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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2010-00416 | Registry Identifier | CTRP (Clinical Trial Reporting Program) |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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
PRIMARY OBJECTIVES:
I. 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:
I. 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (autologous CD20 specific T-cells) | Experimental | 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. 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| therapeutic autologous lymphocytes | Biological | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 2 years after final T cell infusion |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Up to 4 weeks after the third infusion |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Brian Till | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22308288 | Derived | 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. |
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| cyclophosphamide | Drug | Given IV |
|
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| aldesleukin | Biological | Given subcutaneously |
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| polymerase chain reaction | Genetic | Correlative studies |
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| gene rearrangement analysis | Genetic | Correlative studies |
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| lymph node biopsy | Procedure | Optional correlative studies |
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| genetically engineered lymphocyte therapy | Biological | Receive genetically modified T cells |
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| bone marrow aspiration | Procedure | Optional correlative studies |
|
| flow cytometry | Other | Correlative studies |
|
| laboratory biomarker analysis | Other | Correlative studies |
|
| enzyme-linked immunosorbent assay | Other | Correlative studies |
|
|
| 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. |
| Up to 12 months following treatment |
| Absolute numbers of T cells expressing the chimeric T Cell receptor (cTCR) per cubic uL of blood | Up to 1 year |
| ID | Term |
|---|---|
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D018442 | Lymphoma, B-Cell, Marginal Zone |
| D008224 | Lymphoma, Follicular |
| D020522 | Lymphoma, Mantle-Cell |
| D008258 | Waldenstrom Macroglobulinemia |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C082598 | aldesleukin |
| D007376 | Interleukin-2 |
| D016133 | Polymerase Chain Reaction |
| D015321 | Gene Rearrangement |
| D021701 | Sentinel Lymph Node Biopsy |
| D005434 | Flow Cytometry |
| D004797 | Enzyme-Linked Immunosorbent Assay |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D007378 | Interleukins |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D008222 | Lymphokines |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D021141 | Nucleic Acid Amplification Techniques |
| D005821 | Genetic Techniques |
| D008919 | Investigative Techniques |
| D055614 | Genetic Phenomena |
| D001706 | Biopsy |
| D003581 | Cytodiagnosis |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D013048 | Specimen Handling |
| D003949 | Diagnostic Techniques, Surgical |
| D013514 | Surgical Procedures, Operative |
| D008197 | Lymph Node Excision |
| D002469 | Cell Separation |
| D003592 | Cytophotometry |
| D005470 | Fluorometry |
| D008163 | Luminescent Measurements |
| D010783 | Photometry |
| D002623 | Chemistry Techniques, Analytical |
| D007124 | Immunoenzyme Techniques |
| D007118 | Immunoassay |
| D007158 | Immunologic Techniques |
| D007163 | Immunosorbent Techniques |
| D007150 | Immunohistochemistry |
| D015336 | Molecular Probe Techniques |
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