Multiple MyelomaPhase 1/2NCT01892293
CT Antigen TCR-Engineered T Cells for Myeloma
A Phase 1/2 study testing Treatment with NY-ESO-1c259-modified T cells in people with Multiple Myeloma, run by Adaptimmune at 2 sites in United States.
Trial summary
This study will enroll patients with multiple myeloma who have received prior therapy for their disease but their disease has progressed or relapsed. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Treatment with NY-ESO-1c259-modified T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesUnited States
- Study dates
- 15 Oct 2013to 9 Apr 2018
- Phase
- Phase 1/2
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Written informed consent must be obtained from all patients before entry into the study
- 2. Patients must have a diagnosis of myeloma (see Appendix A for diagnostic criteria).
- 3. Patients must have progressive or active disease following prior therapy for their myeloma which:
- includes an IMiD and proteasome inhibitor as separate lines or a combined line of therapy
- May include prior auto-SCT but not prior allo-SCT
- Patients who have failed second or third line therapy and beyond, such as DPACE, and who are experiencing a partial response rather than progressive disease are also eligible.
Show all 9Show fewer
- 4. Patients must have measurable disease on study entry. Measurable disease may include quantifiable or detectable levels of serum or urine paraprotein. For patients with minimally secretory disease on study entry, serum free kappa or lambda light chain levels, or the serum free light chain ratio may be measured and used for disease monitoring if abnormal.
- 5. Patients must be HLA-A201 as determined by a CLIA certified (or equivalent) clinical laboratory. (This determination will be made under a pre-enrollment screening ICF)
- 6. Patients must have confirmed expression of NY-ESO-1 and/or LAGE-1 by RT-PCR, immunohistochemistry or quantigene analysis. (This determination will be made under a pre-enrollment screening ICF)
Who cannot join
- 1. Pregnant or nursing females 2. HIV or HTLV-1/2 seropositivity 3. Known history of myelodysplasia 4. Known history of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy).
- 5. Active Infection with HBV or HCV
- Active hepatitis B infection as determined by test for hepatitis B surface antigen.
- Active hepatitis C. Patients will be screened for HCV antibody. If the HCV antibody is positive, a screening HCV RNA by any RT PCR or bDNA assay must be performed at screening by a local laboratory with a CLIA certification or its equivalent. Eligibility will be determined based on a negative screening value. The test is not required if documentation of a negative result of a HCV RNA test performed within 60 days prior to screening is provided.
- 6. Prior allogeneic transplant 7. History of severe autoimmune disease requiring steroids or other immunosuppressive treatments.
- 8. Active immune-mediated diseases including: connective tissue diseases, uveitis, sarcoidosis, inflammatory bowel disease, multiple sclerosis.
- 9. Evidence or history of other significant cardiac, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease which would likely increase the risks of participating in the study. The specific type of stress test will be selected at the PI's discretion.
- 10. Active bacterial or systemic viral or fungal infections.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Greenebaum Cancer Center, University of Maryland
Baltimore, Maryland, 21201
City of Hope
Duarte, California, 91010
About this study
Official title: A Phase I/IIa, Open Label, Multiple Site Clinical Trial Evaluating the Safety and Activity of Engineered Autologous T Cells Expressing an Affinity-enhanced TCR Specific for NY-ESO-1 and LAGE-1 in Patients With Relapsed or Progressive Disease in Multiple Myeloma
This study will enroll patients with multiple myeloma who have received prior therapy for their disease but their disease has progressed or relapsed.
Read the detailed description
The primary objective of the study is to evaluate the safety and tolerability of autologous genetically modified T cells transduced to express the high affinity NY-ESO-1c259 TCR in HLA-A201 patients. Eligibility screening will be performed in two steps. First, patients will undergo prescreening to determine if they have the correct HLA type in order to respond to the engineered T cell therapy, and to test for presence of the target antigen, NY-ESO-1 and LAGE-1, in their tumor cells. Patients, who are HLA-A201 positive and test positive for expression of NY-ESO-1 and/or LAGE-1 in their myeloma tumor will move on to complete all screening procedures to determine eligibility for the study.
Patients will initially undergo a steady-state mononuclear cell apheresis for T cell collection. About 3-4 weeks later (to allow expansion/engineering/releasing the engineered T cells), patients will receive a short course of cytoreductive chemotherapy prior to receiving the engineered T cell infusion, comprised of 1.5 gm/m2 of cyclophosphamide, mesna will be given if in accordance with institutional standards.
At day 0, patients will receive a dose of ≥0.1-1 x 1010 anti-CD3/anti-CD28-costimulated autologous T cells which have been genetically modified to express affinity-enhanced NY-ESO-1 T cell receptors (TCRs). A minimum dose of 0.1≤x<1 x 109 will be permitted. Patients receiving this low dose level will be evaluated separately for safety and efficacy.
Patients will undergo myeloma restaging approximately 1 week prior to the T cell infusion, and post infusion at days +28, +42 (week 6), +100 and 6 months post infusion and then every 3 months until relapse/progression or until 1 year, whenever comes first. At this point, patients will be followed semi-annually for up to 5 years and then annually for long term follow-up for monitoring for delayed adverse events until 15 years after receiving the genetically modified T cells, in accordance with FDA Guidelines.
- Conditions
- Multiple Myeloma
- Being tested
- Treatment with NY-ESO-1c259-modified T cells
- Keywords
- Multiple Myeloma, Autologous stem cell transplantation, Received initial treatment previously
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment with NY-ESO-1c259-modified T cellsDrug
An intended total dose of ≥0.1-1e10 total cells will be administered as a single infusion. A low dose infusion of 1e8 to < 1e9 will be allowed for patients if cells do not expand sufficiently to reach the target dose range.
For patients whose disease progresses and whose tumor still expresses tumor antigen and HLA-A201, a second infusion of up to 5e10 cells may be given.
| Study group | Role | What they receive |
|---|---|---|
| Autologous genetically modified T cells | Experimental | Patients with a confirmed diagnosis of myeloma, with measurable disease, and who have received prior therapy for their myeloma that includes an IMiDs and a proteasome inhibitor and who have relapsed or progressive disease, will receive treatment with NY-ESO-1c259-modified T cells. An intended total dose of ≥0.1-1e10 total cells will be administered as a single infusion. A low dose infusion of 1e8 to < 1e9 will be allowed for patients if cells do not expand sufficiently to reach the target dose range. Receives: Drug: Treatment with NY-ESO-1c259-modified T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events Related to Study Treatment
Number of Participants with NCI CTCAE Version 4.0 Adverse Events related to study treatment greater than or equal to Grade 3
Measured: Up to 12 months
Secondary outcomes (2)
Evaluate the Direct Anti-tumor Activity of NY-ESO-1ᶜ²⁵⁹T
Number of participants with response post-infusion as assessed by international uniform response criteria
Measured: 180 days
Peak Persistence of Modified T-cells in the Peripheral Blood
Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood (copies of WPRE per µg of genomic PBMC DNA)
Measured: Days 1, 3, 5, 8, 15, 22, 29, 43, 101, 130 181, every 3 months thereafter
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2013 (estimated)
- Study start15 Oct 2013
- Primary completion10 Dec 2014
- Study completion9 Apr 2018
Why it stopped: Sponsor Decision
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.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Adaptimmune
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Edward Stadtmauer, MD, Study chair, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01892293
- Sponsor's protocol ID
- ADP-0011-002
- Status last verified
- Jan 2019
- First submitted
- 27 Jun 2013
- Last updated
- 10 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa, Open Label, Multiple Site Clinical Trial Evaluating the Safety and Activity of Engineered Autologous T Cells Expressing an Affinity-enhanced TCR Specific for NY-ESO-1 and LAGE-1 in Patients With Relapsed or Progressive Disease in Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01892293
- Acronym / sponsor ID
- ADP-0011-002
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Autologous stem cell transplantation, Received initial treatment previously
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 6 participants (actual)
- Lead sponsor
- AdaptimmuneIndustry (pharma, biotech, devices)
- Study start
- 15 Oct 2013 (actual)
- Primary completion
- 10 Dec 2014 (actual)
- Study completion
- 9 Apr 2018 (actual)
- First posted
- 4 Jul 2013 (estimated)
- Results
- Posted 24 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will enroll patients with multiple myeloma who have received prior therapy for their disease but their disease has progressed or relapsed.
Detailed description
The primary objective of the study is to evaluate the safety and tolerability of autologous genetically modified T cells transduced to express the high affinity NY-ESO-1c259 TCR in HLA-A201 patients. Eligibility screening will be performed in two steps. First, patients will undergo prescreening to determine if they have the correct HLA type in order to respond to the engineered T cell therapy, and to test for presence of the target antigen, NY-ESO-1 and LAGE-1, in their tumor cells. Patients, who are HLA-A201 positive and test positive for expression of NY-ESO-1 and/or LAGE-1 in their myeloma tumor will move on to complete all screening procedures to determine eligibility for the study.
Patients will initially undergo a steady-state mononuclear cell apheresis for T cell collection. About 3-4 weeks later (to allow expansion/engineering/releasing the engineered T cells), patients will receive a short course of cytoreductive chemotherapy prior to receiving the engineered T cell infusion, comprised of 1.5 gm/m2 of cyclophosphamide, mesna will be given if in accordance with institutional standards.
At day 0, patients will receive a dose of ≥0.1-1 x 1010 anti-CD3/anti-CD28-costimulated autologous T cells which have been genetically modified to express affinity-enhanced NY-ESO-1 T cell receptors (TCRs). A minimum dose of 0.1≤x<1 x 109 will be permitted. Patients receiving this low dose level will be evaluated separately for safety and efficacy.
Patients will undergo myeloma restaging approximately 1 week prior to the T cell infusion, and post infusion at days +28, +42 (week 6), +100 and 6 months post infusion and then every 3 months until relapse/progression or until 1 year, whenever comes first. At this point, patients will be followed semi-annually for up to 5 years and then annually for long term follow-up for monitoring for delayed adverse events until 15 years after receiving the genetically modified T cells, in accordance with FDA Guidelines.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Autologous genetically modified T cells | Experimental | Drug: Treatment with NY-ESO-1c259-modified T cellsPatients with a confirmed diagnosis of myeloma, with measurable disease, and who have received prior therapy for their myeloma that includes an IMiDs and a proteasome inhibitor and who have relapsed or progressive disease, will receive treatment with NY-ESO-1c259-modified T cells. An intended total dose of ≥0.1-1e10 total cells will be administered as a single infusion. A low dose infusion of 1e8 to < 1e9 will be allowed for patients if cells do not expand sufficiently to reach the target dose range. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 1. Written informed consent must be obtained from all patients before entry into the study
- 2. Patients must have a diagnosis of myeloma (see Appendix A for diagnostic criteria).
- 3. Patients must have progressive or active disease following prior therapy for their myeloma which:
- Patients who have failed second or third line therapy and beyond, such as DPACE, and who are experiencing a partial response rather than progressive disease are also eligible.
- 4. Patients must have measurable disease on study entry. Measurable disease may include quantifiable or detectable levels of serum or urine paraprotein. For patients with minimally secretory disease on study entry, serum free kappa or lambda light chain levels, or the serum free light chain ratio may be measured and used for disease monitoring if abnormal.
Key exclusion criteria (8 listed)
- 1. Pregnant or nursing females 2. HIV or HTLV-1/2 seropositivity 3. Known history of myelodysplasia 4. Known history of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy).
- 5. Active Infection with HBV or HCV
- 6. Prior allogeneic transplant 7. History of severe autoimmune disease requiring steroids or other immunosuppressive treatments.
- 8. Active immune-mediated diseases including: connective tissue diseases, uveitis, sarcoidosis, inflammatory bowel disease, multiple sclerosis.
- 9. Evidence or history of other significant cardiac, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease which would likely increase the risks of participating in the study. The specific type of stress test will be selected at the PI's discretion.
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 |
|---|---|---|
| Treatment with NY-ESO-1c259-modified T cellsAn intended total dose of ≥0.1-1e10 total cells will be administered as a single infusion. A low dose infusion of 1e8 to < 1e9 will be allowed for patients if cells do not expand sufficiently to reach the target dose range. For patients whose disease progresses and whose tumor still expresses tumor antigen and HLA-A201, a second infusion of up to 5e10 cells may be given. | Drug | Autologous genetically modified T cells |
Primary outcome
Adverse Events Related to Study Treatment
Time frame: Up to 12 months
Number of Participants with NCI CTCAE Version 4.0 Adverse Events related to study treatment greater than or equal to Grade 3
2 secondary outcomes
Evaluate the Direct Anti-tumor Activity of NY-ESO-1ᶜ²⁵⁹T
Time frame: 180 days
Peak Persistence of Modified T-cells in the Peripheral Blood
Time frame: Days 1, 3, 5, 8, 15, 22, 29, 43, 101, 130 181, every 3 months thereafter
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Edward Stadtmauer, MD study chair
University of Pennsylvania
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Treatment with NY-ESO-1c259-modified T cells in people with Multiple Myeloma, run by Adaptimmune at 2 sites 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 9 inclusion and 8 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 10 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 combined 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.
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 Jul 2018). 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?
Adverse Events Related to Study Treatment (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jan 2019.