Leukemia, Acute LymphoblasticPhase 2NCT02935543
CART19 in Adult Patients With Minimal Residual Disease During Upfront Treatment for ALL
A Phase 2 study testing CART 19 in people with Leukemia, Acute Lymphoblastic, run by University of Pennsylvania at 1 site in United States.
Trial summary
This is a single center, single arm, open-label phase 2 study to determine the efficacy of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART19" cells) in adults with minimal residual disease (MRD) during upfront… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Acute Lymphoblastic
- What is being tested?
- CART 19
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2016to 12 Dec 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with CD19+, B cell Acute Lymphoblastic Leukemia (B-ALL) who have 0.01%≤MRD<10% during upfront treatment
- Patients must be within 18 months of initial ALL diagnosis
- Age ≥18 years
- Adequate organ function defined as:
- Creatinine ≤ grade 2
- ALT/AST ≤3x upper limit of normal range for age
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- Direct bilirubin ≤2.0 mg/dl
- Adequate pulmonary function defined as ≤ grade 2 dyspnea and ≤ grade 2 hypoxia
- Cardiac Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
- Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy.
- Expression of CD19 on leukemic blasts demonstrated by flow cytometry or immunohistochemistry of bone marrow or peripheral blood
- Adequate performance status defined as ECOG Performance Status 0 or 1
- Provides written informed consent
- Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol
Who cannot join
- Active, uncontrolled infection
- Active hepatitis B or hepatitis C
- HIV Infection
- Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 2)
- Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of enrollment.
- Pregnant or nursing (lactating) women
- Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to leukemia or previous leukemia treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase 2 Study of CD19-directed Chimeric Antigen Receptor-modified T Cells (CART19) for Adult Patients With Minimal Residual Disease During Upfront Treatment for Acute Lymphoblastic Leukemia
This is a single center, single arm, open-label phase 2 study to determine the efficacy of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART19" cells) in adults with minimal residual disease (MRD) during upfront treatment for CD19+ acute lymphoblastic leukemia.
- Conditions
- Leukemia, Acute Lymphoblastic
- Being tested
- CART 19
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CART 19Biological
CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion. Subjects will receive 1-5 x 10^8 transduced CAR T cells as a split dose over three days as follows:Day 1, 10% fraction: 1-5x10^7 CART19 cells, Day 2, 30% fraction: 3x10^7-1.5x10^8 CART19 cells, Day 3, 60% fraction: 6x10^7-3x10^8 CART19 cells
| Study group | Role | What they receive |
|---|---|---|
| CART19 | Experimental | CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion. Receives: Biological: CART 19 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Incidence of Conversion of Minimal Residual Disease (MRD) to <0.01%
The incidence of conversion of minimal residual disease (MRD) to <0.01% after CART19 therapy in patients with MRD+ ALL during upfront treatment
Measured: Day 28
Secondary outcomes (6)
Best Overall Survival (OS)
Overall survival (OS) is defined as the time from the date of the first CART19 infusion to the date of death due to any reason.
Measured: one year
Duration of Remission (DOR)
Duration of remission (DOR) is defined as the duration from the date when the response criteria of CR or CRi is first met to the date of relapse or death due to ALL.
Measured: one year
Relapse Free Survival (RFS)
Relapse free survival (RFS) is defined as the duration between the date when the response criteria of CR or CRi is first met to the date of relapse or death due to any cause.
Measured: one year
Event Free Survival (EFS)
Event free survival (EFS) is defined as the time from start of the first CART19 infusion to the earliest of the following:
Death from any cause Relapse
Treatment failure: Defined as no response in the study and discontinuation from the study due to any of the following reasons:
- Adverse event(s)
- Abnormal laboratory value(s)
- Abnormal test procedure results
- New cancer therapy (excluding HSCT when performed in CR or CRi)
Measured: one year
Percentage of Manufacturing Products That do Not Meet Release Criteria for Vector Transduction Efficiency, T Cell Product Purity, Viability, Sterility or Due to Tumor Contamination.
Percentage of manufacturing products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility or due to tumor contamination.
Measured: prior to day 1
Safety and Tolerability of CART19: Frequency and Severity of Adverse Events, Including, But Not Limited to, Cytokine Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS).
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS) and macrophage activation syndrome (MAS).
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2016 (estimated)
- Study startOct 2016
- Primary completion12 Dec 2018
- Study completion12 Dec 2018
Why it stopped: Study is terminated because of administrative reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Leukemia, Acute LymphoblasticStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Noelle Frey, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02935543
- Sponsor's protocol ID
- UPCC39416, 825668
- Status last verified
- Jan 2020
- First submitted
- 12 Oct 2016
- Last updated
- 22 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of CD19-directed Chimeric Antigen Receptor-modified T Cells (CART19) for Adult Patients With Minimal Residual Disease During Upfront Treatment for Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT02935543
- Acronym / sponsor ID
- UPCC39416, 825668
- Conditions
- Leukemia, Acute Lymphoblastic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study is terminated because of administrative reasons.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Oct 2016 (actual)
- Primary completion
- 12 Dec 2018 (actual)
- Study completion
- 12 Dec 2018 (actual)
- First posted
- 17 Oct 2016 (estimated)
- Results
- Posted 5 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single center, single arm, open-label phase 2 study to determine the efficacy of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART19" cells) in adults with minimal residual disease (MRD) during upfront treatment for CD19+ acute lymphoblastic leukemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CART19 | Experimental | Biological: CART 19CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients with CD19+, B cell Acute Lymphoblastic Leukemia (B-ALL) who have 0.01%≤MRD<10% during upfront treatment
- Patients must be within 18 months of initial ALL diagnosis
- Age ≥18 years
- Adequate organ function defined as:
- Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy.
Key exclusion criteria (7 listed)
- Active, uncontrolled infection
- Active hepatitis B or hepatitis C
- HIV Infection
- Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 2)
- Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CART 19CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion. Subjects will receive 1-5 x 10^8 transduced CAR T cells as a split dose over three days as follows:Day 1, 10% fraction: 1-5x10^7 CART19 cells, Day 2, 30% fraction: 3x10^7-1.5x10^8 CART19 cells, Day 3, 60% fraction: 6x10^7-3x10^8 CART19 cells | Biological | CART19 |
Primary outcome
The Incidence of Conversion of Minimal Residual Disease (MRD) to <0.01%
Time frame: Day 28
The incidence of conversion of minimal residual disease (MRD) to <0.01% after CART19 therapy in patients with MRD+ ALL during upfront treatment
6 secondary outcomes
Best Overall Survival (OS)
Time frame: one year
Duration of Remission (DOR)
Time frame: one year
Relapse Free Survival (RFS)
Time frame: one year
Event Free Survival (EFS)
Time frame: one year
Percentage of Manufacturing Products That do Not Meet Release Criteria for Vector Transduction Efficiency, T Cell Product Purity, Viability, Sterility or Due to Tumor Contamination.
Time frame: prior to day 1
Safety and Tolerability of CART19: Frequency and Severity of Adverse Events, Including, But Not Limited to, Cytokine Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS).
Time frame: one year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Noelle Frey, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CART 19 in people with Leukemia, Acute Lymphoblastic, run by University of Pennsylvania 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 14 inclusion and 7 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: stopped early, as of the sponsor's last update on 22 Jun 2023. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Incidence of Conversion of Minimal Residual Disease (MRD) to <0.01% (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Jun 2023.