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B-cell Chronic Lymphocytic LeukemiaPhase 1NCT00621452

Genetically Engineered Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Indolent B-Cell Non-Hodgkin Lymphoma

A Phase 1 study testing therapeutic autologous lymphocytes, cyclophosphamide and aldesleukin in people with B-cell Chronic Lymphocytic Leukemia and Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, run by Fred Hutchinson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial is studying the side effects of giving genetically engineered lymphocytes together with cyclophosphamide and aldesleukin in treating patients with relapsed or refractory mantle cell lymphoma or indolent B-cell non-Hodgkin lymphoma. Read more about this study

Who is it for?
Any age
What is being tested?
therapeutic autologous lymphocytes, cyclophosphamide and aldesleukin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
Aug 2007to Jan 2014
Phase
Phase 1
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Male or female subjects with immuno histopathologically documented CD20+ mantle cell lymphoma, follicular non-Hodgkin lymphoma (NHL), small lymphocytic lymphoma/chronic lymphocytic leukemia, marginal zone, or lymphoplasmacytic NHL of any age, gender, or ethnic group who have relapsed or are refractory to conventional chemotherapy and who are not eligible for Fred Hutchinson Cancer Research Center (FHCRC)/University of Washington Medical Center (UWMC) transplant protocols (or who refuse participation in transplant protocols)
  • Willingness to sign an informed consent and undergo study tests
  • Willingness to receive cytoreductive chemotherapy, if necessary to debulk tumors prior to T cell administration, and to receive cyclophosphamide for lymphodepletion
  • Serologic evidence of prior exposure to Epstein-Barr virus (EBV)
  • Meets safety criteria to undergo leukapheresis
  • Hemoglobin > 9.0 gm/dL
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  • White blood cell (WBC) > 2500 per microliter
  • Alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x Upper Limit of Normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x Upper Limit of Normal
  • Creatinine =< 1.6 mg/dL
  • Willingness to use acceptable (barrier or hormonal methods) birth control as appropriate during the course of the study

Who cannot join

  • Treatment with fludarabine or cladribine within the previous 2 years prior to apheresis
  • Known central nervous system involvement with NHL
  • Pulmonary involvement with NHL; a diagnosis of pulmonary lymphoma will be based in part on findings from chest computed tomography (CT) and, if clinically appropriate, lung biopsy
  • Exposure to chemotherapeutic agents (standard or experimental) or other immunosuppressive therapies less than four weeks prior to apheresis; patients must have recovered from acute side effects of such therapy
  • Positive serology for human immunodeficiency virus (HIV)
  • Active Hepatitis B or Hepatitis C infection
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  • History of hypersensitivity reactions to murine proteins or seropositivity for human anti-mouse antibody (HAMA)
  • Requirement for corticosteroid therapy during the study period unless used specifically for amelioration of toxicity induced by transferred cells
  • Treatment with anti-CD20 antibodies (rituximab, tositumomab, ibritumomab) within 4 months prior to start of T cell infusions
  • Patients with lymph nodes in excess of 5 cm in diameter at time of T cell infusion
  • Patients with > 5000 circulating CD20+ lymphocytes per mm^3 at time of T cell infusion
  • Previous allogeneic stem cell transplantation
  • Life expectancy less than 90 days
  • Pregnancy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Pilot Study to Evaluate the Safety and Feasibility of Cellular Immunotherapy Using Genetically Modified Autologous CD20-Specific T Cells For Patients With Relapsed or Refractory Mantle Cell and Indolent B Cell Lymphomas

This phase I trial is studying the side effects of giving genetically engineered lymphocytes together with cyclophosphamide and aldesleukin in treating patients with relapsed or refractory mantle cell lymphoma or indolent B-cell non-Hodgkin lymphoma. Placing a gene that has been created in the laboratory into white blood cells may make the body build an immune response to kill cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Aldesleukin may stimulate the white blood cells to kill lymphoma cells. Giving genetically engineered lymphocytes together with cyclophosphamide and aldesleukin may be an effective treatment for mantle cell lymphoma and B-cell non-Hodgkin lymphoma

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the feasibility, safety and toxicity of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express a "second generation' cluster of differentiation (CD)20-specific scFvFc:CD28:CD137:zeda chimeric immunoreceptor in patients with recurrent or refractory CD20+ mantle cell or indolent lymphoma.

SECONDARY OBJECTIVES:

  1. To determine the duration of in vivo persistence of adoptively transferred CD20-specific T cells transfected with a CD20-specific scFvFc:CD28:CD137:zeda chimeric immunoreceptor.

II. To assess the trafficking of CD20-specific T cells to lymphoma masses. III. To evaluate the development of host anti-CD20 scFvFc:CD28:CD137:zeda chimeric immunoreceptor and anti-neomycin-resistance gene (NeoR) immune responses in study subjects.

OUTLINE:

CHEMOTHERAPY: Patients receive cyclophosphamide IV over 60 minutes.

IMMUNOTHERAPY: Beginning 2 days after completion of cyclophosphamide, patients receive autologous CD20-specific T-cells IV over 30 minutes. Treatment repeats every 2-5 days for 3 courses.

MAINTENANCE THERAPY: Beginning 2 hours after the last T-cell infusion, patients receive low-dose aldesleukin subcutaneously twice daily for 14 days.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Subjects who have achieved at least a partial remission lasting a minimum of 6 months may, on a case-by-case basis, receive additional stored T cells following relapse.

After completion of study treatment, patients are followed up weekly for one month, monthly for 1 year, and then annually for up to 2 years.

Being tested
therapeutic autologous lymphocytes, cyclophosphamide, aldesleukin, polymerase chain reaction, gene rearrangement analysis
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Waldenstrom Macroglobulinemia

What participants receive

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

  • therapeutic autologous lymphocytesBiological

    Also called AL, Autologous Lymphocytes, autologous T cells

    Given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • aldesleukinBiological

    Also called IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

    Given subcutaneously

  • polymerase chain reactionGenetic

    Also called PCR

    Correlative studies

  • gene rearrangement analysisGenetic

    Correlative studies

  • lymph node biopsyProcedure or surgery

    Also called Biopsy of Lymph Node

    Optional correlative studies

  • genetically engineered lymphocyte therapyBiological

    Receive genetically modified T cells

  • bone marrow aspirationProcedure or surgery

    Optional correlative studies

  • flow cytometryOther

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

  • enzyme-linked immunosorbent assayOther

    Also called ELISA

    Correlative studies

Study groups in NCT00621452
Study groupRoleWhat they receive
Treatment (autologous CD20 specific T-cells)ExperimentalCHEMOTHERAPY: Patients receive cyclophosphamide IV over 60 minutes. IMMUNOTHERAPY: Beginning 2 days after completion of cyclophosphamide, patients receive autologous CD20-specific T-cells IV over 30 minutes. Treatment repeats every 2-5 days for 3 courses. MAINTENANCE THERAPY: Beginning 2 hours after the last T-cell infusion, patients receive low-dose aldesleukin subcutaneously twice daily for 14 days. Subjects who have achieved at least a partial remission lasting a minimum of 6 months may, on a case-by-case basis, receive additional stored T cells following relapse.
Receives: Biological: therapeutic autologous lymphocytes; Drug: cyclophosphamide; Biological: aldesleukin; Genetic: polymerase chain reaction; Genetic: gene rearrangement analysis; Procedure: lymph node biopsy; Biological: genetically engineered lymphocyte therapy; Procedure: bone marrow aspiration; Other: flow cytometry; Other: laboratory biomarker analysis; Other: enzyme-linked immunosorbent assay

What is being measured

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

  1. Feasibility of transfecting and expanding the necessary numbers of T cells and the types of problems and toxicities which might be encountered, graded according the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0

    A true grade 3 or higher toxicity rate in excess of 20% attributed to T cell infusions will be considered grounds for stopping the study and amending the protocol to lower the cell infusion doses. If there ever exists sufficient evidence to suggest that the true T cell-related toxicity rate (grade 3 or higher, with the exception of fever > 40 degrees Celsius lasting less than 24 hours) exceeds 20%, the study will be stopped.

    Measured: Up to 2 years after final T cell infusion

Secondary outcomes (3)

  1. Comparison of the percentages of CD20-specific T cells and malignant B cells present in the blood before and after each T cell infusion

    Numbers and percentages of CD20-specific T cells and of malignant B cells will also be quantified in lymph node (LN) and bone marrow (BM).

    Measured: Up to 4 weeks after the third infusion

  2. Immune response as assessed by ELISA and percent chromium release in cytotoxicity assays

    Means, medians and standard deviation (S.D.) of the Ab titers observed will be computed.

    Measured: Up to 12 months following treatment

  3. Absolute numbers of T cells expressing the chimeric T Cell receptor (cTCR) per cubic uL of blood

    Measured: Up to 1 year

Timeline

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

  1. First posted22 Feb 2008 (estimated)
  2. Study startAug 2007
  3. Primary completionJan 2014

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00621452
Sponsor's protocol ID
2154.00
Other IDs
NCI-2010-00416
Status last verified
Aug 2014
First submitted
21 Feb 2008
Last updated
6 Aug 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Till BG, Jensen MC, Wang J, Qian X, Gopal AK, Maloney DG, Lindgren CG, Lin Y, Pagel JM, Budde LE, Raubitschek A, Forman SJ, Greenberg PD, Riddell SR, Press OW. CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results. Blood. 2012 Apr 26;119(17):3940-50. doi: 10.1182/blood-2011-10-387969. Epub 2012 Feb 3.

    PubMed 22308288

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing therapeutic autologous lymphocytes, cyclophosphamide and aldesleukin in people with B-cell Chronic Lymphocytic Leukemia and Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, run by Fred Hutchinson Cancer Center at 1 site in United States.

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 11 inclusion and 14 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: finished, as of the sponsor's last update on 6 Aug 2014. 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 United States. 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 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.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasibility of transfecting and expanding the necessary numbers of T cells and the types of problems and toxicities which might be encountered, graded according the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (time frame: Up to 2 years after final T cell infusion). 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 NCT00621452, 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 6 Aug 2014.

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