Relapsed or Refractory Multiple MyelomaPhase 1NCT03464916
Study to Evaluate the Safety and Efficacy of Anti-CD38 CAR-T in Relapsed or Refractory Multiple Myeloma Patients
A Phase 1 study testing CAR2 Anti-CD38 A2 CAR-T Cells in people with Relapsed or Refractory Multiple Myeloma, run by Sorrento Therapeutics, Inc. at 4 sites in United States.
Trial summary
The study is an open-label Phase 1 single dose-escalation safety study of CAR2 Anti-CD38 A2 CAR-T Cells in patients with Relapsed or Refractory Multiple Myeloma, who meet all other eligibility criteria. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Multiple Myeloma
- What is being tested?
- CAR2 Anti-CD38 A2 CAR-T Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 4 sitesUnited States
- Study dates
- 15 Oct 2018to 28 Feb 2022
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient must either have relapsed refractory multiple myeloma (RRMM) after receiving prior lines of anti-myeloma treatments that included at least lenalidomide (Revlimid®), pomalidomide (Pomalyst®), bortezomib (Velcade®), carfilzomib (Kyprolis®), and daratumumab (Darzalex®) (refractory MM is defined as the development of disease progression during therapy with an anti-myeloma regimen or within 60 days of the last dose of an anti-myeloma regimen or the achievement of less than a partial response (PR) after greater than or equal to 2 cycles; for relapsing patients the duration from the last dose of the last prior treatment regimen to relapse must be less than or equal to 12 months); OR have multiple myeloma that is refractory to or has relapsed within 1 year of receiving high-dose therapy [HDT]/autologous stem cell transplantation [ASCT] in first- or second-line (refractory is defined as the achievement of less than a PR at the Day 90 to 100 post-ASCT response assessment)
- Must have measurable disease as defined by the following: Serum M-protein greater than or equal to 1 g/dL; OR Urine M-protein greater than or equal to 200 mg/24 hours; OR Serum free light chain (FLC) assay; involved FLC level greater than or equal to 10 mg/dL provided the serum FLC ratio is abnormal; OR greater than or equal to 30% clonal plasma cells in the bone marrow aspirate or biopsy sample
- Must have a life expectancy of at least 12 weeks
- Subjects should be willing and able to comply with the study schedule and protocols
- Females of childbearing potential must have 2 negative pregnancy tests, agree to ongoing pregnancy testing during the study, and sexually active female and male subjects must be willing to use an effective method to avoid pregnancies.
Who cannot join
- Subjects who received anticancer therapy or investigational drug within 28 days of first dose
- Subjects who received any approved anticancer chemotherapy within 21 days of first dose (exception cyclophosphamide as NMA conditioning)
- Subjects with unresolved toxicity greater than Grade 2 from previous therapies
- Have myeloma involvement of central nervous system (CNS) or a history of brain metastasis or spinal cord compression
- Subjects with an ECOG performance status greater than or equal to 3
- Has received allogenic hematopoietic stem cell transplantation (HSCT) within 6 months, have active graft-versus-host disease (GVHD) following transplant, or receiving immunosuppressive therapy following a transplant
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- Has received any CAR cell line therapies
- Has any clinically significant low baseline lab results for hemoglobin, platelet counts, and neutrophil counts, at screening unless resulting from underlying RRMM.
- Has any clinically significant elevated baseline lab results for serum creatinine, AST, and total bilirubin (except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome) at screening regardless of causality.
- Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C.
- Female subjects who are pregnant or breastfeeding
- Active bacterial, viral or fungal infections
- Has active plasma cell leukemia
- Has medical condition, abnormality, or psychiatric illness that would prevent study participation
- Left ventricular ejection fraction (LVEF) less than 40%
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Mayo Clinic Florida
Jacksonville, Florida, 32224
Icahn School of Medicine
New York, New York, 10029
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Mayo Clinic Minnesota
Rochester, Minnesota, 55905
About this study
Official title: A Phase 1, Open-Label, Dose-Escalation, Pharmacokinetic, and Pharmacodynamic Study of the Safety and Efficacy of CAR2 Anti-CD38 A2 CAR-T Cells in Patients With Relapsed or Refractory Multiple Myeloma
The study is an open-label Phase 1 single dose-escalation safety study of CAR2 Anti-CD38 A2 CAR-T Cells in patients with Relapsed or Refractory Multiple Myeloma, who meet all other eligibility criteria.
Read the detailed description
All subjects who received investigational CAR-T therapy will be included in the analyses and summaries of safety, efficacy, pharmacokinetic, and pharmacodynamic assessments.
- Conditions
- Relapsed or Refractory Multiple Myeloma
- Being tested
- CAR2 Anti-CD38 A2 CAR-T Cells
- Keywords
- CAR2 Anti-CD38 A2 CAR-T Cells
- Medical subject headings
- Recurrence, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR2 Anti-CD38 A2 CAR-T CellsBiological
Autologous IV infusion; dose-escalation
| Study group | Role | What they receive |
|---|---|---|
| CAR2 Anti-CD38 A2 CAR-T Cells | Experimental | Relapsed or Refractory Multiple Myeloma Receives: Biological: CAR2 Anti-CD38 A2 CAR-T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the MTD
The MTD is assessed according to a 3+3 dose-escalation design by the occurrence of treatment-emergent dose-limiting toxicities during the 28-day Treatment Period in the dose-escalation phase of the study
Measured: 28 days
Secondary outcomes (14)
Determine the CAR2 Anti-CD38 A2 CAR-T cell blood concentrations (Pharmacokinetic [PK] Profile) to evaluate the Cmax
CAR2 Anti-CD38 A2 CAR-T cell blood concentrations will be measured at different time points during the 28-day treatment period to evaluate the maximum concentration (Cmax).
Measured: 28 days
Determine the CAR2 Anti-CD38 A2 CAR-T cell blood concentrations (Pharmacokinetic [PK] Profile) to evaluate the AUC
CAR2 Anti-CD38 A2 CAR-T cell blood concentrations will be measured at different time points during the 28-day treatment period to evaluate the area under the curve (AUC).
Measured: 28 days
Evaluate the safety of Anti-CD38 A2 CAR-T cells in Patients with RRMM by incidence of treatment-emergent adverse events
The evaluation of safety will be measured by an assessment of the incidence of treatment-emergent adverse events for each patient in the dose-escalation and expansion phases of the study.
Measured: 6 months
Assess preliminary efficacy by response rate in accordance with the modified International Myeloma Working Group (IMWG) criteria
As a measure of activity, overall response rate will be assessed according to the modified International Myeloma Working Group (IMWG) criteria. Response will be assessed for each patient over a 6-month timeframe during both the dose-escalation and expansion phases of the protocol.
Measured: 6 months
Assess preliminary efficacy by depth of response in accordance with the modified International Myeloma Working Group (IMWG) criteria.
As a measure of activity, depth of response (ie, category of response) will be assessed according to the modified International Myeloma Working Group (IMWG) criteria. This will be assessed for each patient over a 6-month timeframe during both the dose-escalation and expansion phases of the protocol.
Measured: 6 months
Assess preliminary efficacy by duration of response in accordance with the modified International Myeloma Working Group (IMWG) criteria.
As a measure of activity, duration of response will be assessed according to the modified International Myeloma Working Group (IMWG) criteria. This will be assessed for each patient over a 6-month timeframe during both the dose-escalation and expansion phases of the protocol.
Measured: 6 months
Assess preliminary efficacy by progression-free survival.
As a measure of activity, Progression-free survival (PFS) will be assessed. The events for the assessment of PFS are disease progression and death events. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.
Measured: 6 months
Assess preliminary efficacy by overall survival.
As a measure of activity, Overall Survival (OS) will be assessed. The events for the assessment of OS are death events. Time to event endpoints will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.
Measured: 6 months
The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of treatment-emergent events.
The RP2D will be assessed by the incidence of treatment-emergent adverse events during the Treatment and Observation Periods.
Measured: 6 months
The determination of the recommended phase 2 dose will be based on an evaluation of overall response rate.
The rate of response as a determination factor for the RP2D will be assessed by the incidence of responses of at least partial response according to the IMWG criteria during the Treatment and Observation Periods.
Measured: 6 months
The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of depth of response.
The depth of response as a determination factor for the RP2D will be assessed by the IMWG categories for response according to changes from baseline in M-protein levels in serum and urine, per cent plasma cells in the bone marrow, and size (area) of soft tissue extramedullary plasmacytomas (if applicable). This will be assessed for each patient over a 6-month timeframe during both the dose-escalation and expansion phases of the protocol.
Measured: 6 months
The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of duration of response.
The duration of response as a determination factor for the RP2D will be assessed by the IMWG criteria for disease progression following the achievement of a response of at least a partial response according to changes in M-protein levels in serum and urine, per cent plasma cells in the bone marrow, the appearance of new lytic bone lesions, and/or the development of new soft tissue extramedullary plasmacytomas during the Treatment and Observation periods.
Measured: 6 months
The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of progression-free survival.
Progression-free survival as a determination factor for the RP2D will be assessed by the IMWG criteria for disease progression events and death events. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate. Progression-free survival will be evaluated during the Treatment and Observation Periods of the study.
Measured: 6 months
The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of overall survival.
Overall survival as a determination factor for the RP2D will be assessed by death events that occur during the Treatment and Observation Periods. Time- to-event endpoints will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2018
- Study start15 Oct 2018
- Primary completion23 Aug 2020
- Study completion28 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- To determine DLT and MTD, the design uses a 3+3 rule-based design. Dose escalation is permitted between successive cohorts based upon a specified algorithm, using discrete dosage steps.
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sorrento Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Edward Stadtmauer, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03464916
- Sponsor's protocol ID
- SOR-CART-MM-001
- Status last verified
- Mar 2022
- First submitted
- 14 Feb 2018
- Last updated
- 16 Mar 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Dose-Escalation, Pharmacokinetic, and Pharmacodynamic Study of the Safety and Efficacy of CAR2 Anti-CD38 A2 CAR-T Cells in Patients With Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT03464916
- Acronym / sponsor ID
- SOR-CART-MM-001
- Conditions
- Relapsed or Refractory Multiple Myeloma
- Keywords
- CAR2 Anti-CD38 A2 CAR-T Cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Sorrento Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Oct 2018 (actual)
- Primary completion
- 23 Aug 2020 (actual)
- Study completion
- 28 Feb 2022 (actual)
- First posted
- 14 Mar 2018 (actual)
- 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.
The study is an open-label Phase 1 single dose-escalation safety study of CAR2 Anti-CD38 A2 CAR-T Cells in patients with Relapsed or Refractory Multiple Myeloma, who meet all other eligibility criteria.
Detailed description
All subjects who received investigational CAR-T therapy will be included in the analyses and summaries of safety, efficacy, pharmacokinetic, and pharmacodynamic assessments.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- To determine DLT and MTD, the design uses a 3+3 rule-based design. Dose escalation is permitted between successive cohorts based upon a specified algorithm, using discrete dosage steps.
| Arm | Type | Receives |
|---|---|---|
| CAR2 Anti-CD38 A2 CAR-T Cells | Experimental | Biological: CAR2 Anti-CD38 A2 CAR-T CellsRelapsed or Refractory Multiple Myeloma |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- The patient must either have relapsed refractory multiple myeloma (RRMM) after receiving prior lines of anti-myeloma treatments that included at least lenalidomide (Revlimid®), pomalidomide (Pomalyst®), bortezomib (Velcade®), carfilzomib (Kyprolis®), and daratumumab (Darzalex®) (refractory MM is defined as the development of disease progression during therapy with an anti-myeloma regimen or within 60 days of the last dose of an anti-myeloma regimen or the achievement of less than a partial response (PR) after greater than or equal to 2 cycles; for relapsing patients the duration from the last dose of the last prior treatment regimen to relapse must be less than or equal to 12 months); OR have multiple myeloma that is refractory to or has relapsed within 1 year of receiving high-dose therapy [HDT]/autologous stem cell transplantation [ASCT] in first- or second-line (refractory is defined as the achievement of less than a PR at the Day 90 to 100 post-ASCT response assessment)
- Must have measurable disease as defined by the following: Serum M-protein greater than or equal to 1 g/dL; OR Urine M-protein greater than or equal to 200 mg/24 hours; OR Serum free light chain (FLC) assay; involved FLC level greater than or equal to 10 mg/dL provided the serum FLC ratio is abnormal; OR greater than or equal to 30% clonal plasma cells in the bone marrow aspirate or biopsy sample
- Must have a life expectancy of at least 12 weeks
- Subjects should be willing and able to comply with the study schedule and protocols
- Females of childbearing potential must have 2 negative pregnancy tests, agree to ongoing pregnancy testing during the study, and sexually active female and male subjects must be willing to use an effective method to avoid pregnancies.
Key exclusion criteria (15 listed)
- Subjects who received anticancer therapy or investigational drug within 28 days of first dose
- Subjects who received any approved anticancer chemotherapy within 21 days of first dose (exception cyclophosphamide as NMA conditioning)
- Subjects with unresolved toxicity greater than Grade 2 from previous therapies
- Have myeloma involvement of central nervous system (CNS) or a history of brain metastasis or spinal cord compression
- Subjects with an ECOG performance status greater than or equal to 3
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 |
|---|---|---|
| CAR2 Anti-CD38 A2 CAR-T CellsAutologous IV infusion; dose-escalation | Biological | CAR2 Anti-CD38 A2 CAR-T Cells |
Primary outcome
Determine the MTD
Time frame: 28 days
The MTD is assessed according to a 3+3 dose-escalation design by the occurrence of treatment-emergent dose-limiting toxicities during the 28-day Treatment Period in the dose-escalation phase of the study
14 secondary outcomes
Determine the CAR2 Anti-CD38 A2 CAR-T cell blood concentrations (Pharmacokinetic [PK] Profile) to evaluate the Cmax
Time frame: 28 days
Determine the CAR2 Anti-CD38 A2 CAR-T cell blood concentrations (Pharmacokinetic [PK] Profile) to evaluate the AUC
Time frame: 28 days
Evaluate the safety of Anti-CD38 A2 CAR-T cells in Patients with RRMM by incidence of treatment-emergent adverse events
Time frame: 6 months
Assess preliminary efficacy by response rate in accordance with the modified International Myeloma Working Group (IMWG) criteria
Time frame: 6 months
Assess preliminary efficacy by depth of response in accordance with the modified International Myeloma Working Group (IMWG) criteria.
Time frame: 6 months
Assess preliminary efficacy by duration of response in accordance with the modified International Myeloma Working Group (IMWG) criteria.
Time frame: 6 months
Assess preliminary efficacy by progression-free survival.
Time frame: 6 months
Assess preliminary efficacy by overall survival.
Time frame: 6 months
The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of treatment-emergent events.
Time frame: 6 months
The determination of the recommended phase 2 dose will be based on an evaluation of overall response rate.
Time frame: 6 months
The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of depth of response.
Time frame: 6 months
The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of duration of response.
Time frame: 6 months
The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of progression-free survival.
Time frame: 6 months
The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of overall survival.
Time frame: 6 months
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 16 Mar 2022.
- Individual participant dataSharing planned: No
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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 principal investigator
University of Pennsylvania
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CAR2 Anti-CD38 A2 CAR-T Cells in people with Relapsed or Refractory Multiple Myeloma, run by Sorrento Therapeutics, Inc. at 4 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 5 inclusion and 15 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 16 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 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?
Determine the MTD (time frame: 28 days). 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 16 Mar 2022.