Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunomodulating Agents

Interleukin 1 Receptor Antagonist Protein

Subjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by a single dose of JCARH125

Subjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by prophylactic treatment with anakinra and a single dose of JCARH125

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

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.

JCARH125 + anakinra

Bristol-Myers Squibb

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

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

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

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.

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 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 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

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

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

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.

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.

AUC (0-28) of JCARH125 CAR T cells in the blood as determined by quantitative polymerase chain reaction (qPCR) to detect the JCARH125 transgene.

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).

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

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.

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.

OS is defined as the time from the JCARH125 infusion until death due to any cause.

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.

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.

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.

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.

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.

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

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.

Number of participants with reasons for hospitalization from JCARH125 administration

Juno Therapeutics, a Subsidiary of Celgene

The total number at risk for all-cause mortality represents all participants who underwent leukapheresis. The total number at risk by any serious adverse event and other (not including serious) adverse events represents all participants that received at least 1 infusion of study medication (JCARH125).

JCARH125 IV at dose level 50 x 10\^6 consisting of CD3+CAR+T cells

Phase 1 50 x 10^6 Cells

JCARH125 IV at dose level 150 x 10\^6 consisting of CD3+CAR+T cells

Phase 1 150 x 10^6 Cells

JCARH125 IV at dose level 300 x 10\^6 consisting of CD3+CAR+T cells

Phase 1 300 x 10^6 Cells

JCARH125 IV at dose level 450 x 10\^6 consisting of CD3+CAR+T cells

Phase 1 450 x 10^6 Cells

JCARH125 IV at dose level 600 x 10\^6 consisting of CD3+CAR+T cells

Phase 1 600 x 10^6 Cells

2 doses of 100 mg anakinra administered subcutaneously (SC) for 5 consecutive days + JCARH125 IV at dose level 600 x 10\^6 consisting of CD3+CAR+T cells

Phase 1 Anakinra 600 x 10^6 Cells

JCARH125 IV at dose level 600 x 10\^6 consisting of CD3+CAR+T cells expansion

Phase 2 600 x 10^6 Cells

JCARH125 IV at dose level 600 x 10\^6 consisting of CD3+CAR+T cells in participants previously treated with BCMA-directed anti-myeloma therapy

Phase 2a 600 x 10^6 Cells Anti-BCMA

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Bristol-Myers Squibb Study Director

All participants who have either experienced a DLT or were followed for the full DLT evaluation period in phase 1

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

TEAE

Grade 3-5 TEAE

Grade 5 TEAE

JCARH125-Related TEAE

JCARH125-Related Grade 3-5 TEAE

JCARH125-Related Grade 5 TEAE

All participants who received at least one infusion of JCARH125 (and at least one dose of anakinra as prophylactic intervention for phase 1 Anakinra) in phase 1 and in phase 1 Anakinra

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

Neutropenia grade 3

Neutropenia grade 4

Anemia grade 3

Thrombocytopenia grade 3

Thrombocytopenia grade 4

Leukopenia grade 3

Leukopenia grade 4

Lymphopenia grade 3

Lymphopenia grade 4

Febrile neutropenia grade 3

Febrile neutropenia grade 4

Haemolysis grade 3

Hypofibrinogenaemia grade 3

Hypophosphataemia grade 3

Hypophosphataemia grade 4

Hypocalcaemia grade 3

Hypocalcaemia grade 4

Hypokalaemia grade 3

Hyponatraemia grade 3

Hypomagnesaemia grade 3

Hyperglycaemia grade 3

Hyperglycaemia grade 4

Hypoalbuminaemia grade 3

Hypertriglyceridaemia grade 3

Hypertriglyceridaemia grade 4

Alanine aminotransferase increased grade 3

Aspartate aminotransferase increased grade 3

Aspartate aminotransferase increased grade 4

Blood alkaline phosphatase increased grade 3

Blood bilirubin increased grade 3

Serum ferritin increased grade 3

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

All participants who received at least one infusion of JCARH125 (and at least one dose of anakinra as prophylactic intervention for phase 1 Anakinra), at dose level 600 x 10\^6 in phase 1 and in phase 1 Anakinra

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

All participants with grade ≥2 CRS who received at least one infusion of JCARH125 (and at least one dose of anakinra as prophylactic intervention for phase 1 Anakinra) at dose level 600 x 10\^6 in phase 1 and in phase 1 Anakinra

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

All participants who received at least one infusion of JCARH125 and at least one dose of anakinra as prophylactic intervention in phase 1 Anakinra

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

All participants who received conforming JCARH125 cell product at the recommended phase 2 dose and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion in phase 2 and in phase 2a

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

All participants who have the necessary PK measurements to provide interpretable results for this specific parameter of interest

Maximum Observed Concentration (Cmax)

Time to Maximum Observed Concentration (Tmax)

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

Day 29

Day 60

Day 90

Day 180

Day 270

Day 365

Day 545

Day 730

All participants who have the necessary PK measurements to provide interpretable results for the specific parameters of interest

Number of Participants With Pharmacokinetics Persistence

All participants who received conforming JCARH125 cell product at the recommended phase 2 dose (and at least one dose of anakinra as prophylactic intervention for phase 1 Anakinra) and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion in phase 1 and in phase 1 Anakinra

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

All participants who received conforming JCARH125 cell product at the recommended phase 2 dose (and at least one dose of anakinra as prophylactic intervention for phase 1 Anakinra) and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion

Complete Response Rate (CRR)

All participants with sCR, CR, VGPR, or PR who received conforming JCARH125 cell product at the recommended phase 2 dose and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion in phase 2 and in phase 2a

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

All participants with sCR or CR who received conforming JCARH125 cell product at the recommended phase 2 dose and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion in phase 2 and in phase 2a

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

All participants who received at least one infusion of JCARH125 in phase 2 and in phase 2a

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

Lactic acidosis grade 3

Alanine aminotransferase increased grade 4

Blood fibrinogen decreased grade 3

Blood fibrinogen decreased grade 4

CD4 lymphocytes decreased grade 3

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

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

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

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

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

Global Health Status/QoL Month 24

Physical Functioning Month 24

Role Functioning Month 24

Emotional Functioning Month 24

Cognitive Functioning Month 24

Social Functioning Month 24

Fatigue Month 24

Pain Month 24

Nausea and Vomiting Month 24

Dyspnea Month 24

Insomnia Month 24

Appetite Loss Month 24

Constipation Month 24

Diarrhea Month 24

Financial Difficulties Month 24

All participants who received at least one infusion of JCARH125 with baseline and post-baseline assessment at the respective visit in phase 2 only as prespecified in the protocol

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

Disease Symptoms

Side Effects of Treatment

Future Perspectives

Body Image

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma	NCT03430011	Multiple Myelom...	JCARH125 JCARH125 + anak...	18 Years -	Juno Therapeutics, a Subsidiary of Celgene
Long-term Follow-up Study for Patients Previously Treated With a Juno CAR T-Cell Product	NCT03436771	Non Hodgkin Lym... Multiple Myelom... Chronic Lymphoc... Diffuse Large B... Mantle Cell Lym... Follicular Lymp...	JCAR017 JCARH125	-	Juno Therapeutics, a Subsidiary of Celgene
Long-term Follow-up Study for Patients Previously Treated With a Juno CAR T-Cell Product	NCT03436771	Non Hodgkin Lym... Multiple Myelom... Chronic Lymphoc... Diffuse Large B... Mantle Cell Lym... Follicular Lymp...	JCAR017 JCARH125	-	Juno Therapeutics, a Subsidiary of Celgene

Spots Global Cancer Trial Database for jcarh125

Every month we try and update this database with for jcarh125 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for jcarh125

Every month we try and update this database with for jcarh125 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for jcarh125 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.