LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL)Early Phase 1NCT02640209
Pilot Trial Of Autologous T Cells Engineered To Express Anti-CD19 Chimeric Antigen Receptor (CART19)In Combination With Ibrutinib In Patients With Relapsed Or Refractory CD19+ Chronic Lymphocytic Leukemia (CLL)Or Small Lymphocytic Lymphoma (SLL)
A Early Phase 1 study testing CART 19 in people with LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL), run by University of Pennsylvania at 1 site in United States.
Trial summary
Open-label pilot study to determine safety and efficacy of CART-19 cells in combination with ibrutinib. The target dose will be 1-5x10xE8 CART-19 transduced cells administered via split dosing: 10% on Day 1, 30% on Day 2, 60% on Day 3. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL)
- What is being tested?
- CART 19
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jan 2016to 16 Jul 2019
- Phase
- Early 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
- Documented CD19+ CLL or SLL
- Successful test expansion -cells (as described in Section 6.1)
- Patients must have failed at least 1 prior regimen before Ibrutinib (not including single agent rituximab or single agent corticosteroids)
- Note: Any relapse after prior autologous SCT will make the patient eligible regardless of other prior therapy.
- Patients must be currently receiving ibrutinib for at least 6 months prior to enrollment in the study and:
- Not experiencing any ≥ grade 2 non-hematologic ibrutinib-related toxicity
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- The best response to ibrutinib therapy must not have exceeded partial response or stable disease (i.e. no CR or CRi)
- Note: Patients carrying a deletion at chromosome 17p (i.e. del[17p]), and/or TP53, BTK, and at the PLCγ2 loci mutations, will be eligible if they are receiving frontline therapy with ibrutinib.
- ECOG Performance status 0 or 1
- 18 years of age and older
- Adequate organ system function including:
- Creatinine < 1.6 mg/dl
- ALT/AST < 3x upper limit of normal
- Total Bilirubin <2.0 mg/dl with the exception of patients with Gilbert syndrome; patients with Gilbert syndrome may be included if their total bilirubin is ≥ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN.
- Patients with relapsed disease after prior allogeneic SCT (myeloablative or nonmyeloablative) will be eligible if they meet all other inclusion criteria and:
- Have no active GVHD and require no immunosuppression
- Are more than 6 months from transplant
- No contraindications for leukapheresis
- Left Ventricular Ejection fraction >40%
- Gives voluntary informed consent
- Subjects of reproductive potential must agree to use acceptable birth control methods.
Who cannot join
- CLL patients with known or suspected transformed disease (i.e. Richter's transformation). Note: biopsy proven absence of transformation is not required.
- 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 or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary.
- Any uncontrolled active medical disorder that would preclude participation as outlined.
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- 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.
- 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.
- 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: Pilot Trial of Autologous T Cells Engineered to Express Anti-CD19 Chimeric Antigen Receptor (CART19) in Combination With Ibrutinib in Patients With Relapsed or Refractory CD19+ CLL or SLL
Open-label pilot study to determine safety and efficacy of CART-19 cells in combination with ibrutinib. The target dose will be 1-5x10xE8 CART-19 transduced cells administered via split dosing: 10% on Day 1, 30% on Day 2, 60% on Day 3. 15 evaluable subjects (adults) with relapsed or refractory CLL/SLL who have achieved partial response or stable disease on ibrutinib therapy will be eligible to receive CART-19 therapy.
- Being tested
- CART 19
- Medical subject headings
- Leukemia, Lymphoid, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CART 19Biological
The target dose range administered in this study is 1-5x108 CART-19 cells administered via split dosing: 10% on Day 1 (1-5x107 CART19), 30% on Day 1 (3x107-1.5x108 CART19), 60% on Day 2 (6x107-3x108 CART19).
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Not described Receives: Biological: CART 19 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Adverse Events
Measured: 26 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2015 (estimated)
- Study start29 Jan 2016
- Primary completion15 Oct 2018
- Study completion16 Jul 2019
Why it stopped: Study is terminated due to administrative reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL)Studies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Saar Gill, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02640209
- Sponsor's protocol ID
- UPCC 18415, 823584
- Status last verified
- May 2020
- First submitted
- 22 Dec 2015
- Last updated
- 22 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Gill S, Vides V, Frey NV, Hexner EO, Metzger S, O'Brien M, Hwang WT, Brogdon JL, Davis MM, Fraietta JA, Gaymon AL, Gladney WL, Lacey SF, Lamontagne A, Mato AR, Maus MV, Melenhorst JJ, Pequignot E, Ruella M, Shestov M, Byrd JC, Schuster SJ, Siegel DL, Levine BL, June CH, Porter DL. Anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia. Blood Adv. 2022 Nov 8;6(21):5774-5785. doi: 10.1182/bloodadvances.2022007317.
PubMed 35349631Frey NV, Gill S, Hexner EO, Schuster S, Nasta S, Loren A, Svoboda J, Stadtmauer E, Landsburg DJ, Mato A, Levine BL, Lacey SF, Melenhorst JJ, Veloso E, Gaymon A, Pequignot E, Shan X, Hwang WT, June CH, Porter DL. Long-Term Outcomes From a Randomized Dose Optimization Study of Chimeric Antigen Receptor Modified T Cells in Relapsed Chronic Lymphocytic Leukemia. J Clin Oncol. 2020 Sep 1;38(25):2862-2871. doi: 10.1200/JCO.19.03237. Epub 2020 Apr 16.
PubMed 32298202
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 Trial of Autologous T Cells Engineered to Express Anti-CD19 Chimeric Antigen Receptor (CART19) in Combination With Ibrutinib in Patients With Relapsed or Refractory CD19+ CLL or SLL
- ClinicalTrials.gov ID
- NCT02640209
- Acronym / sponsor ID
- UPCC 18415, 823584
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study is terminated due to administrative reasons.
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 29 Jan 2016 (actual)
- Primary completion
- 15 Oct 2018 (actual)
- Study completion
- 16 Jul 2019 (actual)
- First posted
- 28 Dec 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.
Open-label pilot study to determine safety and efficacy of CART-19 cells in combination with ibrutinib. The target dose will be 1-5x10xE8 CART-19 transduced cells administered via split dosing: 10% on Day 1, 30% on Day 2, 60% on Day 3. 15 evaluable subjects (adults) with relapsed or refractory CLL/SLL who have achieved partial response or stable disease on ibrutinib therapy will be eligible to receive CART-19 therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Biological: CART 19 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Documented CD19+ CLL or SLL
- Successful test expansion -cells (as described in Section 6.1)
- Patients must have failed at least 1 prior regimen before Ibrutinib (not including single agent rituximab or single agent corticosteroids)
- Patients must be currently receiving ibrutinib for at least 6 months prior to enrollment in the study and:
- ECOG Performance status 0 or 1
Key exclusion criteria (11 listed)
- CLL patients with known or suspected transformed disease (i.e. Richter's transformation). Note: biopsy proven absence of transformation is not required.
- 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 or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary.
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 19The target dose range administered in this study is 1-5x108 CART-19 cells administered via split dosing: 10% on Day 1 (1-5x107 CART19), 30% on Day 1 (3x107-1.5x108 CART19), 60% on Day 2 (6x107-3x108 CART19). | Biological | Arm 1 |
Primary outcome
Number of Adverse Events
Time frame: 26 months
Results and safety
The study was stopped early (reason given: Study is terminated due to administrative reasons.). 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 35349631Gill S, Vides V, Frey NV, Hexner EO, Metzger S, O'Brien M, Hwang WT, Brogdon JL, Davis MM, Fraietta JA, Gaymon AL, Gladney WL, Lacey SF, Lamontagne A, Mato AR, Maus MV, Melenhorst JJ, Pequignot E, Ruella M, Shestov M, Byrd JC, Schuster SJ, Siegel DL, Levine BL, June CH, Porter DL. Anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia. Blood Adv. 2022 Nov 8;6(21):5774-5785. doi: 10.1182/bloodadvances.2022007317.
- Derived from this study: PubMed 32298202Frey NV, Gill S, Hexner EO, Schuster S, Nasta S, Loren A, Svoboda J, Stadtmauer E, Landsburg DJ, Mato A, Levine BL, Lacey SF, Melenhorst JJ, Veloso E, Gaymon A, Pequignot E, Shan X, Hwang WT, June CH, Porter DL. Long-Term Outcomes From a Randomized Dose Optimization Study of Chimeric Antigen Receptor Modified T Cells in Relapsed Chronic Lymphocytic Leukemia. J Clin Oncol. 2020 Sep 1;38(25):2862-2871. doi: 10.1200/JCO.19.03237. Epub 2020 Apr 16.
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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.
Saar Gill, 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 Early Phase 1 study testing CART 19 in people with LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL), 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 21 inclusion and 11 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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: Study is terminated due to administrative reasons.). 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: 26 months). 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 NCT02640209, which also lists 2 linked publications.
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.