CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy - Full Text View - ClinicalTrials.gov
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`CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to
`Chemotherapy
`
`
`
`ClinicalTrials.gov Identifier: NCT01029366
`
`Recruitment Status  : Completed
`First Posted  : December 10, 2009
`Results First Posted  : February 28, 2017
`Last Update Posted  : June 26, 2019
`
`A
`
`The safety and scientific validity of
`this study is the responsibility of the
`study sponsor and investigators.
`Listing a study does not mean it has
`been evaluated by the U.S. Federal
`Government. Read our disclaimer
`for details.
`
`Sponsor:
`University of Pennsylvania
`
`Information provided by (Responsible Party):
`University of Pennsylvania
`
`-
`
`Study Details
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`Study Results
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`Study Description
`
`Brief Summary:
`
`Go to
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`...
`
`This is a Pilot/Phase I, single arm, single center, open label study to determine the safety, efficacy and cellular
`kinetics of CART19 (CTL019) in chemotherapy resistant or refractory CD19+ leukemia and lymphoma subjects.
`The study consists of three Phases:
`
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`CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy - Full Text View - ClinicalTrials.gov
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`1) a Screening Phase, followed by 2) an Intervention/Treatment Phase consisting of apheresis,
`lymphodepleting chemotherapy (determined by the Investigator and based on subject's disease burden and
`histology, as well as on the prior chemotherapy history received), infusions of CTL019, tumor collection by bone
`marrow aspiration or lymph node biopsy (optional, depending on availability), and 3) a Follow-up Phase.
`
`The suitability of subjects' T cells for CTL019 manufacturing was determined at study entry.
`
`Subjects with adequate T cells were leukapheresed to obtain large numbers of peripheral blood mononuclear
`cells for CTL019 manufacturing. The T cells were purified from the peripheral blood mononuclear cells,
`transduced with TCR-ζ/4-1BB lentiviral vector, expanded in vitro and then frozen for future administration. The
`number of subjects who had inadequate T cell collections, expansion or manufacturing compared to the
`number of subjects who had T cells successfully manufactured is a primary measure of feasibility of this study.
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`Unless contraindicated and medically not advisable based on previous chemotherapy, subjects were given
`conditioning chemotherapy prior to CTL019 infusion. The chemotherapy was completed 1 to 4 days before the
`planned infusion of the first dose of CTL019.
`
`Up to 20 evaluable subjects with CD19+ leukemia or lymphoma were planned to be dosed with CTL019. A
`single dose of CTL019 (consisting of approximately 5x10^9 total cells, with a minimal acceptable dose for
`infusion of 1.5x10^7 CTL019 cells) was to be given to subjects as fractions (10%, 30% and 60% of the total
`dose) on Day 0, 1 and 2. A second 100% dose of CTL019 was initially permitted to be given on Day 11 to 14 to
`subjects, providing they had adequate tolerance to the first dose and sufficient CTL019 was manufactured.
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`Intervention/treatment 
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`Phase 
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`Biological: CART-19
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`Phase 1
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`Condition or disease 
`
`Hematopoietic/Lymphoid Cancer
`Adult Acute Lymphoblastic Leukemia in Remission
`B-cell Adult Acute Lymphoblastic Leukemia
`B-cell Chronic Lymphocytic Leukemia
`Prolymphocytic Leukemia
`Recurrent Adult Diffuse Large Cell Lymphoma
`Recurrent Grade 1 Follicular Lymphoma
`Recurrent Grade 2 Follicular Lymphoma
`Recurrent Grade 3 Follicular Lymphoma
`Recurrent Mantle Cell Lymphoma
`Refractory Chronic Lymphocytic Leukemia
`Stage III Adult Diffuse Large Cell Lymphoma
`Stage III Chronic Lymphocytic Leukemia
`Stage III Grade 1 Follicular Lymphoma
`Stage III Grade 2 Follicular Lymphoma
`Stage III Grade 3 Follicular Lymphoma
`
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`CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy - Full Text View - ClinicalTrials.gov
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`Stage III Mantle Cell Lymphoma
`Stage IV Adult Diffuse Large Cell Lymphoma
`Stage IV Chronic Lymphocytic Leukemia
`Stage IV Grade 1 Follicular Lymphoma
`Stage IV Grade 2 Follicular Lymphoma
`Stage IV Grade 3 Follicular Lymphoma
`Stage IV Mantle Cell Lymphoma
`
`Detailed Description:
`
`Primary objectives:
`
`1. To evaluate the safety and feasibility of a single target dose of 5 times 10e9 total cells, acceptable range of
`1.5 times 10e7 to 5 times 10e9 total cells comprised of autologous CART-19 cells that express the TCR zeta
`and 4-1 BB costimulatory domain.
`
`Secondary objectives:
`
`1. Proof of mechanism: determine if 2nd generation CAR expressing 4-1BB costimulation domains have
`improved persistence in patients.
`2. Proof of concept: determine the effects of CART-19 on CD19 expression in vivo.
`3. Proof of bioactivity: Evaluate changes in systemic soluble immune factors in patients
`4. Proof of bioactivity: Evaluate impact of CART19 treatment on tumor burden
`5. Explore whether CART-19 cells retain anti-tumor activity in vivo.
`6. Determine if host immunity develops against CART-19.
`7. Characterize the relative subsets of CART-19 T cells (Tcm, Tem, and Treg).
`8. Describe survival and response rates
`
`Study Design
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`Go to
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`Interventional (Clinical Trial)
`Study Type  :
`Actual Enrollment  : 26 participants
`Allocation: Non-Randomized
`Intervention Model: Single Group Assignment
`Masking: None (Open Label)
`Primary Purpose: Treatment
`Official Title: Pilot Study of Redirected Autologous T-cells Engineered to Contain Anti-
`CD19 Attached to TCR and 4-1BB Signaling Domains in Patient With
`Chemotherapy Resistant or Refractory CD19+ Leukemia and Lymphoma
`Actual Study Start Date  : March 17, 2010
`Actual Primary Completion Date  : July 2015
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`CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy - Full Text View - ClinicalTrials.gov
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`Actual Study Completion Date  : May 2016
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`Resource links provided by the National Library of Medicine
`
`llll)NLM
`
`MedlinePlus related topics: Leukemia Lymphoma
`
`Drug Information available for: Tisagenlecleucel-T
`
`Genetic and Rare Diseases Information Center resources: Lymphosarcoma
`Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Diffuse Large B-
`Cell Lymphoma Chronic Lymphocytic Leukemia Mantle Cell Lymphoma
`Follicular Lymphoma B-cell Lymphoma
`
`U.S. FDA Resources
`
`Arms and Interventions
`
`Go to
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`Arm 
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`Intervention/treatment 
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`Experimental: CART-19 CLL
`CART-19 (autologous T cells transduced with
`CD19 TCR-ζ/4-1BB vector) administered as an IV
`infusion days 0, 1, 2 and 11 in the absence of
`disease progression or unacceptable
`toxicity.Minimum/maximum total dose: 1.5x10^7 /
`5x10^9 administered to patients with chronic
`Lymphocytic Leukemia (CLL) and Acute
`Lymphoblastic Leukemia (ALL).
`
`Experimental: CART-19 ALL
`CART-19 (autologous T cells transduced with
`CD19 TCR-ζ/4-1BB vector) administered as an IV
`infusion days 0, 1, 2 and 11 in the absence of
`disease progression or unacceptable
`toxicity.Minimum/maximum total dose: 1.5x10^7 /
`5x10^9 administered to patients with chronic
`Lymphocytic Leukemia (CLL) and Acute
`Lymphoblastic Leukemia (ALL).
`
`Biological: CART-19
`Autologous T cells purified from the peripheral
`blood mononuclear cells of subjects, transduced
`with TCR-ζ/4-1BB lentiviral vector, expanded in
`vitro and then frozen for future administration.
`
`Biological: CART-19
`Autologous T cells purified from the peripheral
`blood mononuclear cells of subjects, transduced
`with TCR-ζ/4-1BB lentiviral vector, expanded in
`vitro and then frozen for future administration.
`
`Outcome Measures
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`Go to
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`https://clinicaltrials.gov/ct2/show/NCT01029366[4/5/2022 1:47:36 PM]
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`CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy - Full Text View - ClinicalTrials.gov
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`Primary Outcome Measures  :
`1. Number of Participants With Adverse Events [ Time Frame: 5 years ]
`
`Secondary Outcome Measures  :
`1. Overall Response Summary [ Time Frame: 5 years ]
`
`Efficacy assessments for ALL were performed based on bone marrow and blood morphologic criteria
`and physical examination findings. The definitions for response are primarily based on the standardized
`response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN,
`2013 v.1).
`
`Efficacy assessments for CLL were based on lymphadenopathy, hepatomegaly, splenomegaly, bone
`marrow and blood morphologic and laboratory assessments. The response criteria are consistent with
`NCCN Guidelines Version 2.2012 CLL/SLL, which is based on the 2008 International Workshop Group
`on CLL (IWCLL) revisions of the original guidelines for evaluating disease response released in 1996
`by the National Cancer Institute Working Group (NCI/WG).
`
`Eligibility Criteria
`
`Go to
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`...
`
`Information from the National Library of Medicine
`
`llll}NLM
`Choosing to participate in a study is an important personal decision. Talk with your
`doctor and family members or friends about deciding to join a study. To learn more
`about this study, you or your doctor may contact the study research staff using the
`contacts provided below. For general information, Learn About Clinical Studies.
`
`Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
`Sexes Eligible for Study: All
`Accepts Healthy Volunteers: No
`
`Criteria
`Inclusion
`•
`
`Male and female subjects with CD19+ B cell malignancies in patients with no available curative treatment
`options (such as autologous or allogeneic SCT) who have limited prognosis (several months to < 2 year
`survival) with currently available therapies will be enrolled
`
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`CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy - Full Text View - ClinicalTrials.gov
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`CD19+ leukemia or lymphoma
`ALL in CR2 or CR3 and not eligible for allogeneic SCT because of age, comorbid disease, or lack of
`available family member or unrelated donor
`Follicular lymphoma, previously identified as CD19+:
`At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody
`(Rituxan) therapy
`Stage III-IV disease
`Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1
`year)
`Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc)
`CLL:
`At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy.
`Patients with high risk disease manifested by deletion chromosome 17p will be eligible if they fail to achieve
`a CR to initial therapy or progress within 2 years of 1 prior
`Less than 2 years between last chemotherapy and progression (i.e. most recent progression free interval <
`2 years)
`Not eligible or appropriate for conventional allogeneic SCT
`Patients who achieve only a partial response to FCR as initial therapy will be eligible.
`Mantle cell lymphoma:
`Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional
`allogeneic or autologous SCT
`Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc...)
`Relapsed after prior autologous SCT
`B-cell prolymphocytic leukemia (PLL) with relapsed or residual disease after at least 1 prior therapy and not
`eligible for allogeneic SCT
`Diffuse large cell lymphoma, previously identified as CD19+:
`Residual disease after primary therapy and not eligible for autologous SCT
`Relapsed after prior autologous SCT
`Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate of conventional
`allogeneic or autologous SCT
`Expected survival > 12 weeks
`Creatinine < 2.5 mg/dl
`ALT/AST < 3x normal
`Bilirubin < 2.0 mg/dl
`Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy
`
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`CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy - Full Text View - ClinicalTrials.gov
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`Adequate venous access for apheresis, and no other contraindications for leukapheresis
`Voluntary informed consent is given
`
`•
`•
`Exclusion
`•
`•
`•
`
`Pregnant or lactating women
`The safety of this therapy on unborn children is not known
`Female study participants of reproductive potential must have a negative serum or urine pregnancy test
`performed within 48 hours before infusion
`Uncontrolled active infection
`Active hepatitis B or hepatitis C infection
`Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
`Previously treatment with any gene therapy products
`Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or
`insufficient expansion (< 5-fold) in response to CD3/CD28 costimulation
`Any uncontrolled active medical disorder that would preclude participation as outlined
`HIV infection
`
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`Contacts and Locations
`
`Go to
`
`Information from the National Library of Medicine
`
`llll)NLM
`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):
`NCT01029366
`
`Locations
`
`United States, Pennsylvania
`Abramson Cancer Center of The University of Pennsylvania
`Philadelphia, Pennsylvania, United States, 19104
`
`Sponsors and Collaborators
`University of Pennsylvania
`
`Investigators
`
`https://clinicaltrials.gov/ct2/show/NCT01029366[4/5/2022 1:47:36 PM]
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`CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy - Full Text View - ClinicalTrials.gov
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`Principal Investigator: Noelle Frey, MD Abramson Cancer Center of the University of Pennsylvania
`
`More Information
`
`Go to
`
`Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
`
`Frey NV, Shaw PA, Hexner EO, Pequignot E, Gill S, Luger SM, Mangan JK, Loren AW, Perl AE, Maude SL,
`Grupp SA, Shah NN, Gilmore J, Lacey SF, Melenhorst JJ, Levine BL, June CH, Porter DL. Optimizing Chimeric
`Antigen Receptor T-Cell Therapy for Adults With Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Feb
`10;38(5):415-422. doi: 10.1200/JCO.19.01892. Epub 2019 Dec 9.
`
`van Bruggen JAC, Martens AWJ, Fraietta JA, Hofland T, Tonino SH, Eldering E, Levin MD, Siska PJ, Endstra
`S, Rathmell JC, June CH, Porter DL, Melenhorst JJ, Kater AP, van der Windt GJW. Chronic lymphocytic
`leukemia cells impair mitochondrial fitness in CD8(+) T cells and impede CAR T-cell efficacy. Blood. 2019 Jul
`4;134(1):44-58. doi: 10.1182/blood.2018885863. Epub 2019 May 10.
`
`Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF,
`Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA.
`Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct
`16;371(16):1507-17. doi: 10.1056/NEJMoa1407222. Erratum in: N Engl J Med. 2016 Mar 10;374(10):998.
`
`University of Pennsylvania
`Responsible Party:
`ClinicalTrials.gov Identifier: NCT01029366 History of Changes
`Obsolete Identifiers:
`NCT00891215
`Other Study ID Numbers:
`UPCC04409, 809517
`NCI-2009-01357
`December 10, 2009 Key Record Dates
`February 28, 2017
`June 26, 2019
`June 2019
`
`First Posted:
`Results First Posted:
`Last Update Posted:
`Last Verified:
`
`Additional relevant MeSH terms:
`Lymphoma
`Leukemia
`Lymphoma, Follicular
`Leukemia, Lymphoid
`Precursor Cell Lymphoblastic Leukemia-Lymphoma
`Lymphoma, Non-Hodgkin
`Leukemia, Lymphocytic, Chronic, B-Cell
`Lymphoma, Mantle-Cell
`Lymphoma, Large B-Cell, Diffuse
`
`https://clinicaltrials.gov/ct2/show/NCT01029366[4/5/2022 1:47:36 PM]
`
`Leukemia, Prolymphocytic
`Neoplasms by Histologic Type
`Neoplasms
`Lymphoproliferative Disorders
`Lymphatic Diseases
`Immunoproliferative Disorders
`Immune System Diseases
`Leukemia, B-Cell
`Lymphoma, B-Cell
`
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`CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy - Full Text View - ClinicalTrials.gov
`
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`https://clinicaltrials.gov/ct2/show/NCT01029366[4/5/2022 1:47:36 PM]
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