Patients With B Cell ALL, Relapsed or Refractory, With no Available Curative Treatment OptionsPhase 2NCT02030847
Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCR and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant or Refractory Acute Lymphoblastic Leukemia
A Phase 2 study testing CART-19 in people with Patients With B Cell ALL, Relapsed or Refractory, With no Available Curative Treatment Options, run by University of Pennsylvania at 1 site in United States.
Trial summary
This is a single center, single arm, open-label phase II study to determine the efficacy and safety of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR/4-1BB) co-stimulatory domains (referred to as CART-19 cells) in adult patients with relapsed or… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Patients With B Cell ALL, Relapsed or Refractory, With no Available Curative Treatment Options
- 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
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Feb 2014to 26 Apr 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
- Signed informed consent form must be obtained prior to any study procedure
- Relapsed or refractory B-cell ALL
- 1st or greater BM relapse OR
- Any marrow relapse after allogeneic HSCT and > 100 days from transplant OR
- For patients with refractory disease:
- < 60 years old that have not achieved a CR after > 2 or more chemotherapy regimens ii. >60 years old that have not achieved a CR after 1 prior chemotherapy regimen d. Patients with Ph+ ALL are eligible if they have failed tyrosine kinase inhibitor therapy
Show all 27Show fewer
- Documentation of CD19 tumor expression in bone marrow or peripheral blood by flow cytometry within 3 months of screening.
- Adequate organ function defined as:
- Creatinine < 1.6 mg/dl
- ALT/AST < 3x upper limit of normal range
- Direct bilirubin <2.0 mg/dl
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea, pulse oxygen > 92% on room air, and DLCO > 40% (corrected for anemia if clinically appropriate)
- Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
- Bone marrow with ≥ 5% lymphoblasts
- Male or female age ≥ 18 years
- A ECOG Performance Status that is either 0 or 1
- No contraindications for leukapheresis.
- Retreatment Inclusion Criteria
- Performance Status 0-1
- Adequate organ system function including:
- Creatinine < 1.6 mg/dl
- ALT/AST < 3x upper limit of normal
- Total Bilirubin < 2.0 mg/dl
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea, pulse oxygen > 92% on room air, and DLCO > 40% (corrected for anemia if clinically appropriate)
- Left Ventricular Ejection Fraction ≥ 40%
- No contraindications for leukapheresis (if required for retreatment)
- Gives voluntary informed consent for retreatment
Who cannot join
- Isolated extramedullary disease relapse
- Active hepatitis B or active hepatitis C
- Class III/IV cardiovascular disability according to the New York Heart Association Classification
- HIV infection
- Active acute or chronic graft-versus-host disease (GVHD) or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
- Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroid and immunosuppressant medications.
Show all 18Show fewer
- Active CNS involvement by malignancy. Note: Patients with history of CNS disease that has been effectively treated will be eligible provided that treatment was >4 weeks before enrollment
- Pregnant or nursing (lactating) women, female study participants of reproductive potential must have a negative serum or urine pregnancy test within 48 hours before infusion
- Participation in a prior investigational study within 4 weeks prior to enrollment or longer if required by local regulation. Participation in non-therapeutic research studies is allowed.
- Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.
- Retreatment Exclusion Criteria
- Pregnant or lactating women.
- Active hepatitis B or hepatitis C
- Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroid or immunosuppressant medications.
- HIV infection
- Patients with active CNS involvement with malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was >4 weeks before enrollment on the retreatment cohort.
- Class III/IV cardiovascular disability according to the New York Heart Association Classification
- Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase II Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCR and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant or RefractoryAcute Lymphoblastic Leukemia
This is a single center, single arm, open-label phase II study to determine the efficacy and safety of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR/4-1BB) co-stimulatory domains (referred to as CART-19 cells) in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Inclusion criteria are designed to include adult patients aged greater than 18 with B cell ALL, relapsed or refractory, with no available curative treatment options (such as autologous or allogeneic stem cell transplantation) who have limited prognosis (greater than 12 weeks survival expectancy) with currently available therapies. The study product is CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCR:41BB administered by a single i.v. infusion of 1 to 5 x 108 transduced CAR T cells.
- Conditions
- Patients With B Cell ALL, Relapsed or Refractory, With no Available Curative Treatment Options
- Being tested
- CART-19
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CART-19Biological
CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCR:41BB administered by a single i.v. infusion of 1 to 5 x 10^8 transduced CAR T cells
CART-19Biological
As of June 2014, dose was reduced to a single dose of 1-5x10^7 CART-19 cells.
CART-19Biological
In the protocol amendment in November 2014, the dose remained 1-5 x 10^7 CART-19 cells, but was revised to be administered via split dosing: 10% on Day 1, 30% on Day 2, 60% on Day 3.
CART-19Biological
In the protocol amendment in May 2015, the dose was changed to 1-5 x 10^8 CART-19 cells administered via split dosing: 10% on Day 1 (1-5x10^7), 30% on Day 2 (3x10^7-1.5x10^8), 60% on Day 3 (6x10^7-3x10^8).
| Study group | Role | What they receive |
|---|---|---|
| Arm1 | Experimental | phase II study to determine the efficacy and safety of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART-19" cells) in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Receives: Biological: CART-19 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Complete Remission Rate at Day 28 After CART-19 Therapy
Overall Complete Remission Rate (ORR) which includes complete remission (CR) and CR with incomplete blood count recovery (CRi) at Day 28.
Overall Complete Remission Rate = CR+ CRi
Measured: 28 Days
Secondary outcomes (1)
Best Overall Response
For the secondary efficacy objectives for this study, the number of patients were computed with a best overall disease response of CR or CRi, where the best overall disease response is defined as the best disease response recorded from the start of the treatment until death, last follow up, relapse or start of new anticancer therapy, whichever comes first.
Measured: from the start of the treatment until death, last follow up, relapse or start of new anticancer therapy, whichever comes first, assessed up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2014 (estimated)
- Study start27 Feb 2014
- Primary completion26 Apr 2018
- Study completion26 Apr 2018
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Patients With B Cell ALL, Relapsed or Refractory, With no Available Curative Treatment OptionsStudies 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
- 42 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, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02030847
- Sponsor's protocol ID
- UPCC 21413, 818626
- Status last verified
- Aug 2019
- First submitted
- 7 Jan 2014
- Last updated
- 22 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 31815579
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 II Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCR and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant or RefractoryAcute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT02030847
- Acronym / sponsor ID
- UPCC 21413, 818626
- Conditions
- Patients With B Cell ALL, Relapsed or Refractory, With no Available Curative Treatment Options
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 27 Feb 2014 (actual)
- Primary completion
- 26 Apr 2018 (actual)
- Study completion
- 26 Apr 2018 (actual)
- First posted
- 9 Jan 2014 (estimated)
- Results
- Posted 24 May 2019
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 II study to determine the efficacy and safety of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR/4-1BB) co-stimulatory domains (referred to as CART-19 cells) in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Inclusion criteria are designed to include adult patients aged greater than 18 with B cell ALL, relapsed or refractory, with no available curative treatment options (such as autologous or allogeneic stem cell transplantation) who have limited prognosis (greater than 12 weeks survival expectancy) with currently available therapies. The study product is CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCR:41BB administered by a single i.v. infusion of 1 to 5 x 108 transduced CAR T cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm1 | Experimental | Biological: CART-19phase II study to determine the efficacy and safety of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART-19" cells) in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Signed informed consent form must be obtained prior to any study procedure
- Relapsed or refractory B-cell ALL
- Documentation of CD19 tumor expression in bone marrow or peripheral blood by flow cytometry within 3 months of screening.
- Adequate organ function defined as:
- Bone marrow with ≥ 5% lymphoblasts
Key exclusion criteria (18 listed)
- Isolated extramedullary disease relapse
- Active hepatitis B or active hepatitis C
- Class III/IV cardiovascular disability according to the New York Heart Association Classification
- HIV infection
- Active acute or chronic graft-versus-host disease (GVHD) or requirement of immunosuppressant medications for GVHD within 4 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-19CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCR:41BB administered by a single i.v. infusion of 1 to 5 x 10^8 transduced CAR T cells | Biological | Arm1 |
| CART-19As of June 2014, dose was reduced to a single dose of 1-5x10^7 CART-19 cells. | Biological | Arm1 |
| CART-19In the protocol amendment in November 2014, the dose remained 1-5 x 10^7 CART-19 cells, but was revised to be administered via split dosing: 10% on Day 1, 30% on Day 2, 60% on Day 3. | Biological | Arm1 |
| CART-19In the protocol amendment in May 2015, the dose was changed to 1-5 x 10^8 CART-19 cells administered via split dosing: 10% on Day 1 (1-5x10^7), 30% on Day 2 (3x10^7-1.5x10^8), 60% on Day 3 (6x10^7-3x10^8). | Biological | Arm1 |
Primary outcome
Overall Complete Remission Rate at Day 28 After CART-19 Therapy
Time frame: 28 Days
Overall Complete Remission Rate (ORR) which includes complete remission (CR) and CR with incomplete blood count recovery (CRi) at Day 28. Overall Complete Remission Rate = CR+ CRi
1 secondary outcome
Best Overall Response
Time frame: from the start of the treatment until death, last follow up, relapse or start of new anticancer therapy, whichever comes first, assessed up to 12 months
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.
- Derived from this study: PubMed 31815579Frey 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.
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
Abramson Cancer Center at Penn Medicine
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 Patients With B Cell ALL, Relapsed or Refractory, With no Available Curative Treatment Options, 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 27 inclusion and 18 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: finished, 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 24 May 2019). 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?
Overall Complete Remission Rate at Day 28 After CART-19 Therapy (time frame: 28 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02030847, which also lists 1 linked publication.
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.