Relapsed or Refractory B-cell Acute Lymphoblastic LeukemiaPhase 1NCT02588456
Pilot Study of Autologous Anti-CD22 Chimeric Antigen Receptor Redirected T Cells In Patients With Chemotherapy Resistant Or Refractory Acute Lymphoblastic Leukemia
A Phase 1 study testing CART22 cells in people with Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia, run by University of Pennsylvania at 1 site in United States.
Trial summary
This is a single center, single arm, open-label pilot study to determine the feasibility and safety of a single dose of autologous T cells expressing CD22 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART22" cells) administered in split fractions, in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia
- What is being tested?
- CART22 cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to Sep 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 research procedure.
- Relapsed or refractory B-cell ALL:
- 1st or greater BM relapse OR b. Any marrow relapse after allogeneic HSCT and > 100 days from transplant OR c. For patients with refractory disease: i. < 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 are intolerant to or have failed tyrosine kinase inhibitor therapy.
- Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy.
- Documentation of CD22 expression on malignant cells at relapse.
- Adequate organ function defined as:
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- 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)
- Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
- Evidence of disease by standard morphologic or by MRD criteria.
- Male or female age ≥ 18 years.
- ECOG Performance Status that is either 0 or 1.
- No contraindications for leukapheresis.
- Subjects of reproductive potential must agree to use acceptable birth control methods.
Who cannot join
- Active hepatitis B or active hepatitis C.
- HIV Infection.
- Class III/IV cardiovascular disability according to the New York Heart Association Classification.
- Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of enrollment.
- Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
- Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary. For additional details regarding use of steroid and immunosuppressant medications.
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- CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
- Pregnant or nursing (lactating) women.
- Receipt of a prior investigational study agent within 4 weeks prior to enrollment. *Note- patients who have received anti-CD19 CART cells (e.g. CART19/CTL019) on an investigational study where cell infusion occurred greater than 4 weeks before the screening visit are NOT excluded.
- 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
This is a single center, single arm, open-label pilot study to determine the feasibility and safety of a single dose of autologous T cells expressing CD22 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART22" cells) administered in split fractions, in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
- Being tested
- CART22 cells
- Medical subject headings
- Recurrence, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CART22 cellsBiological
CART22 cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB administered by IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Not described Receives: Biological: CART22 cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Adverse Events
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2015 (estimated)
- Study startOct 2015
- Primary completionSep 2017
- Study completionSep 2017
Why it stopped: This study was terminated due to lack of efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsed or Refractory B-cell Acute Lymphoblastic LeukemiaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 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
- NCT02588456
- Sponsor's protocol ID
- UPCC 31415, 822967
- Status last verified
- Jan 2018
- First submitted
- 26 Oct 2015
- Last updated
- 22 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Singh N, Frey NV, Engels B, Barrett DM, Shestova O, Ravikumar P, Cummins KD, Lee YG, Pajarillo R, Chun I, Shyu A, Highfill SL, Price A, Zhao L, Peng L, Granda B, Ramones M, Lu XM, Christian DA, Perazzelli J, Lacey SF, Roy NH, Burkhardt JK, Colomb F, Damra M, Abdel-Mohsen M, Liu T, Liu D, Standley DM, Young RM, Brogdon JL, Grupp SA, June CH, Maude SL, Gill S, Ruella M. Antigen-independent activation enhances the efficacy of 4-1BB-costimulated CD22 CAR T cells. Nat Med. 2021 May;27(5):842-850. doi: 10.1038/s41591-021-01326-5. Epub 2021 Apr 22.
PubMed 33888899
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
- Pilot Study of Autologous Anti-CD22 Chimeric Antigen Receptor Redirected T Cells In Patients With Chemotherapy Resistant Or Refractory Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT02588456
- Acronym / sponsor ID
- UPCC 31415, 822967
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated due to lack of efficacy
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- Sep 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 27 Oct 2015 (estimated)
- Results
- Not posted in the source record
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 pilot study to determine the feasibility and safety of a single dose of autologous T cells expressing CD22 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART22" cells) administered in split fractions, in adult patients with relapsed or refractory B-cell 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 |
|---|---|---|
| Single Arm | Experimental | Biological: CART22 cells |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Signed informed consent form must be obtained prior to any research procedure.
- Relapsed or refractory B-cell ALL:
- Documentation of CD22 expression on malignant cells at relapse.
- Adequate organ function defined as:
- Evidence of disease by standard morphologic or by MRD criteria.
Key exclusion criteria (10 listed)
- Active hepatitis B or active hepatitis C.
- HIV Infection.
- Class III/IV cardiovascular disability according to the New York Heart Association Classification.
- Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of enrollment.
- Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
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 |
|---|---|---|
| CART22 cellsCART22 cells transduced with a lentiviral vector to express anti-CD22 scFv TCRz:41BB administered by IV infusion. | Biological | Single Arm |
Primary outcome
Number of Adverse Events
Time frame: 3 years
Results and safety
The study was stopped early (reason given: This study was terminated due to lack of efficacy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
- Derived from this study: PubMed 33888899Singh N, Frey NV, Engels B, Barrett DM, Shestova O, Ravikumar P, Cummins KD, Lee YG, Pajarillo R, Chun I, Shyu A, Highfill SL, Price A, Zhao L, Peng L, Granda B, Ramones M, Lu XM, Christian DA, Perazzelli J, Lacey SF, Roy NH, Burkhardt JK, Colomb F, Damra M, Abdel-Mohsen M, Liu T, Liu D, Standley DM, Young RM, Brogdon JL, Grupp SA, June CH, Maude SL, Gill S, Ruella M. Antigen-independent activation enhances the efficacy of 4-1BB-costimulated CD22 CAR T cells. Nat Med. 2021 May;27(5):842-850. doi: 10.1038/s41591-021-01326-5. Epub 2021 Apr 22.
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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
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 1 study testing CART22 cells in people with Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia, 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 16 inclusion and 10 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: This study was terminated due to lack of efficacy). Results are not available in the source record.
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?
Number of Adverse Events (time frame: 3 years). 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 NCT02588456, 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.