NCT03430011 · REGISTRY CONDITION SEARCH

Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2024-05-24

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Dose-Limiting Toxicity (DLT) in Phase 1

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outcome · POSTED

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity in Phase 1 and Phase 1 Anakinra

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outcome · POSTED

Number of Participants With Clinically Significant Laboratory Abnormalities by Severity in Phase 1 and Phase 1 Anakinra

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outcome · POSTED

Number of Participants Receiving Prophylactic Anakinra With Grade ≥2 Cytokine Release Syndrome (CRS) in Phase 1 and Phase 1 Anakinra

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outcome · POSTED

Time to Onset of Grade ≥2 Cytokine Release Syndrome (CRS) in Phase 1 and Phase 1 Anakinra

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outcome · POSTED

Number of Participants Receiving Prophylactic Anakinra With no Cytokine Release Syndrome (CRS) Occurring on Days 1-3 in Phase 1 Anakinra

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outcome · POSTED

Overall Response Rate (ORR) in Phase 2 and Phase 2a

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outcome · POSTED

Maximum Observed Concentration (Cmax)

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outcome · POSTED

Time to Maximum Observed Concentration (Tmax)

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outcome · POSTED

Area Under the Concertation-Time Curve (AUC) From Time Day 1 to Day 29 [AUC (0-28 Days)]

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outcome · POSTED

Number of Participants With Pharmacokinetics Persistence

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outcome · POSTED

Overall Response Rate (ORR) in Phase 1 and Phase 1 Anakinra

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outcome · POSTED

Complete Response Rate (CRR)

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outcome · POSTED

Duration of Response (DoR) in Phase 2 and 2a

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outcome · POSTED

Duration of Complete Response (DoCR) in Phase 2 and 2a

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outcome · POSTED

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity in Phase 2 and Phase 2a

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outcome · POSTED

Number of Participants With Clinically Significant Laboratory Abnormalities by Severity in Phase 2 and Phase 2a

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outcome · POSTED

Overall Survival (OS) in Phase 2 and Phase 2a

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outcome · POSTED

Progression Free Survival (PFS) in Phase 2 and Phase 2a

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outcome · POSTED

Time to Response (TTR) in Phase 2 and Phase 2a

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outcome · POSTED

Time to Complete Response (TTCR) in Phase 2 and Phase 2a

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Change From Baseline (EQ-5D-5L) Index Score in Phase 2

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outcome · POSTED

Duration of Hospitalization From JCARH125 Administration in Phase 2

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outcome · POSTED

Reasons for Hospitalization From JCARH125 Administration in Phase 2

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Key Inclusion Criteria: 1. 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): 1. Autologous stem cell transplant 2. A regimen that included an immunomodulatory agent (eg, thalidomide, lenalidomide, pomalidomide) and a proteasome inhibitor (eg, bortezomib, carfilzomib, ixazomib), either alone or in combination 3. 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. 2. Subjects must have measurable disease. 3. Subject must be willing to provide fresh bone marrow biopsy samples during Screening (and prior to study treatment, if required). 4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 5. Adequate renal, bone marrow, hepatic, pulmonary, and cardiac function 6. 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: 1. 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. 2. Subjects who have received prior BCMA-directed T-cell engager therapy. 3. Subjects who have received prior BCMA-directed antibody-drug conjugate therapy. Exclusion Criteria: 1. Subjects with known active or history of CNS involvement by malignancy 2. 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 3. Subjects who are considered eligible to receive and have not refused an autologous stem cell transplant 4. 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. 5. Require systemic immunosuppressive therapies (eg, calcineurin inhibitors, methotrexate, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-IL-6 or anti-IL-6 receptor \[IL-6R\]) 6. Prior CAR T-cell or other genetically-modified T-cell therapy (not applicable for subjects enrolled in Phase 2a cohorts) 7. Prior treatment with a BCMA-targeted agent (not applicable for subjects enrolled in Phase 2a cohorts) 8. 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 9. 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. 10. 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 11. Subjects with known hypersensitivity to E Coli-derived proteins (only applicable to subjects in Phase 1 Anakinra Cohort) 12. History of severe immediate hypersensitivity reaction to any of the protocol-mandated or recommended agents used in this study
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Subjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by a single dose of JCARH125
intervention Names
Biological: JCARH125
label
JCARH125
type
EXPERIMENTAL
description
Subjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by prophylactic treatment with anakinra and a single dose of JCARH125
intervention Names
Biological: JCARH125 + anakinra
label
JCARH125 + anakinra
type
EXPERIMENTAL

interventions

arm Group Labels
JCARH125
description
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).
name
JCARH125
type
BIOLOGICAL
arm Group Labels
JCARH125 + anakinra
description
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.
name
JCARH125 + anakinra
type
BIOLOGICAL

Study design

allocation

NON_RANDOMIZED

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 165
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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
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)
description
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.
measure
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)
description
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.
measure
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)
description
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
measure
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
description
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
measure
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)
description
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
measure
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
description
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
measure
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)

secondary Outcomes

description
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.
measure
Maximum Observed Concentration (Cmax)
time Frame
From JCARH125 infusion through the day 29 visit
description
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.
measure
Time to Maximum Observed Concentration (Tmax)
time Frame
From JCARH125 infusion through the day 29 visit
description
AUC (0-28) of JCARH125 CAR T cells in the blood as determined by quantitative polymerase chain reaction (qPCR) to detect the JCARH125 transgene.
measure
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
description
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).
measure
Number of Participants With Pharmacokinetics Persistence
time Frame
Day 29, 60, 90, 180, 270, 365, 545, 730
description
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
measure
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)
description
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
measure
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)
description
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.
measure
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)
description
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.
measure
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)
description
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.
measure
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)
description
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.
measure
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)
description
OS is defined as the time from the JCARH125 infusion until death due to any cause.
measure
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)
description
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.
measure
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)

Full study description

brief 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. 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.

Source references