CompletedNCT02215967Updated Oct 8, 2019Results posted

Study of T Cells Targeting B-Cell Maturation Antigen for Previously Treated Multiple Myeloma

A Phase 1 interventional study of Cyclophosphamide and Fludarabine in Myeloma, Plasma-Cell and Myeloma-Multiple, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years to 73 Years. Per ClinicalTrials.gov, last updated 2019-10-08.

Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 30
Ages: 18 Years to 73 Years
Sex: All

Study summary

Background:

T cells are white blood cells that fight several cancers. One cancer therapy involves removing a persons' T cells, changing them in a lab, and then returning them to the person. Researchers want to see if this helps people with multiple myeloma.

Objective:

To test the safety of giving anti-B-Cell Maturation Antigen T cells to people with multiple myeloma.

Eligibility:

Adults ages 18-70 with multiple myeloma that has not responded to standard therapies.

Design:

Participants may be screened with:
Medical history
Physical exam
Blood and urine tests
Heart tests
Bone marrow sample
Multiple scans and X-rays
Participants will have apheresis. Blood is removed through a needle in an arm. T cells are removed. The rest of the blood is returned through a needle in the other arm.
The cells will be changed in a laboratory.
Participants will get 2 chemotherapy drugs over 3 days.
Two days later, participants will check into the hospital. They will get an intravenous (IV) catheter in an arm or chest vein. They will get the T cells through the IV in 1 infusion.
After this, participants will stay in the hospital for at least 9 days and stay nearby for 2 weeks. Then they will have blood tests and see a doctor.
Participants will visit the clinic 1, 2, 3, 4, 6, and 12 months after the infusion, then every 6 months. A bone marrow sample will be taken at the 2-month visit.
Participants blood will be collected for several years. Participants will have an annual physical at National Institutes of Health (NIH) for 5 years after the infusion. Then for 10 years they will answer health questionnaires.

Read the detailed description

BACKGROUND:

Multiple myeloma (MM) is a malignancy of plasma cells.
MM is nearly always incurable.
T cells can be genetically modified to express chimeric antigen receptors (CARs) that specifically target malignancy-associated antigens.
Autologous T cells genetically modified to express CARs targeting the B-cell antigen cluster of differentiation 19 (CD19) have caused complete remissions in a small number of patients with leukemia or lymphoma. These results demonstrate that CAR-expressing T cells have anti-malignancy activity in humans.
B-cell maturation antigen (BCMA) is a protein expressed by normal plasma cells and the malignant plasma cells of multiple myeloma.
BCMA is not expressed by normal cells except for plasma cells and some mature B cells.
We have constructed an anti-BCMA CAR that can specifically recognize BCMA-expressing target cells in vitro and eradicate BCMA-expressing tumors in mice.
Anti-BCMA-CAR-expressing T cells have not been previously tested in humans.
We hypothesize that anti-BCMA-CAR-expressing T cells will specifically eliminate

BCMA-expressing MM cells in patients

-Possible toxicities include cytokine-associated toxicities such as fever, hypotension, and neurological toxicities. Elimination of normal plasma cells and unknown toxicities are also possible.

OBJECTIVES:

Primary

-Determine the safety and feasibility of administering T cells expressing an anti- BCMA CAR to patients with MM.

Secondary

Evaluate the in vivo persistence of anti-BCMA CAR T cells
Assess for evidence of anti-myeloma activity by anti-BCMA CAR T cells

ELIGIBILITY

Patients must have measurable MM defined as a serum M-protein greater than or equal to 0.4 g/dL or a urine M-protein greater than or equal to 200 mg/24 hours or an involved serum free light chain (FLC) level greater than or equal to 10 mg/dL (provided FLC ratio is abnormal) or a biopsy-proven plasmacytoma.
Patients must have previously received at least 3 different treatment regimens for MM.
Patients must have a normal creatinine and a normal cardiac ejection fraction.
An Eastern Cooperative Oncology Group (ECOG) performance status of 0 -2 is required.
Patients on any anticoagulant medications except aspirin are not eligible.
No active infections are allowed.
Absolute neutrophil count greater than or equal to 1000/ L, platelet count greater than or equal to 45,000/ L, hemoglobin greater than or equal to 8g/dL
Alanine aminotransferase (ALT) and aspartate transaminase (AST) less than or equal to 2.5-fold higher than the upper limit of normal
At least 14 days must elapse between the time of any prior systemic treatment (including corticosteroids) and the required leukapheresis.
At least 14 days must elapse between the time of any prior systemic treatment (including corticosteroids) and initiation of protocol treatment.
Bone marrow plasma cells must be 30% or less of total bone marrow cells 30 days or less prior to the start of protocol treatment.
The patient's MM will need to be assessed for BCMA expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health (NIH). If unstained, paraffinembedded bone marrow or plasmacytoma sections are available from prior biopsies, these can be used to determine BCMA expression by immunohistochemistry; otherwise patients will need to come to the NIH for a bone marrow biopsy or other biopsy of a plasmacytoma to determine BCMA expression. The sample for BCMA expression can come from a biopsy obtained at any time before enrollment.

DESIGN:

This is a phase I dose-escalation trial
Patients will undergo leukapheresis
T-cells obtained by leukapheresis will be genetically modified to express an anti- BCMA CAR
Patients will receive a lymphocyte-depleting chemotherapy conditioning regimen with the intent of enhancing the activity of the infused anti-BCMA-CAR-expressing T cells.
The chemotherapy conditioning regimen is cyclophosphamide 300 mg/m\^2 daily for 3 days and fludarabine 30 mg/m\^2 daily for 3 days. Fludarabine will be given on the same days as the cyclophosphamide.
Two days after the chemotherapy ends, patients will receive an infusion of anti- BCMA-CAR-expressing T cells.
The initial dose level of this dose-escalation trial will be 0.3x10\^6 CAR+ T cells/kg of recipient bodyweight.
The cell dose administered will be escalated until a maximum tolerated dose is determined for patients in which less than 50% of total bone marrow cells are plasma cells.

With Amendment C, all patients with 50% or greater bone marrow plasma cells will receive 3x10(6) anti-BCMA CAR T cells/kg.

Following the T-cell infusion, there is a mandatory 9-day inpatient hospitalization to monitor for toxicity.
Outpatient follow-up is planned for 2 weeks, and 1, 2, 3, 4, 6, 9, and 12 months after the CAR T-cell infusion.
Repeat treatments are possible for patients with residual MM and no greater than grade 2 toxicity with an initial treatment.
Re-enrollment will be allowed for a small number of subjects.

Conditions studied

Myeloma, Plasma-Cell
Myeloma-Multiple

Browse trials for

Keywords

Immunotherapy
Anti-BCMA-CAR
Gene Therapy
Adoptive T Cell Therapy
Plasma Cell Malignancy

In context

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 30 is below the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 73 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

2.1.1.1 Multiple Myeloma criteria

Clear B-cell maturation antigen (BCMA) expression must be detected on greater than 50% of malignant plasma cells from either bone marrow or a plasmacytoma by flow cytometry or immunohistochemistry. These assays must be performed at the National Institutes of Health. It is not required that the specimen used for BCMA determination comes from a sample that was obtained after the patient's most recent treatment. BCMA expression will need to be documented on the majority of malignant plasma cells at some time after the original anti-BCMA chimeric antigen receptor (CAR) T-cell infusion in all patients undergoing a second anti-BCMA CAR T-cell infusion. If paraffin embedded unstained samples of bone marrow involved with multiple myeloma (MM) or a plasmacytoma are available, these can be shipped to the National Institutes of Health (NIH) for BCMA staining, otherwise new biopsies will need to be performed for determination of BCMA expression.
Bone marrow plasma cells must make up 30% or less of total bone marrow cells based on a bone marrow biopsy performed within 30 days of the start of protocol treatment.
Patients must have received at least 3 different prior treatment regimens for multiple myeloma
Patients must have measurable MM as defined by at least one of the criteria below.
a. One or more of these abnormalities defines measurable disease:
- Serum M-protein greater or equal to 1 g/dl (10 g/l).
- Urine M-protein greater or equal to 200 mg/24 h.
- Serum free light chain (FLC) assay: involved FLC level greater or equal to10 mg/dl (100 mg/l) provided serum FLC ratio is abnormal.
- A biopsy-proven plasmacytoma
Patients must have multiple myeloma that meets the criteria for one of the following Disease categories: (1) progressive disease or (2) relapse from Complete Remission (CR) as described in the International Uniform Response Criteria for Multiple Myeloma and as listed below.
1. Progressive Disease (which requires 1 or more of the following)(A):
  Increase of greater than or equal to 25% from the lowest response value (nadir) in any one or more of these parameters:
  1. Serum M-component (the absolute increase must be greater than or equal to 0.5 g/dL) (B) and/or
  2. Urine M-component and/or (the absolute increase must be greater than or equal to 200 mg/24 h)
  3. Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL.
  4. Bone marrow plasma cell percentage; the absolute percentage must be greater than or equal to 10%
Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas (defined as 50% or greater increase in the sum of the products of the cross-diameters of target lesions)
Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder
1. Relapse from complete remission (A)
Defined as one or more of the following; must be attributable to myeloma:
1. Reappearance of serum or urine M-protein by immunofixation or electrophoresis
2. Development of greater than or equal to 5% plasma cells in the bone marrow
3. Appearance of any other sign of progression (i.e., new plasmacytoma, lytic bone lesion, or hypercalcemia)

(A)All relapse and progression categories require two consecutive assessments made at any time before classification as relapse or disease progression and/or the institution of any new therapy.

(B)For progressive disease, serum M-component increases of greater than or equal to 1 gm/dL are sufficient to define progression if starting M-component is greater than or equal to 5 g/dL.

2.1.1.2 Other inclusion criteria:

Greater than or equal to 18 years of age and less than or equal to age 73.
Able to understand and sign the Informed Consent Document.
Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-2
Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen.
Women of child bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune -competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.)
Seronegative for hepatitis B antigen, positive hepatitis B tests can be further evaluated by confirmatory tests, and if confirmatory tests are negative, the patient can be enrolled.
Seronegative for hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then patients must be tested for the presence of antigen by Reverse transcription polymerase chain reaction (RT-PCR) and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative.
Absolute neutrophil count greater than or equal to 1000/mm\^3 without the support of filgrastim or other growth factors.
Platelet count greater than or equal to 45,000/mm\^3 without transfusion support
Hemoglobin greater than 8.0 g/dl.
Less than 5% plasma cells in the peripheral blood leukocytes
Serum alanine transaminase (ALT) and aspartate transaminase (AST) less or equal to 2.5 times the upper limit of the institutional normal.
Serum creatinine less than or equal to 1.3 mg/dL.
Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
At least 14 days must have elapsed since any prior systemic therapy at the time the patient starts the cyclophosphamide and fludarabine conditioning regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
Because this protocol requires collection of autologous blood cells by leukapheresis in order to prepare anti-BCMA-CAR T cells, systemic anti-myeloma therapy including systemic corticosteroid steroid therapy of greater than 5 mg/day of prednisone or equivalent dose of another corticosteroid are not allowed within 2 weeks prior to the required leukapheresis.
Normal cardiac ejection fraction (greater than or equal to 50% by echocardiography) and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 6 weeks of the start of the treatment protocol.
Patients should not take corticosteroids including prednisone, dexamethasone or any other corticosteroid for any purpose at doses higher than 5 mg/day of prednisone or equivalent dose of another corticosteroid 2 weeks before apheresis and within 2 weeks prior to CAR T-cell infusion, and at any time after the CAR T cell infusion.

Exclusion criteria

2.1.2 EXCLUSION CRITTERIA:

Patients on any anticoagulants except aspirin are not eligible.
Patients that require urgent therapy due to tumor mass effects or spinal cord compression.
Patients that have active hemolytic anemia.
Patients with second malignancies in addition to multiple myeloma are not eligible if the second malignancy has required treatment within the past 3 years or is not in complete remission. There are two exceptions to this criterion: successfully treated non-metastatic basal cell or squamous cell skin carcinoma.
Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
Active systemic infections (defined as infections causing fevers or requiring antimicrobial treatment), active coagulation disorders or other major uncontrolled medical illnesses of the cardiovascular, respiratory, endocrine, renal, gastrointestinal, genitourinary or immune system, history of myocardial infarction, active cardiac arrhythmias, active obstructive or restrictive pulmonary disease.
Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
Systemic corticosteroid steroid therapy of greater than 5 mg/day of prednisone or equivalent dose of another corticosteroid are not allowed within 2 weeks prior to either the required leukapheresis or the initiation of the conditioning chemotherapy regimen.
History of severe immediate hypersensitivity reaction to any of the agents used in this study.
History of allogeneic stem cell transplantation
Patients with central nervous system (CNS) metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions and spinal cord compression).
Patients with active autoimmune skin diseases such as psoriasis or other active autoimmune diseases such as rheumatoid arthritis.

Study design

Phase: Phase 1
Primary purpose: Treatment
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 30 participants (actual)

Study arms

Experimental
Multiple Myeloma
Dose Escalation with 5 dose levels based on the patients actual bodyweight
Drug: Cyclophosphamide · Drug: Fludarabine · Biological: Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cells

Interventions

DrugCyclophosphamide
300 mg/m\^2 intravenous (IV) over 30 minutes on days -5, -4, and -3
Also known as: Cytoxan
DrugFludarabine
30 mg/m\^2 intravenous (IV) over 30 minutes immediately following the cyclophosphamide on day -5, -4, and -3
Also known as: Fludara
BiologicalAnti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cells
0.3x10\^6- 15.0x10\^6 CAR+ T cells per kg of recipient bodyweight one time dose on day 0

What researchers measure

Primary outcomes

Number of Participants With Dose Limiting Toxicities
Dose limiting toxicities are defined as follows: Grade 3 toxicities possibly or probably related to either the anti-BCMA CAR T cells or the fludarabine and cyclophosphamide chemotherapy and lasting more than 7 days. Grade 4 toxicities possibly or probably related to the study interventions.
Time frame: After the start of treatment and up to 60 days
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: Date treatment consent signed to date off study, approx. 3 mos and 7 days for DL 0.3 x 10^6 CAR + T cells, 4 mos and 4 days for 1.0 x 10^6 CAR + T cells, 9 mos and 13 days for 3.0 x 10^6 CAR + T cells, and 48 mos and 12 days for 9.0 x 10^6 CAR + T cells.

Secondary outcomes

Number of Participants With Best Response
Best response was assessed by the International Myeloma Working Group response criteria. Partial Remission (PR) is 50% or greater reduction of serum M-protein and 90% or greater reduction in 24-h urinary M-protein. Progressive Disease (PD) is increases of greater or equal to 25% from the lowest post-treatment (nadir) value in serum M-component or urine component or percentage of bone marrow plasma cells. Definite development of new bone lesions or new plasmacytoma. Very Good Partial Remission (VGPR) is serum and urine M-protein detectable by immunofixation but not on electrophoresis. Stringent Complete Remission (sCR) is normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry. Complete Remission is negative immunofixation on the serum and urine. Stable Disease (SD) is not meeting criteria for CR, VGPR, PR or PD.
Time frame: From start of treatment up to 84 weeks

Results

Posted Oct 8, 2019

Participant flow

Participant flow — Overall Study
Milestone	0.3 x 10^6 CAR-BCMA T-cells Infused	1 x 10^6 CAR-BCMA T-cells Infused	3 x 10^6 CAR-BCMA T-cells Infused	9 x 10^6 CAR-BCMA T-cells Infused
Started	3	3	5	19
Completed	3	3	4	16
Not completed	0	0	1	3
Withdrew: Patient became ineligible for treatment	0	0	0	3
Withdrew: Patient did not get car t-cells	0	0	1	0

Outcome measures

PrimaryNumber of Participants With Dose Limiting Toxicities

Dose limiting toxicities are defined as follows: Grade 3 toxicities possibly or probably related to either the anti-BCMA CAR T cells or the fludarabine and cyclophosphamide chemotherapy and lasting more than 7 days. Grade 4 toxicities possibly or probably related to the study interventions.

Time frame:: After the start of treatment and up to 60 days
Reported as:: Count of participants · Participants

Number of Participants With Dose Limiting Toxicities
Participants	0.3 x 10^6 CAR-BCMA T-cells Infused	1 x 10^6 CAR-BCMA T-cells Infused	3 x 10^6 CAR-BCMA T-cells Infused	9 x 10^6 CAR-BCMA T-cells Infused
Hypophosphatemia	0	0	0	4
Confusion	0	0	0	3
Dyspnea (intubated)	0	0	0	4
Ejection fraction decreased	0	0	0	4
Encephalopathy	0	0	0	3
Hypoxia	0	0	0	3
Acute kidney injury (CVVH)	0	0	0	4
Sepsis (Staph Aureus)	0	0	0	4
Muscle weakness lower limbs	0	0	0	3
Muscle weakness upper limbs	0	0	0	3
Platelet count decreased	0	0	0	3
Neutrophil count decreased	0	0	0	4
Acute kidney injury	0	0	0	3
Hypotension	0	0	0	4
CPK increased	0	0	0	4
Musculoskeletal/connective tissue disorders-Rhabd.	0	0	0	3

PrimaryNumber of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Time frame:: Date treatment consent signed to date off study, approx. 3 mos and 7 days for DL 0.3 x 10^6 CAR + T cells, 4 mos and 4 days for 1.0 x 10^6 CAR + T cells, 9 mos and 13 days for 3.0 x 10^6 CAR + T cells, and 48 mos and 12 days for 9.0 x 10^6 CAR + T cells.
Reported as:: Count of participants · Participants

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
Participants	0.3 x 10^6 CAR-BCMA T-cells Infused	1 x 10^6 CAR-BCMA T-cells Infused	3 x 10^6 CAR-BCMA T-cells Infused	9 x 10^6 CAR-BCMA T-cells Infused
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)	3	3	4	16

SecondaryNumber of Participants With Best Response

Best response was assessed by the International Myeloma Working Group response criteria. Partial Remission (PR) is 50% or greater reduction of serum M-protein and 90% or greater reduction in 24-h urinary M-protein. Progressive Disease (PD) is increases of greater or equal to 25% from the lowest post-treatment (nadir) value in serum M-component or urine component or percentage of bone marrow plasma cells. Definite development of new bone lesions or new plasmacytoma. Very Good Partial Remission (VGPR) is serum and urine M-protein detectable by immunofixation but not on electrophoresis. Stringent Complete Remission (sCR) is normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry. Complete Remission is negative immunofixation on the serum and urine. Stable Disease (SD) is not meeting criteria for CR, VGPR, PR or PD.

Time frame:: From start of treatment up to 84 weeks
Reported as:: Count of participants · Participants

Number of Participants With Best Response
Participants	0.3 x 10^6 CAR-BCMA T-cells Infused	1 x 10^6 CAR-BCMA T-cells Infused	3 x 10^6 CAR-BCMA T-cells Infused	9 x 10^6 CAR-BCMA T-cells Infused
Partial Remission	1	0	0	4
Stable Disease	2	3	3	2
Very Good Partial Remission	0	0	1	6
Complete Remission	0	0	0	1
Stringent Complete Remission	0	0	0	2
Progressive Disease	0	0	0	1

Adverse events

Collected over Date treatment consent signed to date off study, approximately 3 months and 7 days for dose level 0.3 x 10^6 CAR + T cells, 4 months and 4 days for 1.0 x 10^6 CAR + T cells, 9 months and 13 days for 3.0 x 10^6 CAR + T cells, and 48 months and 12 days for 9.0 x 10^6 CAR + T cells.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
0.3 x 10^6 CAR-BCMA T-cells Infused	0/3 (0%)	1/3 (33.3%)	3/3 (100%)
1 x 10^6 CAR-BCMA T-cells Infused	0/3 (0%)	0/3 (0%)	3/3 (100%)
3 x 10^6 CAR-BCMA T-cells Infused	0/4 (0%)	1/4 (25%)	4/4 (100%)
9 x 10^6 CAR-BCMA T-cells Infused	0/16 (0%)	11/16 (68.8%)	16/16 (100%)

Most frequent serious events

Showing 10 of 31

Most frequent serious events
Event	0.3 x 10^6 CAR-BCMA T-cells Infused	1 x 10^6 CAR-BCMA T-cells Infused	3 x 10^6 CAR-BCMA T-cells Infused	9 x 10^6 CAR-BCMA T-cells Infused
Neutrophil count decreasedInvestigations	1/3	0/3	1/4	2/16
White blood cell decreasedInvestigations	1/3	0/3	1/4	0/16
DyspneaRespiratory, thoracic and mediastinal disorders	0/3	0/3	1/4	5/16
HypotensionVascular disorders	0/3	0/3	1/4	5/16
FeverGeneral disorders	0/3	0/3	1/4	1/16
Sinus tachycardiaCardiac disorders	0/3	0/3	1/4	3/16
Platelet count decreasedInvestigations	0/3	0/3	0/4	4/16
HypoxiaRespiratory, thoracic and mediastinal disorders	0/3	0/3	0/4	3/16
Acute kidney injuryRenal and urinary disorders	0/3	0/3	0/4	2/16
DeliriumPsychiatric disorders	0/3	0/3	0/4	2/16

Most frequent other events

Showing 10 of 71

Most frequent other events
Event	0.3 x 10^6 CAR-BCMA T-cells Infused	1 x 10^6 CAR-BCMA T-cells Infused	3 x 10^6 CAR-BCMA T-cells Infused	9 x 10^6 CAR-BCMA T-cells Infused
AnemiaBlood and lymphatic system disorders	3/3	2/3	4/4	13/16
Lymphocyte count decreasedInvestigations	3/3	3/3	4/4	14/16
Neutrophil count decreasedInvestigations	3/3	3/3	4/4	16/16
White blood cell decreasedInvestigations	3/3	3/3	4/4	16/16
FeverGastrointestinal disorders	0/3	2/3	0/4	15/16
HypoalbuminemiaMetabolism and nutrition disorders	0/3	0/3	1/4	15/16
HypophosphatemiaMetabolism and nutrition disorders	1/3	1/3	2/4	14/16
NauseaGastrointestinal disorders	2/3	2/3	1/4	12/16
Platelet count decreasedInvestigations	2/3	1/3	2/4	11/16
Sinus tachycardiaCardiac disorders	0/3	0/3	0/4	11/16

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	0.3 x 10^6 CAR-BCMA T-cells Infused	1 x 10^6 CAR-BCMA T-cells Infused	3 x 10^6 CAR-BCMA T-cells Infused	9 x 10^6 CAR-BCMA T-cells Infused	Total
<=18 years	0	0	0	0	0
Between 18 and 65 years	3	3	5	17	28
>=65 years	0	0	0	2	2

Age, Continuous
Age, Continuous(years)	0.3 x 10^6 CAR-BCMA T-cells Infused	1 x 10^6 CAR-BCMA T-cells Infused	3 x 10^6 CAR-BCMA T-cells Infused	9 x 10^6 CAR-BCMA T-cells Infused	Total
Mean	58.93 ± 4.87	54.0 ± .71	55.76 ± 5.65	54.13 ± 6.86	56.49 ± 5.8

Sex: Female, Male
Sex: Female, Male(Participants)	0.3 x 10^6 CAR-BCMA T-cells Infused	1 x 10^6 CAR-BCMA T-cells Infused	3 x 10^6 CAR-BCMA T-cells Infused	9 x 10^6 CAR-BCMA T-cells Infused	Total
Female	3	1	4	7	15
Male	0	2	1	12	15

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	0.3 x 10^6 CAR-BCMA T-cells Infused	1 x 10^6 CAR-BCMA T-cells Infused	3 x 10^6 CAR-BCMA T-cells Infused	9 x 10^6 CAR-BCMA T-cells Infused	Total
Hispanic or Latino	0	0	0	4	4
Not Hispanic or Latino	3	3	5	14	25
Unknown or Not Reported	0	0	0	1	1

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	0.3 x 10^6 CAR-BCMA T-cells Infused	1 x 10^6 CAR-BCMA T-cells Infused	3 x 10^6 CAR-BCMA T-cells Infused	9 x 10^6 CAR-BCMA T-cells Infused	Total
American Indian or Alaska Native	0	0	0	0	0
Asian	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	1	0	2	2	5
White	2	3	3	15	23
More than one race	0	0	0	0	0
Unknown or Not Reported	0	0	0	2	2

Region of Enrollment
Region of Enrollment(participants)	0.3 x 10^6 CAR-BCMA T-cells Infused	1 x 10^6 CAR-BCMA T-cells Infused	3 x 10^6 CAR-BCMA T-cells Infused	9 x 10^6 CAR-BCMA T-cells Infused	Total
United States	3	3	5	19	30

Study locations

1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland 20892, United States

References and documents

Publications

Kochenderfer JN, Rosenberg SA. Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Nat Rev Clin Oncol. 2013 May;10(5):267-76. doi: 10.1038/nrclinonc.2013.46. Epub 2013 Apr 2. PubMed 23546520 ↗
Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, Gress RE, Hakim FT, Kochenderfer JN. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013 Apr 15;19(8):2048-60. doi: 10.1158/1078-0432.CCR-12-2422. Epub 2013 Jan 23. PubMed 23344265 ↗
Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE, Maric I, Stetler-Stevenson M, Phan GQ, Hughes MS, Sherry RM, Yang JC, Kammula US, Devillier L, Carpenter R, Nathan DA, Morgan RA, Laurencot C, Rosenberg SA. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood. 2012 Mar 22;119(12):2709-20. doi: 10.1182/blood-2011-10-384388. Epub 2011 Dec 8. PubMed 22160384 ↗
Brudno JN, Maric I, Hartman SD, Rose JJ, Wang M, Lam N, Stetler-Stevenson M, Salem D, Yuan C, Pavletic S, Kanakry JA, Ali SA, Mikkilineni L, Feldman SA, Stroncek DF, Hansen BG, Lawrence J, Patel R, Hakim F, Gress RE, Kochenderfer JN. T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma. J Clin Oncol. 2018 Aug 1;36(22):2267-2280. doi: 10.1200/JCO.2018.77.8084. Epub 2018 May 29. PubMed 29812997 ↗
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Study documents

Protocol and statistical analysis plan · Sep 21, 2017
Informed consent form · Oct 16, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 8, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02215967
Lead sponsor: National Cancer Institute (NCI)
Responsible party: James Kochenderfer, M.D. (Principal Investigator, National Cancer Institute (NCI)) — Principal investigator
First posted: Aug 13, 2014
Start date: Aug 12, 2014
Primary completion: Apr 25, 2019
Completion: Aug 15, 2019
Results posted: Oct 8, 2019
Last update: Oct 8, 2019

Study contacts

James N Kochenderfer, M.D.

principal investigator · National Cancer Institute (NCI)

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Sep 2019. You cannot join it, but the record below documents what was studied.

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