Multiple MyelomaPhase 1/2EVOLVENCT03430011
Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma
A Phase 1/2 study testing JCARH125 and JCARH125 + anakinra in people with Multiple Myeloma, run by Juno Therapeutics, a Subsidiary of Celgene at 20 sites in United States.
Trial summary
This is an open-label, multicenter, Phase 1/2 study to determine the safety and efficacy of JCARH125, a CAR T-cell product that targets B-cell maturation antigen (BCMA), in adult subjects with relapsed and/or refractory multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- JCARH125 and JCARH125 + anakinra
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 165 participants
- Where
- 20 sitesUnited States
- Study dates
- 1 Feb 2018to 30 Mar 2023
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of multiple myeloma (MM) with relapsed and/or refractory (R/R) disease. Participants must have received at least 3 prior anti-myeloma treatment regimens. Participants must have previously received all of the following therapies and must be refractory to the last line of therapy prior to entering the study (not applicable to Phase 2a):
- Autologous stem cell transplant
- A regimen that included an immunomodulatory agent (eg, thalidomide, lenalidomide, pomalidomide) and a proteasome inhibitor (eg, bortezomib, carfilzomib, ixazomib), either alone or in combination
- Anti-CD38 (eg, daratumumab) as part of a combination regimen or as a monotherapy
- Subjects who have received prior allogeneic stem cell transplant or donor lymphocyte infusion at least 100 days before enrollment with no signs of acute or chronic graft-versus-host disease (GVHD) will be considered eligible. Subjects who were not candidates to receive one or more of the above treatments (ie, contraindicated) are eligible.
- Subjects must have measurable disease.
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- Subject must be willing to provide fresh bone marrow biopsy samples during Screening (and prior to study treatment, if required).
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Adequate renal, bone marrow, hepatic, pulmonary, and cardiac function
- Phase 2a cohorts only - Subjects with R/R MM who have been previously treated with prior BCMA-directed anti-myeloma therapy, achieved at least a partial response (PR) and progressed on the following treatment:
- Subjects who have received prior BCMA-directed CAR T-cell therapy. The last CAR T-cell therapy must have been received at least 6 months prior to JCARH125 screening.
- Subjects who have received prior BCMA-directed T-cell engager therapy.
- Subjects who have received prior BCMA-directed antibody-drug conjugate therapy.
Who cannot join
- Subjects with known active or history of CNS involvement by malignancy
- Subjects with solitary plasmacytoma; active or history of plasma cell leukemia (PCL); Waldenstrom's macroglobulinemia; Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasmaproliferative disorder, Skin changes (POEMS) syndrome; or symptomatic amyloidosis
- Subjects who are considered eligible to receive and have not refused an autologous stem cell transplant
- History of another primary malignancy that has not been in remission for at least 3 years. The following are exempt from the 3-year limit: non-melanoma skin cancer, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, and in situ breast cancer that has been completely resected.
- Require systemic immunosuppressive therapies (eg, calcineurin inhibitors, methotrexate, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-IL-6 or anti-IL-6 receptor [IL-6R])
- Prior CAR T-cell or other genetically-modified T-cell therapy (not applicable for subjects enrolled in Phase 2a cohorts)
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- Prior treatment with a BCMA-targeted agent (not applicable for subjects enrolled in Phase 2a cohorts)
- History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
- Untreated or active infection at time of initial screening, at the time of leukapheresis, within 72 hrs before lymphodepletion, or 5 days before JCARH125 infusion.
- History of any of the following cardiovascular conditions within 6 months of screening: Class III or IV heart failure as defined by the New York Heart Association (NYHA), myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmias, or other clinically significant cardiac disease
- Subjects with known hypersensitivity to E Coli-derived proteins (only applicable to subjects in Phase 1 Anakinra Cohort)
- History of severe immediate hypersensitivity reaction to any of the protocol-mandated or recommended agents used in this study
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
United States20 sites
Local Institution - 0042
Atlanta, Georgia, 30322
Local Institution - 0009
Baltimore, Maryland, 21231
Local Institution - 0006
Birmingham, Alabama, 10016
Local Institution - 0005
Boston, Massachusetts, 02114
Local Institution - 0013
Buffalo, New York, 14263
Local Institution - 0060
Denver, Colorado, 80218
Local Institution - 0062
Detroit, Michigan, 48201
Local Institution - 0007
Duarte, California, 91010
Local Institution - 0038
Hackensack, New Jersey, 07601
Local Institution - 0061
Indianapolis, Indiana, 46202
Local Institution - 0059
Los Angeles, California, 90095-1678
Local Institution - 0055
Milwaukee, Wisconsin, 53226
Local Institution - 0016
New Lenox, Illinois, 60451
Local Institution - 0001
New York, New York, 10065
Local Institution - 0058
Portland, Oregon, 97201-3098
Local Institution - 0054
Rochester, Minnesota, 55905
Local Institution - 0010
San Francisco, California, 94158
Local Institution - 0023
Seattle, Washington, 98104
Local Institution - 0018
Seattle, Washington, 98109
Local Institution - 0053
Westwood, Kansas, 66205
About this study
Official title: Protocol H125001: An Open-Label Phase 1/2 Study of JCARH125, BCMA-targeted Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed or Refractory Multiple Myeloma
This is an open-label, multicenter, Phase 1/2 study to determine the safety and efficacy of JCARH125, a CAR T-cell product that targets B-cell maturation antigen (BCMA), in adult subjects with relapsed and/or refractory multiple myeloma. The study will include a Phase 1 part to determine the recommended dose of JCARH125 in subjects with relapsed and/or refractory multiple myeloma, followed by a Phase 2 part to further evaluate the safety and efficacy of JCARH125 at the recommended dose. The safety and tolerability of JCARH125 in subjects who receive prophylactic treatment with anakinra will be evaluated in a separate Phase 1 cohort. The antitumor activity of JCARH125 in subjects who have been previously treated with BCMA-directed therapy will be evaluated in separate Phase 2a cohorts.
- Conditions
- Multiple Myeloma
- Being tested
- JCARH125, JCARH125 + anakinra
- Keywords
- JCARH125, chimeric antigen receptor, multiple myeloma, CAR T cells, B-cell maturation antigen, BCMA, autologous T-cell therapy, immunotherapy
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JCARH125Biological
Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCARH125. During JCARH125 production, participants may receive bridging chemotherapy for disease control. Following successful generation of JCARH125 product, participants will receive a course of lymphodepleting chemotherapy followed by one dose of JCARH125 administered intravenously (IV).
JCARH125 + anakinraBiological
Participants will undergo leukapheresis to isolate PBMCs for the production of JCARH125. During JCARH125 production, participants may receive bridging chemotherapy for disease control. Following successful generation of JCARH125 product, participants will receive a course of lymphodepleting chemotherapy followed by two doses of anakinra administered subcutaneously and one dose of JCARH125 administered IV. Subjects receive anakinra for 5 consecutive days following JCARH125 infusion.
| Study group | Role | What they receive |
|---|---|---|
| JCARH125 | Experimental | Subjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by a single dose of JCARH125 Receives: Biological: JCARH125 |
| JCARH125 + anakinra | Experimental | Subjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by prophylactic treatment with anakinra and a single dose of JCARH125 Receives: Biological: JCARH125 + anakinra |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-Limiting Toxicity (DLT) in Phase 1
DLT is defined as adverse events (AEs) that occur within 21 days following JCARH125 infusion and meet any of the following criteria:
- Treatment-emergent Grade ≥3 allergic reactions related to JCARH125;
- Treatment-emergent Grade 3 seizures, regardless of attribution, that do not resolve to Grade ≤2 within 3 days in participants who have no evidence of central nervous system (CNS) involvement of Multiple Myeloma or other CNS pathology;
- Treatment-emergent autoimmune toxicity Grade ≥3, regardless of attribution (excluding B-cell aplasia);
- Treatment-emergent Grade 3 CRS that does not resolve to Grade ≤2 within 72 hours;
- Any other treatment-emergent Grade 3 AE related to JCARH125 that does not resolve to Grade ≤2 within 7 days;
- Any treatment-emergent Grade 4 AE related to JCARH125 that does not resolve to Grade ≤2 within 7 days;
- Treatment-emergent Grade 4 Cytokine Release Syndrome of any duration;
- Any treatment-emergent Grade 5 toxicity not due to the underlying malignancy
Measured: From day 1 to day 22 following JCARH125 infusion (Up to 21 days)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity in Phase 1 and Phase 1 Anakinra
TEAE is defined as an AE that starts any time from initiation of JCARH125 administration through and including 90 days following the JCARH125 infusion graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Any AE occurring after the initiation of another anticancer treatment will not be considered a TEAE. Grade 3=Severe; Grade 4=Life-threatening; and Grade 5=death.
Measured: From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)
Number of Participants With Clinically Significant Laboratory Abnormalities by Severity in Phase 1 and Phase 1 Anakinra
Clinically significant laboratory abnormalities are assessed by investigator and are reported as treatment-emergent adverse event (TEAE). TEAE is defined as an AE that starts any time from initiation of JCARH125 administration through and including 90 days following the JCARH125 infusion graded by Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Any AE occurring after the initiation of another anticancer treatment is not considered a TEAE. Grade 3=Severe; Grade 4=Life-threatening.
Measured: From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)
Number of Participants Receiving Prophylactic Anakinra With Grade ≥2 Cytokine Release Syndrome (CRS) in Phase 1 and Phase 1 Anakinra
Number of participants receiving prophylactic anakinra with grade ≥ 2 CRS relative to the number of participants treated at the recommended Phase 2 dose (RP2D) in the Phase 1 dose escalation portion of the trial with grade ≥ 2 CRS. CRS grade is defined by the most severe symptom (excluding fever). Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening
Measured: From first infusion to up to aproximately 61 months
Time to Onset of Grade ≥2 Cytokine Release Syndrome (CRS) in Phase 1 and Phase 1 Anakinra
Time to first onset of Grade ≥2 CRS in participants receiving prophylactic anakinra relative to onset of Grade ≥ 2 CRS in participants treated at the RP2D(s) in the Phase 1 dose escalation portion of the trial. Time to onset is calculated from the latest JCARH125 infusion prior to the first onset of Grade >= 2 CRS. CRS grade is defined by the most severe symptom (excluding fever). Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening
Measured: From JCARH125 infusion to the first onset of Grade ≥2 CRS (Up to approximately 61 months)
Number of Participants Receiving Prophylactic Anakinra With no Cytokine Release Syndrome (CRS) Occurring on Days 1-3 in Phase 1 Anakinra
The number of participants receiving prophylactic anakinra with no CRS occurring on study days 1, 2, or 3. CRS grade is defined by the most severe symptom (excluding fever). Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening
Measured: Day 1, 2, 3
Overall Response Rate (ORR) in Phase 2 and Phase 2a
ORR is defined as stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR), according to IMWG criteria. Participants without any reported disease response assessments will be considered non-responders.
sCR=complete response plus normal free light chain ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR=negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates. When the only method to measure disease is by serum FLC levels, CR can be defined as a normal FLC ratio of 0.26 to 1.65; VGPR=serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein level plus urine M-protein level < 100 mg/24 h; PR=≥ 50% reduction of serum M protein plus reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg/24 h
Measured: From the time of the JCARH125 infusion until disease progression, end of study, or the start of another anticancer therapy or stem cell transplant (Up to aproximately 61 months)
Secondary outcomes (19)
Maximum Observed Concentration (Cmax)
Cmax is the maximal concentration of JCARH125 CAR T cells in the blood after its infusion as determined by quantitative polymerase chain reaction (qPCR) to detect the JCARH125 transgene.
Measured: From JCARH125 infusion through the day 29 visit
Time to Maximum Observed Concentration (Tmax)
Tmax is the first study day the maximum observed concetration (Cmax) of JCARH125 CAR T cells in the blood is reached as determined by quantitative polymerase chain reaction (qPCR) to detect the JCARH125 transgene.
Measured: From JCARH125 infusion through the day 29 visit
Area Under the Concertation-Time Curve (AUC) From Time Day 1 to Day 29 [AUC (0-28 Days)]
AUC (0-28) of JCARH125 CAR T cells in the blood as determined by quantitative polymerase chain reaction (qPCR) to detect the JCARH125 transgene.
Measured: From JCARH125 infusion through 28 days after the infusion
Number of Participants With Pharmacokinetics Persistence
Pharmacokinetics persistence of JCARH125 CAR T cells in the blood as determined by quantitative polymerase chain reaction (qPCR) over time to detect the JCARH125 transgene. Persistence is defined as a transgene count greater than or equal to the lower limit of detection (LLOD).
Measured: Day 29, 60, 90, 180, 270, 365, 545, 730
Overall Response Rate (ORR) in Phase 1 and Phase 1 Anakinra
ORR is defined as stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR), according to IMWG criteria. Participants without any reported disease response assessments will be considered non-responders.
sCR=complete response plus normal free light chain ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR=negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates. When the only method to measure disease is by serum FLC levels, CR can be defined as a normal FLC ratio of 0.26 to 1.65; VGPR=serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein level plus urine M-protein level < 100 mg/24 h; PR=≥ 50% reduction of serum M protein plus reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg/24 h
Measured: From the time of the JCARH125 infusion until disease progression, end of study, or the start of another anticancer therapy or stem cell transplant (Up to 61 approximately months)
Complete Response Rate (CRR)
CRR is defined as stringent complete response (sCR) or complete response (CR), according to IMWG criteria. Participants without any reported disease response assessments will be considered non-responders.
sCR=complete response plus normal free light chain ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR=negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates
Measured: From the time of the JCARH125 infusion until disease progression, end of study, or the start of another anticancer therapy or stem cell transplant (Up to aproximately 61 months)
Duration of Response (DoR) in Phase 2 and 2a
DoR is defined as the time from first response (stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR)) to the earlier date of progressive disease or death due to any cause.
sCR=complete response plus normal free light chain ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR=negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates; VGPR=serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein level plus urine M-protein level < 100 mg/24 h; PR=≥ 50% reduction of serum M protein plus reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg/24 h.
Progressive disease is defined as (1) Increase of ≥25% from lowest confirmed response; (2) Appearance of a new lesion(s); (3) ≥50% increase in circulating plasma cells.
Measured: From first response to the date of progression or death due to any cause, whichever occurs first (Up to approixmately 61 months)
Duration of Complete Response (DoCR) in Phase 2 and 2a
DoCR is defined as the time from first response (stringent complete response (sCR), complete response (CR)) to the earlier date of progressive disease or death due to any cause.
sCR=complete response plus normal free light chain ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR=negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates.
Progressive disease is defined as (1) Increase of ≥25% from lowest confirmed response; (2) Appearance of a new lesion(s); (3) ≥50% increase in circulating plasma cells.
Measured: From first response to the date of progression or death due to any cause, whichever occurs first (Up to approixmately 61 months)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity in Phase 2 and Phase 2a
TEAE is defined as an AE that starts any time from initiation of JCARH125 administration through and including 90 days following the JCARH125 infusion graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Any AE occurring after the initiation of another anticancer treatment will not be considered a TEAE. Grade 3=Severe; Grade 4=Life-threatening; and Grade 5=death.
Measured: From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)
Number of Participants With Clinically Significant Laboratory Abnormalities by Severity in Phase 2 and Phase 2a
Clinically significant laboratory abnormalities are assessed by investigator and are reported as treatment-emergent adverse event (TEAE). TEAE is defined as an AE that starts any time from initiation of JCARH125 administration through and including 90 days following the JCARH125 infusion graded by Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Any AE occurring after the initiation of another anticancer treatment is not considered a TEAE. Grade 3=Severe; Grade 4=Life-threatening.
Measured: From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)
Overall Survival (OS) in Phase 2 and Phase 2a
OS is defined as the time from the JCARH125 infusion until death due to any cause.
Measured: Form date of first infusion to the date of death due to any reason (Up to apprixamtely 61 months)
Progression Free Survival (PFS) in Phase 2 and Phase 2a
PFS is defined as the time from JCARH125 infusion until the earliest date of disease progression or death from any cause. Progressive disease (PD) is defined as (1) Increase of ≥25% from lowest confirmed response in one or more of the following: Serum M-protein absolute increase ≥0.5 g/dL; Serum M-protein increase ≥1 g/dL, if the lowest M component was ≥5 g/dL; Urine M protein absolute increase ≥200 mg/24 h; the difference between involved and uninvolved FLC levels absolute increase >10 mg/dL; Bone marrow plasma-cell percentage irrespective of baseline status absolute increase ≥10%. (2) Appearance of a new lesion(s), ≥50% increase from nadir in SPDd of >1 lesion, or ≥50% increase in the longest diameter of a previous lesion >1 cm in short axis. (3) ≥50% increase in circulating plasma cells (minimum of 200 cells μL) if this is the only measure of disease.
Measured: Form date of first infusion to the date of disease progression, or death, due to any reason (Up to approximately 61 months)
Time to Response (TTR) in Phase 2 and Phase 2a
TTR is defined from JCARH125 infusion to the first document of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).
sCR=complete response plus normal free light chain ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR=negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates; VGPR=serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein level plus urine M-protein level < 100 mg/24 h; PR=≥ 50% reduction of serum M protein plus reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg/24 h.
Progressive disease is defined as (1) Increase of ≥25% from lowest confirmed response; (2) Appearance of a new lesion(s); (3) ≥50% increase in circulating plasma cells.
Measured: Form date of first infusion to the date of disease progression, or death, due to any reason (Up to approximately 61 months)
Time to Complete Response (TTCR) in Phase 2 and Phase 2a
TTCR is defined from JCARH125 infusion to the first document of stringent complete response (sCR) or complete response (CR).
sCR=complete response plus normal free light chain ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR=negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates.
Progressive disease is defined as (1) Increase of ≥25% from lowest confirmed response; (2) Appearance of a new lesion(s); (3) ≥50% increase in circulating plasma cells.
Measured: Form date of first infusion to the date of disease progression, or death, due to any reason (Up to approximately 61 months)
Change From Baseline in the Total Score of European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) in Phase 2
The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures such as functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Subscale scores are transformed to 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. Baseline is defined as the last non-missing measurement prior to JCARH125 infusion.
Measured: Baseline and visit 24 month
Change From Baseline in the Total Score of European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ-MY20) in Phase 2
QLQ-MY20 includes 20 questions across four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the disease symptoms scale = higher level of symptomatology.
Measured: Baseline and visit 24 month
Change From Baseline (EQ-5D-5L) Index Score in Phase 2
EQ-5D-5L is a standardized measure of health status that consists of descriptive system and Visual Analogue scale VAS). The descriptive system comprises dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the dimensions are combined in a 5-digit number corresponding to response categories for successive dimensions using a scoring algorithm. The VAS system has endpoints labeled "the best health you can imagine" and "the worst health you can imagine." The scale is numbered from 0 to 100 with 0 corresponding to the worst imaginable health state and 100 corresponding to the best imaginable health state. A high score represents a better level of quality of life
Measured: Baseline and visit 24 month
Duration of Hospitalization From JCARH125 Administration in Phase 2
Total length of all intensive care unit (ICU) and non-ICU stays from JCARH125 Administration. ICU inpatient and non-ICU inpatient are not exclusive. Total length includes participants who had multiple hospitalization stays.
Measured: From JCARH125 infusion to up to approximately 61 months
Reasons for Hospitalization From JCARH125 Administration in Phase 2
Number of participants with reasons for hospitalization from JCARH125 administration
Measured: From JCARH125 infusion to up to approximately 61 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2018
- Study start1 Feb 2018
- Primary completion30 Mar 2023
- Study completion30 Mar 2023
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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- Juno Therapeutics, a Subsidiary of Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03430011
- Sponsor's protocol ID
- H125001
- Acronym
- EVOLVE
- Status last verified
- Apr 2024
- First submitted
- 6 Feb 2018
- Last updated
- 24 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protocol H125001: An Open-Label Phase 1/2 Study of JCARH125, BCMA-targeted Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT03430011
- Acronym / sponsor ID
- EVOLVE / H125001
- Conditions
- Multiple Myeloma
- Keywords
- JCARH125, chimeric antigen receptor, multiple myeloma, CAR T cells, B-cell maturation antigen, BCMA, autologous T-cell therapy, immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 165 participants (actual)
- Lead sponsor
- Juno Therapeutics, a Subsidiary of CelgeneIndustry (pharma, biotech, devices)
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 30 Mar 2023 (actual)
- Study completion
- 30 Mar 2023 (actual)
- First posted
- 12 Feb 2018 (actual)
- Results
- Posted 24 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, multicenter, Phase 1/2 study to determine the safety and efficacy of JCARH125, a CAR T-cell product that targets B-cell maturation antigen (BCMA), in adult subjects with relapsed and/or refractory multiple myeloma. The study will include a Phase 1 part to determine the recommended dose of JCARH125 in subjects with relapsed and/or refractory multiple myeloma, followed by a Phase 2 part to further evaluate the safety and efficacy of JCARH125 at the recommended dose. The safety and tolerability of JCARH125 in subjects who receive prophylactic treatment with anakinra will be evaluated in a separate Phase 1 cohort. The antitumor activity of JCARH125 in subjects who have been previously treated with BCMA-directed therapy will be evaluated in separate Phase 2a cohorts.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| JCARH125 | Experimental | Biological: JCARH125Subjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by a single dose of JCARH125 |
| JCARH125 + anakinra | Experimental | Biological: JCARH125 + anakinraSubjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by prophylactic treatment with anakinra and a single dose of JCARH125 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Diagnosis of multiple myeloma (MM) with relapsed and/or refractory (R/R) disease. Participants must have received at least 3 prior anti-myeloma treatment regimens. Participants must have previously received all of the following therapies and must be refractory to the last line of therapy prior to entering the study (not applicable to Phase 2a):
- Subjects who have received prior allogeneic stem cell transplant or donor lymphocyte infusion at least 100 days before enrollment with no signs of acute or chronic graft-versus-host disease (GVHD) will be considered eligible. Subjects who were not candidates to receive one or more of the above treatments (ie, contraindicated) are eligible.
- Subjects must have measurable disease.
- Subject must be willing to provide fresh bone marrow biopsy samples during Screening (and prior to study treatment, if required).
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Key exclusion criteria (12 listed)
- Subjects with known active or history of CNS involvement by malignancy
- Subjects with solitary plasmacytoma; active or history of plasma cell leukemia (PCL); Waldenstrom's macroglobulinemia; Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasmaproliferative disorder, Skin changes (POEMS) syndrome; or symptomatic amyloidosis
- Subjects who are considered eligible to receive and have not refused an autologous stem cell transplant
- History of another primary malignancy that has not been in remission for at least 3 years. The following are exempt from the 3-year limit: non-melanoma skin cancer, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, and in situ breast cancer that has been completely resected.
- Require systemic immunosuppressive therapies (eg, calcineurin inhibitors, methotrexate, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-IL-6 or anti-IL-6 receptor [IL-6R])
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 |
|---|---|---|
| JCARH125Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCARH125. During JCARH125 production, participants may receive bridging chemotherapy for disease control. Following successful generation of JCARH125 product, participants will receive a course of lymphodepleting chemotherapy followed by one dose of JCARH125 administered intravenously (IV). | Biological | JCARH125 |
| JCARH125 + anakinraParticipants will undergo leukapheresis to isolate PBMCs for the production of JCARH125. During JCARH125 production, participants may receive bridging chemotherapy for disease control. Following successful generation of JCARH125 product, participants will receive a course of lymphodepleting chemotherapy followed by two doses of anakinra administered subcutaneously and one dose of JCARH125 administered IV. Subjects receive anakinra for 5 consecutive days following JCARH125 infusion. | Biological | JCARH125 + anakinra |
Primary outcome
Number of Participants With Dose-Limiting Toxicity (DLT) in Phase 1
Time frame: From day 1 to day 22 following JCARH125 infusion (Up to 21 days)
DLT is defined as adverse events (AEs) that occur within 21 days following JCARH125 infusion and meet any of the following criteria: * Treatment-emergent Grade ≥3 allergic reactions related to JCARH125; * Treatment-emergent Grade 3 seizures, regardless of attribution, that do not resolve to Grade ≤2 within 3 days in participants who have no evidence of central nervous system (CNS) involvement of Multiple Myeloma or other CNS pathology; * Treatment-emergent autoimmune toxicity Grade ≥3, regardless of attribution (excluding B-cell aplasia); * Treatment-emergent Grade 3 CRS that does not resolve to Grade ≤2 within 72 hours; * Any other treatment-emergent Grade 3 AE related to JCARH125 that does not resolve to Grade ≤2 within 7 days; * Any treatment-emergent Grade 4 AE related to JCARH125 that does not resolve to Grade ≤2 within 7 days; * Treatment-emergent Grade 4 Cytokine Release Syndrome of any duration; * Any treatment-emergent Grade 5 toxicity not due to the underlying malignancy
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity in Phase 1 and Phase 1 Anakinra
Time frame: From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)
TEAE is defined as an AE that starts any time from initiation of JCARH125 administration through and including 90 days following the JCARH125 infusion graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Any AE occurring after the initiation of another anticancer treatment will not be considered a TEAE. Grade 3=Severe; Grade 4=Life-threatening; and Grade 5=death.
Number of Participants With Clinically Significant Laboratory Abnormalities by Severity in Phase 1 and Phase 1 Anakinra
Time frame: From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)
Clinically significant laboratory abnormalities are assessed by investigator and are reported as treatment-emergent adverse event (TEAE). TEAE is defined as an AE that starts any time from initiation of JCARH125 administration through and including 90 days following the JCARH125 infusion graded by Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Any AE occurring after the initiation of another anticancer treatment is not considered a TEAE. Grade 3=Severe; Grade 4=Life-threatening.
Number of Participants Receiving Prophylactic Anakinra With Grade ≥2 Cytokine Release Syndrome (CRS) in Phase 1 and Phase 1 Anakinra
Time frame: From first infusion to up to aproximately 61 months
Number of participants receiving prophylactic anakinra with grade ≥ 2 CRS relative to the number of participants treated at the recommended Phase 2 dose (RP2D) in the Phase 1 dose escalation portion of the trial with grade ≥ 2 CRS. CRS grade is defined by the most severe symptom (excluding fever). Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening
Time to Onset of Grade ≥2 Cytokine Release Syndrome (CRS) in Phase 1 and Phase 1 Anakinra
Time frame: From JCARH125 infusion to the first onset of Grade ≥2 CRS (Up to approximately 61 months)
Time to first onset of Grade ≥2 CRS in participants receiving prophylactic anakinra relative to onset of Grade ≥ 2 CRS in participants treated at the RP2D(s) in the Phase 1 dose escalation portion of the trial. Time to onset is calculated from the latest JCARH125 infusion prior to the first onset of Grade >= 2 CRS. CRS grade is defined by the most severe symptom (excluding fever). Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening
Number of Participants Receiving Prophylactic Anakinra With no Cytokine Release Syndrome (CRS) Occurring on Days 1-3 in Phase 1 Anakinra
Time frame: Day 1, 2, 3
The number of participants receiving prophylactic anakinra with no CRS occurring on study days 1, 2, or 3. CRS grade is defined by the most severe symptom (excluding fever). Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening
Overall Response Rate (ORR) in Phase 2 and Phase 2a
Time frame: From the time of the JCARH125 infusion until disease progression, end of study, or the start of another anticancer therapy or stem cell transplant (Up to aproximately 61 months)
ORR is defined as stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR), according to IMWG criteria. Participants without any reported disease response assessments will be considered non-responders. sCR=complete response plus normal free light chain ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR=negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates. When the only method to measure disease is by serum FLC levels, CR can be defined as a normal FLC ratio of 0.26 to 1.65; VGPR=serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein level plus urine M-protein level < 100 mg/24 h; PR=≥ 50% reduction of serum M protein plus reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg/24 h
19 secondary outcomes
Maximum Observed Concentration (Cmax)
Time frame: From JCARH125 infusion through the day 29 visit
Time to Maximum Observed Concentration (Tmax)
Time frame: From JCARH125 infusion through the day 29 visit
Area Under the Concertation-Time Curve (AUC) From Time Day 1 to Day 29 [AUC (0-28 Days)]
Time frame: From JCARH125 infusion through 28 days after the infusion
Number of Participants With Pharmacokinetics Persistence
Time frame: Day 29, 60, 90, 180, 270, 365, 545, 730
Overall Response Rate (ORR) in Phase 1 and Phase 1 Anakinra
Time frame: From the time of the JCARH125 infusion until disease progression, end of study, or the start of another anticancer therapy or stem cell transplant (Up to 61 approximately months)
Complete Response Rate (CRR)
Time frame: From the time of the JCARH125 infusion until disease progression, end of study, or the start of another anticancer therapy or stem cell transplant (Up to aproximately 61 months)
Duration of Response (DoR) in Phase 2 and 2a
Time frame: From first response to the date of progression or death due to any cause, whichever occurs first (Up to approixmately 61 months)
Duration of Complete Response (DoCR) in Phase 2 and 2a
Time frame: From first response to the date of progression or death due to any cause, whichever occurs first (Up to approixmately 61 months)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity in Phase 2 and Phase 2a
Time frame: From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)
Number of Participants With Clinically Significant Laboratory Abnormalities by Severity in Phase 2 and Phase 2a
Time frame: From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)
Overall Survival (OS) in Phase 2 and Phase 2a
Time frame: Form date of first infusion to the date of death due to any reason (Up to apprixamtely 61 months)
Progression Free Survival (PFS) in Phase 2 and Phase 2a
Time frame: Form date of first infusion to the date of disease progression, or death, due to any reason (Up to approximately 61 months)
Time to Response (TTR) in Phase 2 and Phase 2a
Time frame: Form date of first infusion to the date of disease progression, or death, due to any reason (Up to approximately 61 months)
Time to Complete Response (TTCR) in Phase 2 and Phase 2a
Time frame: Form date of first infusion to the date of disease progression, or death, due to any reason (Up to approximately 61 months)
Change From Baseline in the Total Score of European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) in Phase 2
Time frame: Baseline and visit 24 month
Change From Baseline in the Total Score of European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ-MY20) in Phase 2
Time frame: Baseline and visit 24 month
Change From Baseline (EQ-5D-5L) Index Score in Phase 2
Time frame: Baseline and visit 24 month
Duration of Hospitalization From JCARH125 Administration in Phase 2
Time frame: From JCARH125 infusion to up to approximately 61 months
Reasons for Hospitalization From JCARH125 Administration in Phase 2
Time frame: From JCARH125 infusion to up to approximately 61 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BMS Clinical Trial InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
20 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 JCARH125 and JCARH125 + anakinra in people with Multiple Myeloma, run by Juno Therapeutics, a Subsidiary of Celgene at 20 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 13 inclusion and 12 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 24 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 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 May 2024). 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?
Number of Participants With Dose-Limiting Toxicity (DLT) in Phase 1 (time frame: From day 1 to day 22 following JCARH125 infusion (Up to 21 days)). The study lists 7 primary outcomes in all. 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 24 May 2024.