Michelle Poon, MBBS, MRCP, (65) 6779 5555

    Michelle Poon, MBBS, MRCP

    Recruiting

Other trials in Singapore

About this study

Official title: Pilot Study of Autologous T Lymphocytes With Antibody-Dependent Cell Cytotoxicity in Patients With CD20-Positive B-Cell Malignancies

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.

Being tested
T-cell therapy + Rituximab + IL-2
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • T-cell therapy + Rituximab + IL-2Drug

    Also called T-cell therapy

    • T cells collection
    • T cells expansion and modification in the laboratory
    • T cells infusion back to the patients
Study groups in NCT02315118
Study groupRoleWhat they receive
T-cell therapy + Rituximab + IL-2ExperimentalPatients 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.
Receives: Drug: T-cell therapy + Rituximab + IL-2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Performance status assessed by age-dependent Performance Scores

    Using KARNOFSKY PERFORMANCE STATUS SCALE (Recipient Age ≥ 16 years) and LANSKY PERFORMANCE STATUS SCALE (Recipient Age < 16 years)

    Measured: One-month (30 days) after the last T cell infusion

  2. Toxicity criteria

    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:

    1. grades III-IV allergic reactions related to infusion;
    2. grade IV neutropenia lasting greater than 28 days;
    3. grade IV infection uncontrolled for greater than 7 days;
    4. grade IV other adverse events;
    5. treatment-related death (grade V).

    Measured: One-month (30 days) after the last T cell infusion

  3. Disease response criteria

    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.

    Measured: One-month (30 days) after the last T cell infusion and at intervals thereafter till progression (approximately every 3 months for about a year)

  4. Persistence of CD16+ T cells and impact on B cell function

    1. 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.
    2. Longer term impact on the suppression of B cell function will also be monitored by assaying B cell numbers and immunoglobulin levels.

    Measured: Up to approximately month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2014 (estimated)
  2. Study startDec 2014
  3. Primary completionDec 2017 (estimated)
  4. Study completionDec 2018 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02315118
Sponsor's protocol ID
2014/00584
Other IDs
2014
Status last verified
Jun 2016
First submitted
27 Nov 2014
Last updated
22 Jun 2016
Results posted
No
Data monitoring committee
No

Publications

  • Kudo K, Imai C, Lorenzini P, Kamiya T, Kono K, Davidoff AM, Chng WJ, Campana D. T lymphocytes expressing a CD16 signaling receptor exert antibody-dependent cancer cell killing. Cancer Res. 2014 Jan 1;74(1):93-103. doi: 10.1158/0008-5472.CAN-13-1365. Epub 2013 Nov 6.

    PubMed 24197131

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing T-cell therapy + Rituximab + IL-2 in people with B-Cell Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma, run by National University Hospital, Singapore at 1 site in Singapore.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 22 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Michelle Poon, MBBS, MRCP ((65) 6779 5555), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Performance status assessed by age-dependent Performance Scores (time frame: One-month (30 days) after the last T cell infusion). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02315118, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2016.

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