Multiple MyelomaPhase 2NCT01352286
Redirected Auto T Cells for Advanced Myeloma
A Phase 2 study testing Autologous Genetically modified T cells in people with Multiple Myeloma, run by GlaxoSmithKline at 2 sites in United States.
Trial summary
The purpose of this study is to 1) evaluate the safety and tolerability of autologous genetically modified T cells transduced to express the high affinity NY-ESO-1c259 TCR in HLA-A2+ subjects and 2) measure the incidence of GVHD in patients following infusion of TCR modified autologous T cells. 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?
- Autologous Genetically modified T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 May 2011to 8 Jul 2019
- Phase
- Phase 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
- Myeloma has relapsed, progressed, or failed to respond after at least one prior course of therapy (consisting of at least 2 treatment cycles or months of therapy)
- Myeloma has responded partially to initial therapy but a complete response (immunofixation negative and normal serum free light chain) has NOT developed after a minimum of 3 cycles or months of initial therapy
- Myeloma has high-risk features as defined by the presence of one or more cytogenetic abnormalities known to confer a poor outcome even after standard auto-transplants: complex karyotype (≥ to 3 abnormalities), t(4;14), t(14;16), del (17) (p13.1), and/or chromosome 13 abnormalities. These patients may be enrolled even while in complete or near-complete remission
- Measurable disease on study entry, as defined by quantifiable or detectable levels of serum or urine paraprotein or elevated serum free light chains with abnormal ratio
- Patients who are in complete remission at the time of proposed study entry (serum and urine immunofixation consistently negative and normal serum free light chains) are not eligible unless their disease meets the criteria for high-risk as defined in protocol
- Ages 18-80
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- ECOG performance status 0-2 (unless due solely to bone pain)
- Prior to Lenalidomide maintenance phase, all study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®
- Females subjects of childbearing potential must have a negative pregnancy test and both male and female (of childbearing potential) subjects must agree to use reliable methods of contraception during the study.
- Lenalidomide treatment phase: able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin)
- HLA-A201 patients must have confirmed expression of NY-ESO-1 and/or LAGE. HLA-A2 patients must have the A-201 allele
- Adequate vital organ function as defined below:
- Serum creatinine ≤3.0 mg/dl and not on dialysis
- WBC at least 3000/mm³, platelet count at least 100,000/mm³
- SGOT ≤ to 2 x upper limit of normal and bilirubin ≤ to 2.0 mg/dl (unless due to Gilbert's syndrome)
- Left ventricular ejection fraction (LVEF) ≥ 45%. A lower LVEF is permissible if a formal cardiologic evaluation reveals no evidence for clinically significant functional impairment
- Adequate pulmonary function with mechanical parameters ≥ 40% predicted (FEV1, FVC, TLC, DLCO). Patients who are unable to complete PFTs due to bone pain or fracture must have a high resolution CT scan of the chest and must have acceptable arterial blood gases defined as a room air PO2 greater than 70 mmHg
- Patients should have recovered from any toxicities related to prior therapy or at least returned to their baseline level of organ function.
- Patients should be off of glucocorticoids for at least 2 weeks and/or other therapies for at least 1 week prior to enrollment
Who cannot join
- Pregnant or nursing females
- HIV or HTLV-1/2 seropositivity
- History of myelodysplasia
- History of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy)
- Active Hepatitis B (as defined by positive Hepatitis B surface antigen); positive Hepatitis C virus (HCV) antibody is NOT an exclusion
- Prior allogeneic transplant
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- History of severe autoimmune disease requiring steroids or other immunosuppressive treatments
- Active immune mediated diseases including: connective tissue diseases, uveitis, sarcoidosis, inflammatory bowel disease, multiple sclerosis
- 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
- Active bacterial, viral, or fungal infections
Trial locations and contacts
2 sites in 1 country.
United States2 sites
GSK Investigational Site
Baltimore, Maryland, 21201
GSK Investigational Site
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase I/IIa, Dual-cohort, Two-site, Clinical Trial Evaluating the Safety and Activity of Redirected Autologous T Cells Expressing a High Affinity TCR Specific for NY-ESO-1 Administered Post ASCT in Patients With Advanced Myeloma
The purpose of this study is to 1) evaluate the safety and tolerability of autologous genetically modified T cells transduced to express the high affinity NY-ESO-1c259 TCR in HLA-A2+ subjects and 2) measure the incidence of GVHD in patients following infusion of TCR modified autologous T cells.
Read the detailed description
The primary objective of this study is to evaluate the safety and tolerability of autologous genetically modified T cells. Genetic material is transferred into the subject's previously harvested autologous T cells to redirect them to target myeloma cells rather than their usual target. Study subjects must have systemic or multifocal myeloma requiring autologous stem cell transplantation whose disease has relapsed or incompletely responded to prior therapy or have high-risk features. Subjects must also have measureable disease on study entry, as defined by quantifiable or detectable levels of serum or urine paraprotein or elevated serum free light chains with an abnormal ratio.
- Conditions
- Multiple Myeloma
- Being tested
- Autologous Genetically modified T cells
- Keywords
- Multiple myeloma, Received initial treatment previously, Autologous stem cell transplantation
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Genetically modified T cellsGenetic
Patients will undergo myeloma restaging at days +42, +100, 6 months, 9 months and 1 year post infusion. At this point, in accordance with FDA Guidelines, all patients will enter long term follow up (LTFU) and be followed biannually for monitoring for gene transfer delayed adverse events until year 5 post infusion. From year 5, all patients will require annual LTFU visits for monitoring for delayed adverse events until year 15 after receiving the genetically modified T cells.
Patients whose disease progresses prior to year 1 will enter LTFU at time of progression; however these patients will be seen quarterly from progression until year 1 post infusion and then follow the LTFU schedule mentioned above.
| Study group | Role | What they receive |
|---|---|---|
| Autologous Genetically modified T cells | Experimental | Patients with advanced myeloma and who are candidates for autologous stem cell transplants, or syngeneic stem cell transplants (SSCT), will be eligible. Prior to full screening on this study, patients will undergo prescreening to evaluate HLA-A type and presence of NY-ESO-1c259T/LAGE antigen. Patients will undergo a steady-state mononuclear cell apheresis for T cell collection, with an optional second collection. Once mononuclear cells have been collected, patients (or donors in the case of SSCT) will then undergo hematopoietic stem cell mobilization. Patients will receive a dose >0.1-1 x 10¹º anti-CD3/anti-CD28-costimulated autologous T cells which have been genetically modified to express high affinity NY-ESO-1c259 TCRs. Receives: Genetic: Autologous Genetically 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 Adverse Events related to study treatment
Measured: Day -40 to Year 1 post-treatment
Secondary outcomes (6)
Number of Participants With Response Per International Myeloma Working Group (IMWG) 2011 Criteria
Objective Response Rate (ORR) of sCR (stringent complete response), CR (complete response), VGPR (very good partial response), PR (partial response)
Measured: Change from Baseline at Day 42, 100, 180, 270 and Year 1
Best Objective Response (BOR)
Number of participants with Best Objective Response of sCR, CR, VGPR, or PR
Measured: Best Objective Response prior to initiation of lenalidomide and at Year 1
Duration of Response (DOR), Progression Free Survival (PFS), Overall Survival (OS)
Calculated median DOR, PFS, OS
Measured: DOR: Initial date of response to date of progressive disease or death PFS: Date of first T -cell infusion to earliest date of disease progression of death due to any cause OS: Date of first T-cell infusion to date of death from any cause.
Peak Persistence of Modified T-cells in the Peripheral Blood
Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood
Measured: Post-infusion through Day 42
Marrow Antigen Expression Pre-and Post-infusion
Number of participants with NY-ESO-1 and LAGE or LAGE-1a expression in the marrow post-infusion
Measured: Pre- and post-infusion
Engraftment of Gene-modified Pentamer+ CD4+ T Cells and CD8+ T Cells
Number of participants with engraftment in blood and bone marrow
Measured: Post Treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2011 (estimated)
- Study start13 May 2011
- Primary completion25 Aug 2017
- Study completion8 Jul 2019
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01352286
- Sponsor's protocol ID
- 209393
- Other IDs
- ADP 01411
- Status last verified
- Nov 2019
- First submitted
- 4 May 2011
- Last updated
- 3 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Stadtmauer EA, Faitg TH, Lowther DE, Badros AZ, Chagin K, Dengel K, Iyengar M, Melchiori L, Navenot JM, Norry E, Trivedi T, Wang R, Binder GK, Amado R, Rapoport AP. Long-term safety and activity of NY-ESO-1 SPEAR T cells after autologous stem cell transplant for myeloma. Blood Adv. 2019 Jul 9;3(13):2022-2034. doi: 10.1182/bloodadvances.2019000194.
PubMed 31289029
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa, Dual-cohort, Two-site, Clinical Trial Evaluating the Safety and Activity of Redirected Autologous T Cells Expressing a High Affinity TCR Specific for NY-ESO-1 Administered Post ASCT in Patients With Advanced Myeloma
- ClinicalTrials.gov ID
- NCT01352286
- Acronym / sponsor ID
- 209393
- Conditions
- Multiple Myeloma
- Keywords
- Multiple myeloma, Received initial treatment previously, Autologous stem cell transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 13 May 2011 (actual)
- Primary completion
- 25 Aug 2017 (actual)
- Study completion
- 8 Jul 2019 (actual)
- First posted
- 11 May 2011 (estimated)
- Results
- Posted 3 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to 1) evaluate the safety and tolerability of autologous genetically modified T cells transduced to express the high affinity NY-ESO-1c259 TCR in HLA-A2+ subjects and 2) measure the incidence of GVHD in patients following infusion of TCR modified autologous T cells.
Detailed description
The primary objective of this study is to evaluate the safety and tolerability of autologous genetically modified T cells. Genetic material is transferred into the subject's previously harvested autologous T cells to redirect them to target myeloma cells rather than their usual target. Study subjects must have systemic or multifocal myeloma requiring autologous stem cell transplantation whose disease has relapsed or incompletely responded to prior therapy or have high-risk features. Subjects must also have measureable disease on study entry, as defined by quantifiable or detectable levels of serum or urine paraprotein or elevated serum free light chains with an abnormal ratio.
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 | Genetic: Autologous Genetically modified T cellsPatients with advanced myeloma and who are candidates for autologous stem cell transplants, or syngeneic stem cell transplants (SSCT), will be eligible. Prior to full screening on this study, patients will undergo prescreening to evaluate HLA-A type and presence of NY-ESO-1c259T/LAGE antigen. Patients will undergo a steady-state mononuclear cell apheresis for T cell collection, with an optional second collection. Once mononuclear cells have been collected, patients (or donors in the case of SSCT) will then undergo hematopoietic stem cell mobilization. Patients will receive a dose >0.1-1 x 10¹º anti-CD3/anti-CD28-costimulated autologous T cells which have been genetically modified to express high affinity NY-ESO-1c259 TCRs. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Myeloma has relapsed, progressed, or failed to respond after at least one prior course of therapy (consisting of at least 2 treatment cycles or months of therapy)
- Myeloma has responded partially to initial therapy but a complete response (immunofixation negative and normal serum free light chain) has NOT developed after a minimum of 3 cycles or months of initial therapy
- Myeloma has high-risk features as defined by the presence of one or more cytogenetic abnormalities known to confer a poor outcome even after standard auto-transplants: complex karyotype (≥ to 3 abnormalities), t(4;14), t(14;16), del (17) (p13.1), and/or chromosome 13 abnormalities. These patients may be enrolled even while in complete or near-complete remission
- Measurable disease on study entry, as defined by quantifiable or detectable levels of serum or urine paraprotein or elevated serum free light chains with abnormal ratio
- Patients who are in complete remission at the time of proposed study entry (serum and urine immunofixation consistently negative and normal serum free light chains) are not eligible unless their disease meets the criteria for high-risk as defined in protocol
Key exclusion criteria (10 listed)
- Pregnant or nursing females
- HIV or HTLV-1/2 seropositivity
- History of myelodysplasia
- History of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy)
- Active Hepatitis B (as defined by positive Hepatitis B surface antigen); positive Hepatitis C virus (HCV) antibody is NOT an exclusion
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 |
|---|---|---|
| Autologous Genetically modified T cellsPatients will undergo myeloma restaging at days +42, +100, 6 months, 9 months and 1 year post infusion. At this point, in accordance with FDA Guidelines, all patients will enter long term follow up (LTFU) and be followed biannually for monitoring for gene transfer delayed adverse events until year 5 post infusion. From year 5, all patients will require annual LTFU visits for monitoring for delayed adverse events until year 15 after receiving the genetically modified T cells. Patients whose disease progresses prior to year 1 will enter LTFU at time of progression; however these patients will be seen quarterly from progression until year 1 post infusion and then follow the LTFU schedule mentioned above. | Genetic | Autologous Genetically modified T cells |
Primary outcome
Adverse Events Related to Study Treatment
Time frame: Day -40 to Year 1 post-treatment
Number of Participants with Adverse Events related to study treatment
6 secondary outcomes
Number of Participants With Response Per International Myeloma Working Group (IMWG) 2011 Criteria
Time frame: Change from Baseline at Day 42, 100, 180, 270 and Year 1
Best Objective Response (BOR)
Time frame: Best Objective Response prior to initiation of lenalidomide and at Year 1
Duration of Response (DOR), Progression Free Survival (PFS), Overall Survival (OS)
Time frame: DOR: Initial date of response to date of progressive disease or death PFS: Date of first T -cell infusion to earliest date of disease progression of death due to any cause OS: Date of first T-cell infusion to date of death from any cause.
Peak Persistence of Modified T-cells in the Peripheral Blood
Time frame: Post-infusion through Day 42
Marrow Antigen Expression Pre-and Post-infusion
Time frame: Pre- and post-infusion
Engraftment of Gene-modified Pentamer+ CD4+ T Cells and CD8+ T Cells
Time frame: Post Treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31289029Stadtmauer EA, Faitg TH, Lowther DE, Badros AZ, Chagin K, Dengel K, Iyengar M, Melchiori L, Navenot JM, Norry E, Trivedi T, Wang R, Binder GK, Amado R, Rapoport AP. Long-term safety and activity of NY-ESO-1 SPEAR T cells after autologous stem cell transplant for myeloma. Blood Adv. 2019 Jul 9;3(13):2022-2034. doi: 10.1182/bloodadvances.2019000194.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Autologous Genetically modified T cells in people with Multiple Myeloma, run by GlaxoSmithKline 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 19 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: finished, as of the sponsor's last update on 3 Dec 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 phase mean?
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 3 Jan 2019). 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: Day -40 to Year 1 post-treatment). 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 NCT01352286, 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 3 Dec 2019.