Acute Lymphocytic LeukemiaPhase 1NCT02374333
Pilot Study of Redirected Autologous T Cells Engineered to Contain Humanized Anti-CD19 in Patients With Relapsed or Refractory CD19+ Leukemia and Lymphoma Previously Treated With Cell Therapy
A Phase 1 study testing huCART19 in people with Acute Lymphocytic Leukemia and Diffuse Large Cell Lymphoma, run by University of Pennsylvania at 1 site in United States.
Trial summary
This is a pilot study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) in patients with relapsed or refractory CD19+ leukemia and lymphoma that was previously treated with cell therapy. Read more about this study
- Who is it for?
- Ages 1 year to 24 years
- Conditions the study is for
- Acute Lymphocytic Leukemia, Diffuse Large Cell Lymphoma
- What is being tested?
- huCART19
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Mar 2014to 2 Sep 2021
- 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 1 year to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male and female subjects with documented CD19+ B cell malignancies and 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:
- Eligible diseases: CD19+ leukemia or lymphoma. In general, these will be patients with:
- ALL without curative options for therapy, including those not eligible for allogeneic SCT. Patient may be in any complete response, or patient may have active disease but responding or stable after most recent therapy.The intent is not to enroll patients with no degree of disease control or rapidly increasing disease burden between enrollment and cell infusion.
- Diffuse large cell lymphoma or other high-grade NHL, previously identified as CD19+ including residual disease after primary therapy and not eligible for autologous SCT; relapsed after prior autologous SCT; beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT.
- Patients previously treated with B cell directed engineered cell therapy are eligible if they meet one of the following criteria:
- partial response or no response to prior cell therapy
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- relapsed after prior cell therapy
- demonstrated B cell recovery suggesting loss of engineered cells.
- Documented CD19 expression (after previous B cell directed cell therapy, if applicable)
- Age 1 to 24 years
- Expected survival > 12 weeks
- Creatinine < 2.5 mg/dl and less than 2.5x normal for age
- Bilirubin <2.0 mg/dl
- Adequate pulmonary function defined as < Grade 3 hypoxia
- Adequate cardiac function defined as LVSF ≥ 28% confirmed by ECHO
- Adequate performance status (Lansky or Karnofsky score ≥50)
- Patients with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and
- Have no active GVHD and require no immunosuppression
- Are more than 4 months from transplant (6 months at infusion)
- Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy
- For those patients who require leukapheresis for T cell collection (i.e. no previously collected product exists), adequate venous access for apheresis or eligible for appropriate catheter placement, and no other contraindications for leukapheresis.
- Voluntary informed consent is given.
Who cannot join
- 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 at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
- Presence of grade 2-4 acute or extensive chronic GVHD.
- Under treatment for GVHD.
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- CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity
- Any uncontrolled active medical disorder that would preclude participation as outlined.
- HIV infection
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Pilot Study of Redirected Autologous T Cells Engineered to Contain Humanized Anti-CD19 Attached to TCRζ and 4-1BB Signaling Domains in Patients With Relapsed or Refractory CD19+ Leukemia and Lymphoma Previously Treated With Cell Therapy
This is a pilot study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) in patients with relapsed or refractory CD19+ leukemia and lymphoma that was previously treated with cell therapy. This study is targeting pediatric patients aged 1-24 years with CD19+ B cell malignancies with no available curative treatment options (such as autologous or allogeneic stem cell transplantation) who have a limited prognosis with currently available therapies and were previously treated with a B cell directed engineered cell therapy product.
- Being tested
- huCART19
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
huCART19Biological
Also called huCTL019
| Study group | Role | What they receive |
|---|---|---|
| huCART19 | Experimental | CART19 cells transduced with a lentiviral vector to express humanized anti-CD19 administered by IV injection Receives: Biological: huCART19 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of study related adverse events defined as NCI CTCAE 4.0 > grade 3 possibly, probably, or definitely related to study treatment.
Measured: Study treatment until Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2015 (estimated)
- Study start25 Mar 2014
- Primary completion2 Sep 2021
- Study completion2 Sep 2021
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 Acute Lymphocytic 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
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Carl June, MD, Study chair, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02374333
- Sponsor's protocol ID
- 13BT022, 819851
- Status last verified
- Sep 2021
- First submitted
- 23 Feb 2015
- Last updated
- 23 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PubMed 34515338Myers RM, Li Y, Barz Leahy A, Barrett DM, Teachey DT, Callahan C, Fasano CC, Rheingold SR, DiNofia A, Wray L, Aplenc R, Baniewicz D, Liu H, Shaw PA, Pequignot E, Getz KD, Brogdon JL, Fesnak AD, Siegel DL, Davis MM, Bartoszek C, Lacey SF, Hexner EO, Chew A, Wertheim GB, Levine BL, June CH, Grupp SA, Maude SL. Humanized CD19-Targeted Chimeric Antigen Receptor (CAR) T Cells in CAR-Naive and CAR-Exposed Children and Young Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2021 Sep 20;39(27):3044-3055. doi: 10.1200/JCO.20.03458. Epub 2021 Jun 22.
PubMed 34156874
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Redirected Autologous T Cells Engineered to Contain Humanized Anti-CD19 Attached to TCRζ and 4-1BB Signaling Domains in Patients With Relapsed or Refractory CD19+ Leukemia and Lymphoma Previously Treated With Cell Therapy
- ClinicalTrials.gov ID
- NCT02374333
- Acronym / sponsor ID
- 13BT022, 819851
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 25 Mar 2014 (actual)
- Primary completion
- 2 Sep 2021 (actual)
- Study completion
- 2 Sep 2021 (actual)
- First posted
- 27 Feb 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 pilot study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) in patients with relapsed or refractory CD19+ leukemia and lymphoma that was previously treated with cell therapy. This study is targeting pediatric patients aged 1-24 years with CD19+ B cell malignancies with no available curative treatment options (such as autologous or allogeneic stem cell transplantation) who have a limited prognosis with currently available therapies and were previously treated with a B cell directed engineered cell therapy product.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| huCART19 | Experimental | Biological: huCART19CART19 cells transduced with a lentiviral vector to express humanized anti-CD19 administered by IV injection |
Who may qualify
- Ages
- 1 year to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (22 listed)
- Male and female subjects with documented CD19+ B cell malignancies and 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:
- Eligible diseases: CD19+ leukemia or lymphoma. In general, these will be patients with:
- Patients previously treated with B cell directed engineered cell therapy are eligible if they meet one of the following criteria:
- Documented CD19 expression (after previous B cell directed cell therapy, if applicable)
- Age 1 to 24 years
Key exclusion criteria (9 listed)
- 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 at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
- Presence of grade 2-4 acute or extensive chronic GVHD.
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 |
|---|---|---|
| huCART19Also: huCTL019 | Biological | huCART19 |
Primary outcome
Occurrence of study related adverse events defined as NCI CTCAE 4.0 > grade 3 possibly, probably, or definitely related to study treatment.
Time frame: Study treatment until Week 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2021.
- Derived from this study: PubMed 34515338Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
- Derived from this study: PubMed 34156874Myers RM, Li Y, Barz Leahy A, Barrett DM, Teachey DT, Callahan C, Fasano CC, Rheingold SR, DiNofia A, Wray L, Aplenc R, Baniewicz D, Liu H, Shaw PA, Pequignot E, Getz KD, Brogdon JL, Fesnak AD, Siegel DL, Davis MM, Bartoszek C, Lacey SF, Hexner EO, Chew A, Wertheim GB, Levine BL, June CH, Grupp SA, Maude SL. Humanized CD19-Targeted Chimeric Antigen Receptor (CAR) T Cells in CAR-Naive and CAR-Exposed Children and Young Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2021 Sep 20;39(27):3044-3055. doi: 10.1200/JCO.20.03458. Epub 2021 Jun 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.
Carl June, MD study chair
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 1 study testing huCART19 in people with Acute Lymphocytic Leukemia and Diffuse Large Cell Lymphoma, 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 22 inclusion and 9 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 23 Sep 2021. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Occurrence of study related adverse events defined as NCI CTCAE 4.0 > grade 3 possibly, probably, or definitely related to study treatment. (time frame: Study treatment until Week 24). 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 NCT02374333, 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 23 Sep 2021.