Hodgkin LymphomaEarly Phase 1NCT02624258
Pilot Study of Non-Viral, RNA-Redirected Autologous T Cells in Patients With Refractory or Relapsed Hodgkin Lymphoma
A Early Phase 1 study testing CD19 RNA redirected autologous T-cells (RNA CART19 cells) in people with Hodgkin Lymphoma, run by University of Pennsylvania at 1 site in United States.
Trial summary
Pilot open-label study to estimate the feasibility, safety and efficacy of intravenously administered, RNA electroporated autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains (referred to as "RNA CART19") in Hodgkin Lymphoma (HL) patients. Read more about this study
- Who is it for?
- Ages 18 to 24 years
- Conditions the study is for
- Hodgkin Lymphoma
- What is being tested?
- CD19 RNA redirected autologous T-cells (RNA CART19 cells)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to 6 Dec 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 to 24 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female subjects with HL with no available curative treatment options (such as autologous SCT) who have a limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled.
- HL with biopsy-proven relapse or refractory disease who are unresponsive to or intolerant of at least one line of standard salvage therapy;
- Patients must have evaluable disease by radiologic imaging (FDG PET-CT or FDG PET-MRI) within 42 day of enrollment; evaluable includes both assessable and/or measurable disease
- Age 18 to 24 years. Patients ages 22-24 will only be enrolled if they are currently being treated at CHOP or another pediatric facility/oncologist.
- Expected survival > 12 weeks at time of screening
- Adequate organ function defined as:
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- Renal function defined as:
- Creatinine clearance or radioisotope GFR > 60 mL/min/1.73 m2 OR
- Serum creatinine: < 1.7mg/dL (male subjects) or < 1.4mg/dL (female subjects)
- ALT < 5 times the ULN for age
- Total Bilirubin < 2.0 mg/dl
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation > 94% on room air
- 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 6 months from transplant 6) Karnofsky performance status ≥ 50 at screening
- Left Ventricular Shortening Fraction (LVSF) > 28% confirmed by echocardiogram, or Left Ventricular Ejection Fraction (LVEF) > 45% confirmed by echocardiogram or MUGA
- Signed written informed consent must be obtained prior to any study procedures
- Successful T cell test expansion (to be performed as part of inclusion criteria until 3 subjects meet all enrollment criteria)
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 pregnancy test at enrollment. A urine pregnancy test will be performed within 48 hours before the RNA CART19 infusion.
- Uncontrolled active infection.
- Active hepatitis B or hepatitis C infection.
- Any uncontrolled active medical disorder that would preclude participation as outlined.
- HIV infection.
- Patients with known active CNS involvement by malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was >4 weeks before enrollment
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- Patients in complete remission with no evidence by radiologic imaging of disease.
- History of allergy to murine proteins
- History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
- Anti-CD20 monoclonal antibody therapy within the last 3 months, or absence of circulating B cells
- Unstable angina and/or myocardial infarction within 6 months prior to screening.
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 Non-Viral, RNA-Redirected Autologous T Cells Engineered to Contain Anti-CD19 Linked to TCR and 4-1BB Signaling Domains in Patients With Refractory or Relapsed Hodgkin Lymphoma
Pilot open-label study to estimate the feasibility, safety and efficacy of intravenously administered, RNA electroporated autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains (referred to as "RNA CART19") in Hodgkin Lymphoma (HL) patients. Subjects will be treated with IV administration of RNA anti-CD19 CAR T cells for a total of six doses over 3 weeks.
Read the detailed description
The study will enroll 10 evaluable patients. Evaluable patients are those who have received at least 1 of the 6 RNA CART19 doses at the protocol-specified level. Important safety data can be collected even if a patient receives only one RNA CART19 dose. Subjects (n = 10) will receive up to six IV doses of 8x105-1.5x106 RNA CART19 cells/kg/dose for subjects<80kg and 1x108 RNA CART19 cells/dose (±20%) for subjects ≥80kg.
The RNA CART19 doses and mid-treatment single dose cyclophosphamide will be administered on Mondays, Wednesdays or Fridays. Dosing can be initiated on any of those days. Subjects will be infused in a staggered fashion at two week intervals; that is, the next subject cannot be infused prior to two weeks since the last infusion of the previous subject.
- Conditions
- Hodgkin Lymphoma
- Being tested
- CD19 RNA redirected autologous T-cells (RNA CART19 cells)
- Medical subject headings
- Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD19 RNA redirected autologous T-cells (RNA CART19 cells)Biological
Subjects will be treated with IV administration of RNA anti-CD19 CAR T cells for a total of six doses over 3 weeks. The first dose will be administered 1-4 days after infusion of cyclophosphamide 30mg/kg.
| Study group | Role | What they receive |
|---|---|---|
| RNA CART19 cells | Experimental | CD19 RNA redirected autologous T-cells (RNA CART19 cells) Receives: Biological: CD19 RNA redirected autologous T-cells (RNA CART19 cells) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events, defined as NCI CTCAE V4 > Grade 3
Occurrence of study related adverse events, defined as NCI CTCAE V4 > grade 3 signs/symptoms, laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the first cyclophosphamide infusion until Month 4.
Measured: Month 4 post-CART19 Infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2015 (estimated)
- Study startNov 2015
- Primary completion5 Jun 2019
- Study completion6 Dec 2019
Why it stopped: Principal Investigator decision to stop trial
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 Hodgkin LymphomaStudies 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
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital of Philadelphia
- Responsible party
- Sponsor
- Investigators
- Susan Rheingold, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02624258
- Sponsor's protocol ID
- 14BT055, 821157
- Status last verified
- May 2020
- First submitted
- 1 Dec 2015
- Last updated
- 21 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Svoboda J, Rheingold SR, Gill SI, Grupp SA, Lacey SF, Kulikovskaya I, Suhoski MM, Melenhorst JJ, Loudon B, Mato AR, Nasta SD, Landsburg DJ, Youngman MR, Levine BL, Porter DL, June CH, Schuster SJ. Nonviral RNA chimeric antigen receptor-modified T cells in patients with Hodgkin lymphoma. Blood. 2018 Sep 6;132(10):1022-1026. doi: 10.1182/blood-2018-03-837609. Epub 2018 Jun 20.
PubMed 29925499
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Non-Viral, RNA-Redirected Autologous T Cells Engineered to Contain Anti-CD19 Linked to TCR and 4-1BB Signaling Domains in Patients With Refractory or Relapsed Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT02624258
- Acronym / sponsor ID
- 14BT055, 821157
- Conditions
- Hodgkin Lymphoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Principal Investigator decision to stop trial
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Children's Hospital of Philadelphia
- Study start
- Nov 2015
- Primary completion
- 5 Jun 2019 (actual)
- Study completion
- 6 Dec 2019 (actual)
- First posted
- 8 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.
Pilot open-label study to estimate the feasibility, safety and efficacy of intravenously administered, RNA electroporated autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains (referred to as "RNA CART19") in Hodgkin Lymphoma (HL) patients. Subjects will be treated with IV administration of RNA anti-CD19 CAR T cells for a total of six doses over 3 weeks.
Detailed description
The study will enroll 10 evaluable patients. Evaluable patients are those who have received at least 1 of the 6 RNA CART19 doses at the protocol-specified level. Important safety data can be collected even if a patient receives only one RNA CART19 dose. Subjects (n = 10) will receive up to six IV doses of 8x105-1.5x106 RNA CART19 cells/kg/dose for subjects<80kg and 1x108 RNA CART19 cells/dose (±20%) for subjects ≥80kg.
The RNA CART19 doses and mid-treatment single dose cyclophosphamide will be administered on Mondays, Wednesdays or Fridays. Dosing can be initiated on any of those days. Subjects will be infused in a staggered fashion at two week intervals; that is, the next subject cannot be infused prior to two weeks since the last infusion of the previous subject.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RNA CART19 cells | Experimental | Biological: CD19 RNA redirected autologous T-cells (RNA CART19 cells)CD19 RNA redirected autologous T-cells (RNA CART19 cells) |
Who may qualify
- Ages
- 18 to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- Male or female subjects with HL with no available curative treatment options (such as autologous SCT) who have a limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled.
- Age 18 to 24 years. Patients ages 22-24 will only be enrolled if they are currently being treated at CHOP or another pediatric facility/oncologist.
- Expected survival > 12 weeks at time of screening
- Adequate organ function defined as:
- Renal function defined as:
Key exclusion criteria (11 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 pregnancy test at enrollment. A urine pregnancy test will be performed within 48 hours before the RNA CART19 infusion.
- Uncontrolled active infection.
- Active hepatitis B or hepatitis C infection.
- Any uncontrolled active medical disorder that would preclude participation as outlined.
- HIV infection.
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 |
|---|---|---|
| CD19 RNA redirected autologous T-cells (RNA CART19 cells)Subjects will be treated with IV administration of RNA anti-CD19 CAR T cells for a total of six doses over 3 weeks. The first dose will be administered 1-4 days after infusion of cyclophosphamide 30mg/kg. | Biological | RNA CART19 cells |
Primary outcome
Incidence of Treatment-Emergent Adverse Events, defined as NCI CTCAE V4 > Grade 3
Time frame: Month 4 post-CART19 Infusion
Occurrence of study related adverse events, defined as NCI CTCAE V4 > grade 3 signs/symptoms, laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the first cyclophosphamide infusion until Month 4.
Results and safety
The study was stopped early (reason given: Principal Investigator decision to stop trial). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2020.
- Derived from this study: PubMed 29925499Svoboda J, Rheingold SR, Gill SI, Grupp SA, Lacey SF, Kulikovskaya I, Suhoski MM, Melenhorst JJ, Loudon B, Mato AR, Nasta SD, Landsburg DJ, Youngman MR, Levine BL, Porter DL, June CH, Schuster SJ. Nonviral RNA chimeric antigen receptor-modified T cells in patients with Hodgkin lymphoma. Blood. 2018 Sep 6;132(10):1022-1026. doi: 10.1182/blood-2018-03-837609. Epub 2018 Jun 20.
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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.
Susan Rheingold, MD principal investigator
Children's Hospital of Philadelphia
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 CD19 RNA redirected autologous T-cells (RNA CART19 cells) in people with Hodgkin 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 18 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 21 May 2020. 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: Principal Investigator decision to stop trial). 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?
Incidence of Treatment-Emergent Adverse Events, defined as NCI CTCAE V4 > Grade 3 (time frame: Month 4 post-CART19 Infusion). 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 NCT02624258, 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 21 May 2020.