CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy
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
2 other identifiers
interventional
26
1 country
1
Brief Summary
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: 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Mar 2010
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 9, 2009
CompletedFirst Posted
Study publicly available on registry
December 10, 2009
CompletedStudy Start
First participant enrolled
March 17, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2016
CompletedResults Posted
Study results publicly available
February 28, 2017
CompletedJune 22, 2023
June 1, 2019
5.3 years
December 9, 2009
June 28, 2016
June 20, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants With Adverse Events
5 years
Secondary Outcomes (1)
Overall Response Summary
5 years
Study Arms (2)
CART-19 CLL
EXPERIMENTALCART-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).
CART-19 ALL
EXPERIMENTALCART-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).
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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
- 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
- +14 more criteria
You may not qualify if:
- 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
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Abramson Cancer Center of The University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Related Publications (3)
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.
PMID: 31815579DERIVEDvan 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.
PMID: 31076448DERIVEDMaude 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.
PMID: 25317870DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Noelle Frey, MD
- Organization
- Abramson Cancer Center of the University of Pennsylvania
Study Officials
- PRINCIPAL INVESTIGATOR
Noelle Frey, MD
Abramson Cancer Center at Penn Medicine
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 9, 2009
First Posted
December 10, 2009
Study Start
March 17, 2010
Primary Completion
July 1, 2015
Study Completion
May 1, 2016
Last Updated
June 22, 2023
Results First Posted
February 28, 2017
Record last verified: 2019-06