archive.org
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`DECLARATION OF NATHANIEL E FRANK-WHITE
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`1.
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`I am a Records Request Processor at the Internet Archive. I make this declaration
`of my own personal knowledge.
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`2. The Internet Archive is a website that provides access to a digital library of Internet
`sites and other cultural artifacts in digital form. Like a paper library, we provide
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`6. Attached hereto as Exhibit A are true and accurate copies of screenshots of the
`Internet Archive's records of the archived files for the URLs and the dates specified
`in the attached coversheet of each printout.
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`7. I declare under penalty of perjury that the foregoing is true and correct.
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`
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`DATE: ________________________
`
`
`________________________
`Nathaniel E Frank-White
`
`July 13, 2022
`
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`EXHIBIT A
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`EXHIBIT A
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`http://web.archive.org/web/20090903002304/http://clinicaltrials.gov/ct2/show/NCT00891215
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`INTERNET ARCHIVE_|http://clinicaltrials.gov/ct2/show/NCT00891215
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`
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`Wayoged(aching 6 captures
`7 May 2009- 28 Apr 2022
`@.10
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`ClinicalTrials.gov
`[Search
`Aservice of the U.S. National Institutes of Health
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`CULE Y Aboutthis capture
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`Study Topics Glossary
`Home
`Search
`
`
`
`
`Related Studies
`
`Full Text View
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`Tabular View
`
`No Study Results Posted
`
`Pilot Study for Patients With Chemotherapy Resistant or Refractory CD19 Leukemia and Lymphoma (CART-19)
`
`This study is currently recruiting participants.
`Verified by University of Pennsylvania, July 2009
`
`First Received: April 29, 2009 Last Updated: July 23, 2009 History of Changes
`
`Sponsors and Collaborators: University i Penfisylvania
`
`Lentigen Corporation
`
`® Purpose
`This is a study for people who have been previously treated for Leukemia/Lymphoma. In particular, it is a study for people who havea type of Leukemia/Lymphomathat involvesB cells (a type of
`white cell), which contain the cancer. This is a new approach for treatment of Leukemia/Lymphomathat involves B cells (tumorcells). This study will take the subject's white blood cells (T cells) and
`modify them in orderto target the cancer.
`
`The subject's T cells will be modified in one or two different waysthat will allow the cells to identify and kill the tumorcells (B cells). Both ways of modifying the cells tells the T cells to go to the B cells
`(tumorcells) and turn "on" and potentially kill the B cells (tumorcells). The modification is a genetic changeto theTcells, or gene transfer, in order to allow the modified T cells to recognize your
`tumorcells but not other normalcells in the subject's body. These modified cells are called CART-19 T cells.
`
`The two types of CART-19 T cells will be given back to subject's through aninfusion. In addition to determining the safety of this approach, the purposeof the study is to determine which way of
`modifying the T cells works betterin turning them "on"to fight cancer. This is done by monitoring levels of both types of modified cells in the subject's blood stream, andif possible, in the bone
`marrow and tumortissue for four weeks after the infusion. It is expected that one type of modified cell will grow better than the otherin the subject's blood. However,it is possible that there will be no
`difference betweenthe two typesofcells.
`
`Large Cell Lymphoma
`
`Acute Lymphocytic Leukemia
`Follicular Lymphoma
`Chronic Lymphocytic Leukemia (CLL)
`Mantle Cell Lymphoma
`Prolymphocytic Leukemia
`
`Biological: CART-19
`
`Interventional
`Study Type:
`Study Design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
`
`Official Title:
`
`Pilot Study of Redirected Autologous t Cells Engineered to Contain Anti-cd19 Attached to tcrg and 4-1bb Signaling Domains in Patients With Chemotherapy Resistant or Refractory
`cd19+ Leukemia and Lymphoma
`
`Resourcelinks provided by NLM:
`
`MedlinePlus related topics: Cancer Leukemia, AdultAcute Leukemia, Adult Chronic Lymphoma
`U.S. FDA Resources
`
`Further study details as provided by University of Pennsylvania:
`
`Primary Outcome Measures:
`¢ The changein the ratio of the vector transducedcells to each other between baseline and weekfourwill be evaluated. Observation and monitoring of patients will continue on a
`monthly basis until week 24 post dosing. [ Time Frame: 24 Weeks] [ Designated as safety issue: Yes ]
`
`Secondary Outcome Measures:
`¢ Subjects 6 to 10 will be dosed with mixtures of TCR:4-1BB and TCRonlycells, using a competitive repopulation strategy to determine the optimal signal transduction module in
`the chimeric receptor. [ Time Frame: 24 Weeks] [ Designated as safety issue: No ]
`
`Estimated Enrollment:
`Study Start Date:
`Estimated Study Completion Date:
`Estimated Primary Completion Date:
`
`10
`July 2009
`July 2010
`July 2010 (Final data collection date for primary outcome measure)
`
`Intervention Details:
`Biological: CART-19
`Total dose of CART-19 T Cells = ~2xE9 - 5xE10. CART-19 Cell infusion given over 3 days (Day 0, Day 1, Day 2) Eachinfusion is approximately 20 minutes. Asecond dose
`of CART-19 cells (~2.5 xE9 - 5 xE9Tcells) will be given administered byi.v. injection on day 11 to those patients who havesufficient CART-19 cells available.
`Detailed Description:
`
`This is an openlabel, single center, pilot study to evaluate the safety and tolerability, and differential persistence and engraftment of autologous T cells engineered to express a chimeric
`antigen receptor targeting CD19 whichislinked either to the CD3 or CD3:4-1BBsignaling chains in a competitive repopulation setting in patients with chemotherapy-resistantor-
`refractory CD19+ leukemia or lymphoma. Upon enrollment, patients will undergo leukapheresis (10L) and an optional bone marrow +/- lymph node biopsy approximately four weeks
`prior to dosing. T cells will be isolated from the leukapheresisbyelutriation, split and genetically modified in parallel by a lentiviral vector expressing one of the two chimeric antigen
`receptors, and then thecells will be expandedin parallel. Between dosing and treatment, patients may undergo an additional chemotherapy treatment depending upontheir disease. At
`dosing, patients will receive a mixture of the redirected autologousT cells against CD19 (CART-19 cells), which were producedin parallel. Twenty minutes after dosing, blood samples
`will be taken to serve as a baseline control for the ratio betweenthecells with either vector. Patients will be monitored weekly for four weeks. At the end of four weeks,patients will
`undergo a second leukapheresis (2L) and second optional bone marrow +/- lymph node biopsy. At this point the patient will also undergo restaging. The changein the ratio of the vector
`transducedcells to each other between baseline and weekfourwill be evaluated. Observation and monitoring of patients will continue on a monthly basis until week 24 post dosing. UPenn Ex. 2029
`Annualfollow-up for lentiviral vector safety will be carried out for 15 years in accordance with FDAguidelinesfor retroviral vectors. Ten subjects will be targeted for this study, with an
`.
`expectedrate of drop out of 30% dueto disease progression betweenenrollment and week four post dosing.
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`18 Years to 90 Years
`Both
`No
`
`®& Eligibility
`AgesEligible for Study:
`GendersEligible for Study:
`Accepts Healthy Volunteers:
`Criteria
`Inclusion Criteria:
`e CD19+ ACUTE LYMPHOBLASTIC LEUKEMIA(ALL). Must be in CR2 or CR3 and noteligible for allogeneic Stem Cell Transplant because of (age, comorbid disease,lack of related
`or unrelated donor)
`¢ CD19+ FOLLICULAR LYMPHOMA.Musthaveatleast 2 prior combination chemotherapy regimens(not including single agent monoclonal antibody (Rituxan) therapy. Must have
`StageIIl-IV disease. Less than 1 year between last chemotherapy and most current diagnosis of progression. Disease responding or stable after most recent therapy
`e CD19+ CHRONIC LYMPHOCYTIC LEUKEMIA (CLL). Musthaveat least 2 prior combination chemotherapy regimens(not including single agent monoclonal antibody (Rituxan)
`therapy.Less than 1 year between last chemotherapy and mostcurrent diagnosis of progression. Disease responding or stable after most recent therapy. Noteligible or appropriate
`for conventional allogeneic Stem Cell Transplant.
`¢ CD10+ MANTLE CELL LYMPHOMA.Beyond ‘st CR with relapsed or persistent disease. Noteligible or appropriate for conventional allogeneic or autologous SCT. Disease
`responding or stable after most recent therapy. Relapse after prior autologous Stem Cell Transplant.
`¢ CD19+ B-CELL PROLYMPHOCYTIC LEUKEMIA(PLL). Relapsed or residual disease after at least 1 prior therapy and noteligible for allogeneic Stem Cell Transplant.
`¢ CD19+ DIFFUSE LARGE CELL LYMPHOMA.Residual diseaseafter primary therapy. Noteligible for autologous Stem Cell Transplant. Relapsed after prior autologous Stem Cell
`Transplant. Beyond 1st CR with relapsed or persistent disease. Noteligible or appropriate for conventional or autologous Stem Cell Transplant.
`e Age greater or equal to 18 years of age.
`¢ Expected survival > 12 weeks.
`¢ Creatinine < 2.5 mg/dl.
`¢ ALT/AST< 3x normal.
`¢ Bilirubin < 2.0 mg/dl.
`¢ Any subject whorelapsesafter prior autologous Stem Cell Transplant will be eligible regardless of other prior therapy.
`e Adequate venousaccessfor apheresis and no other reasonsthat subject cannot undergo apheresis.
`¢ Able to give voluntary informed consent.
`Exclusion Criteria:
`e¢ Womenwhoare pregnantorlactating.
`¢ Subject has uncontrolled active infection.
`¢ Subject has HIV.
`¢ Subject has active Hepatitis B or Hepatitis C infection.
`¢ Subject uses systemic steroids (inhaled steroids are ok).
`¢ Subject has previously been given any gene therapy products.
`e Subject has any uncontrolled active medical disorder that would preclude participation in this study.
`
`® Contacts and Locations
`Pleaserefer to this studybyits ClinicalTrials.gov identifier: NCT00891215
`
`Contacts
`Contact: David Porter, MD trpctu@mail.med.upenn.edu
`
`Locations
`
`United States, Pennsylvania
`Recruiting
`University of Pennsylvania
`Philadelphia, Pennsylvania, United States, 19104
`
`Sponsors and Collaborators
`University of Pennsylvania
`Lentigen Corporation
`
`Investigators
`Principal Investigator: David Porter, MD University of Pennsylvania
`
`More Information
`
`Additional Information:
`
`Abramson CancerCenterClinical Trials Et)
`
`No publications provided
`
`University of Pennsylvania ( Dr. Carl H. June, Director, Translational Research Programs, Abramson Cancer Center, Professor of Pathology and Laboratory Medicine )
`Responsible Party:
`UPCC 04409
`Study ID Numbers:
`April 29, 2009
`Study First Received:
`July 23, 2009
`Last Updated:
`History of Changes
`ClinicalTrials.gov Identifier: NCT00891215
`Health Authority:
`United States: Food and Drug Administration
`
`Keywordsprovided by University of Pennsylvania:
`CD19+
`Leukemia
`Lymphoma
`
`Study placed in the following topic categories:
`Leukemia, Lymphoid
`Lymphoma,Large B-Cell, Diffuse
`Prolymphocytic Leukemia
`Precursor Cell Lymphoblastic Leukemia-Lymphoma
`Immunoproliferative Disorders
`Lymphoma,Mantle-Cell
`Lymphoma,Follicular
`Mantle Cell Lymphoma
`Follicular Lymphoma
`Lymphoma, B-Cell
`Leukemia
`
`Chronic Lymphocytic Leukemia
`Leukemia, Prolymphocytic
`B-cell Lymphomas
`Leukemia, Lymphocytic, Chronic, B-Cell
`Lymphoma,Large-cell
`Leukemia, B-cell, Chronic
`Lymphoma, Non-Hodgkin
`Leukemia, B-Cell
`Lymphoproliferative Disorders
`Lymphoma
`Acute Lymphoblastic Leukemia
`
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`Lymphatic Diseases
`Additional relevant MeSH terms:
`Leukemia, Lymphoid
`Lymphoma,Large B-Cell, Diffuse
`Immunoproliferative Disorders
`Precursor Cell Lymphoblastic Leukemia-Lymphoma
`NeoplasmsbyHistologic Type
`Immune System Diseases
`Lymphoma,Mantle-Cell
`Lymphoma,Follicular
`Lymphoma, B-Cell
`
`ClinicalTrials.gov processed this record on September 02, 2009
`
`Lymphatic Diseases
`Leukemia
`Neoplasms
`Leukemia, Prolymphocytic
`Leukemia, Lymphocytic, Chronic, B-Cell
`Lymphoma, Non-Hodgkin
`Leukemia, B-Cell
`Lymphoproliferative Disorders
`Lymphoma
`
`Contact Helo Desk
`Lister Hill National Center for Biomedical Communications, U.S. NationalLibrary of Medicine,
`U.S.NationalInstitutes of Health, U.S. Departmentof Health & Human Services,
`USA.gov, Copyright, Privacy, Accessibility, Freedom of Information Act
`wros,,
`a
`ty
`a
`owing
`Sens? INOUE
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`omy
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