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Recurrent Multiple MyelomaPhase 1NCT05950113

CART-BCMA/CS1 in Treating Patients With Relapsed or Refractory Multiple Myeloma

A Phase 1 study testing Bone Marrow Aspiration, Bone Marrow Biopsy and Computed Tomography in people with Recurrent Multiple Myeloma and Refractory Multiple Myeloma, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I trial studies the side effects and how well CART-BCMA/CS1 works in treating patients with multiple myeloma (MM) that has come back (relapsed) or that does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 to 74 years
What is being tested?
Bone Marrow Aspiration, Bone Marrow Biopsy and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
28 Mar 2024to 28 Mar 2028
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 74 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of multiple myeloma relapsed or refractory after at least three prior lines of therapy, including:
  • A proteasome inhibitor and immunomodulatory agent either alone or in combination
  • Anti-CD38 (Cluster of Differentiation 38) directed therapy
  • Patients previously treated with anti-BCMA directed therapy are allowed onto the study. Patients must not have a history of grade > 3 CRS or grade >= 3 immune effector cell associated neurotoxicity (ICANS) with prior anti-BCMA therapy
  • Patients must have measurable MM as defined by at least one of the criteria below:
  • Serum M-protein >= 0.5 g/dl (5 g/L)
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  • Urine M-protein >= 200 mg/24 h
  • Serum free light chain (FLC) assay: involved FLC level >= 10 mg/dl (100 mg/l) provided serum FLC ratio is abnormal
  • A biopsy-proven plasmacytoma
  • Age >= 18 years old and =< 74 years old
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Absolute neutrophil count (ANC) >= 1 x 10^9 cells/L. Granulocyte colony stimulating factor is permitted (within 30 days prior to enrollment using standard phase I criteria for organ function)
  • Platelets >= 50 x 10^9/L. Without transfusion, growth factors may be used to achieve eligibility criteria (within 30 days prior to enrollment using standard phase I criteria for organ function)
  • Hemoglobin >= 8 g/dL (with or without transfusion) (within 30 days prior to enrollment using standard phase I criteria for organ function)
  • Aspartate and alanine aminotransferases (AST, ALT) =< 2.5 x upper limit of normal (ULN) (within 30 days prior to enrollment using standard phase I criteria for organ function)
  • Total bilirubin =< 2 x ULN (except patients with documented Gilbert's syndrome) (Within 30 days prior to enrollment using standard phase I criteria for organ function)
  • Creatinine clearance >= 30 mL/min (within 30 days prior to enrollment using standard phase I criteria for organ function)
  • Must be willing and able to accept at least one leukapheresis procedure
  • Must be willing and able to provide written informed consent

Who cannot join

  • Inability to purify >= 5 x 10^8 CD62L-enriched cells from leukapheresis product
  • Previously known hypersensitivity to any of the agents used in this study; known sensitivity to cyclophosphamide or fludarabine
  • Received systemic treatment for multiple myeloma, including immunotherapy, within 14 days prior to initiation of lymphodepletion chemotherapy administration within this protocol. Consistent with current trials, patients may otherwise be given bridging therapy at the discretion of the lead study investigator
  • Prior allogeneic hematopoietic stem cell transplantation
  • Autologous hematopoietic stem cell transplantation within 12 weeks prior to enrollment. Patients who have received an autologous transplant over 12 weeks from enrollment will not be excluded and may participate in the trial
  • Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or having received systemic steroids within the last 2 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed)
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  • Human immunodeficiency virus (HIV) seropositivity or other congenital or acquired immune deficiency state, which would increase the risk of opportunistic infections and other complications during chemotherapy-induced lymphodepletion. If there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
  • Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the lymphodepletion chemotherapy regimen and supportive treatments. Patients with hepatitis C seropositive disease but undetectable hepatic C virus (HCV) ribonucleic acid (RNA) viral load will be allowed in the trial. Patients with B seropositivity on antiviral therapy will be allowed in the trial
  • Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
  • Known clinically active central nervous system involvement (CNS). Prior evidence of CNS involvement successfully treated will not be an exclusion for participation as long as they are deemed under control at the time of study enrollment and there are no neurological signs of potential CNS involvement. A brain magnetic resonance imaging (MRI) scan taken within 8 weeks of lymphodepletion may be used, otherwise a brain MRI must be performed to confirm absence of CNS involvement
  • Oxygen saturation of =< 92% on room air
  • A left ventricular ejection fraction =< 45%
  • Pregnancy or breast-feeding. Female patients must be surgically sterile or be postmenopausal for two years or must agree to use effective contraception during the period of treatment and for 6 months afterwards. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) at screening and again within 14 days from starting the lymphodepletion chemotherapy. The definition of effective contraception will be based on the judgment of the study investigators. Patients who are breastfeeding are not allowed on this study
  • History of other malignancy in the past 3 years with the following exceptions:
  • Malignancy treated with curative intent and no known active disease
  • Adequately treated non-melanoma skin cancer without evidence of disease
  • Adequately treated cervical carcinoma in situ without evidence of disease
  • Adequately treated breast ductile carcinoma without evidence of disease
  • Prostate cancer with a Gleason score less than 6 with undetectable prostate specific antigen over 12 months
  • Adequately treated urothelial non-invasive carcinoma or carcinoma in situ
  • Similar neoplastic conditions with an expectation of greater than 95% disease free survival

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Melanie Ayala Ceja

    Los Angeles, California, 90095

Other trials in United States

About this study

Official title: Phase I Dose-Escalation Study of BCMA/CS1 Bispecific Chimeric Antigen Receptor (CAR)-T Cells for Relapsed/Refractory Multiple Myeloma

This phase I trial studies the side effects and how well CART-BCMA/CS1 works in treating patients with multiple myeloma (MM) that has come back (relapsed) or that does not respond to treatment (refractory). Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers, including MM. Immune cells can be engineered to kill MM cells by inserting a piece of deoxyribonucleic acid (DNA) into the immune cells using a lentiviral vector, that allows them to recognize MM cells.

CART-BCMA cells are such modified T cells that target markers called CS1 or B-cell maturation antigen (BCMA), which is expressed by a type of white blood cell called a "B-cell", which are cells that may help the MM cells grow. These engineered CART-BCMA/CS1 cells may kill MM cells.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the safety of CART-BCMA/CS1 cells in patients with R/R MM for determination of a recommended phase 2 dose (RP2D).

SECONDARY OBJECTIVES:

  1. To describe the overall adverse event profile of CART-BCMA/CS1 cells. II. To investigate the efficacy of CART-BCMA/CS1 cells. III. To evaluate the persistence of CART-BCMA/CS1 cells.

EXPLORATORY OBJECTIVES:

  1. To characterize the cytokine environment following CART-BCMA/CS1 cell infusion and to evaluate changes in the setting of CRS.

II. To evaluate changes in T-cell subsets and function following CART-BCMA/CS1 cell infusion.

III. To examine the change in expression of BCMA and CS1 on clonal plasma cells in the bone marrow and/or extramedullary disease after CART-BCMA/CS1 cell treatment.

IV. To evaluate for plasma-cell aplasia.

OUTLINE: This is a first-in-human, phase I, single-arm, open-label, dose-escalation study.

Patients undergo leukapheresis 35 to 21 days before Infusion Day (I-Day -35 to I-Day -21) and receive cyclophosphamide intravenously (IV) over 60 minutes and fludarabine IV over 30 minutes on I-Days -5, -4, and -3. Patients then receive the CART-BCMA/CS1 infusion IV on I-Day -0 on study. Patients undergo echocardiography (ECHO), electrocardiogram (ECG), and magnetic resonance imaging (MRI) during screening. Patients undergo bone marrow biopsy and/or bone marrow aspirate screening, between I-Day -28 to I-Day -5, I-Day 30, and at 1 year post CART-BCMA/CS1 infusion. Patients also undergo fluorodeoxyglucose F-18 (FDG) positron emission tomography/computed tomography (PET/CT) during screening, between I-Day -28 to I-Day -5, I-Day 90 and I-Day 180 and every 3 months thereafter.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months until 5 years, then annually for 15 years.

Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow biopsy and aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy and aspiration

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo PET/CT

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Receive IV

  • EchocardiographyProcedure or surgery

    Also called EC

    Undergo ECHO

  • FludarabineDrug

    Also called Fluradosa

    Receive IV

  • Fludeoxyglucose F-18Other

    Also called 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18

    Receive IV

  • ImmunotherapyOther

    Also called Immunological, Immunological Therapy, Immunologically Directed Therapy

    Receive CART-BCMA/CS1 cells IV

  • LeukapheresisProcedure or surgery

    Also called Leukocytopheresis, Therapeutic Leukopheresis

    Undergo leukapheresis

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

Study groups in NCT05950113
Study groupRoleWhat they receive
Treatment (CART-BCMA/CS1)ExperimentalPatients undergo leukapheresis on 35 to 21 days before Infusion Day (I-Day -35 to I-Day -21) and receive cyclophosphamide IV over 60 minutes and fludarabine IV over 30 minutes on I-Days -5, -4, and -3. Patients then receive CART-BCMA/CS1 IV on I-Day-0 on study. Patients undergo ECHO, ECG and MRI during screening. Patients undergo bone marrow biopsy and/or bone marrow aspirate screening, between I-Day -28 to I-Day -5, I-Day 30, and at 1 year post CART-BCMA/CS1 infusion. Patients also undergo FDG PET/CT during screening, between I-Day -28 to I-Day -5, I-Day 90 and I-Day 180 and every 3 months thereafter.
Receives: Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Echocardiography; Drug: Fludarabine; Other: Fludeoxyglucose F-18; Other: Immunotherapy; Procedure: Leukapheresis; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose limiting toxicities (DLTs)

    Will be assessed by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v. 5). For cytokine release syndrome (CRS) and neurotoxicity, patients will be evaluated using the grading criteria outlined by the American Society for Transplantation and Cellular Therapy (ASTCT).

    Measured: Within 28 days from CART-BCMA/CS1 cell infusion

Secondary outcomes (7)

  1. Incidence of adverse events

    Will be assessed by CTCAE v. 5 and occurrence and grade of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT criteria.

    Measured: Up to 15 years

  2. Clinical response rate

    Will be assessed according to to the International Myeloma Working Group (IMWG) Uniform Response criteria, including minimum residual disease (MRD). MRD status for patients in complete remission (CR) will be summarized. Rates of best response of >= complete response (CR) or >= very good partial response (VGPR) may be summarized.

    Measured: Up to 2 years

  3. Overall response rate

    Will be summarized with the frequency count and percentage of patients in each category

    Measured: Up to 2 years

  4. Duration of response

    Will be measured after treatment from the time measurement criteria is met for stringent complete response (sCR), CR, VGPR, or partial response (PR) until the first date that progressive disease (PD) is objectively documented or until death. Will be summarized using the Kaplan-Meier method.

    Measured: Up to 2 years

  5. Overall survival

    Will be summarized using the Kaplan-Meier method. The Kaplan-Meier estimates for the 1-year Overall Survival (OS) rates and the 2-sided 95% confidence interval of the rates using the Greenwood's formula will be reported and will be summarized descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum) and will be summarized descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum).

    Measured: The date of CART-BCMA/CS1 cell infusion in the study until death, assessed up to 15 years

  6. Progression free survival

    Will be summarized using the Kaplan-Meier method.

    Measured: The date of CART-BCMA/CS1 cell infusion until documentation of PD, or death due to any cause, assessed up to 2 years

  7. CART-BCMA/CS1 cell persistence

    Expansion and persistence of CART-BCMA/CS1 cells will be monitored with Real-time polymerase chain reaction (qPCR) specific to CART-BCMA/CS1 lentiviral elements in order to quantify the vector copy number. DNA will be extracted from peripheral blood cells and assessed with primers specific to genetic elements inserted by the lentivirus. Analysis will be performed to determine the number of days until CART-BCMA/CS1 cells are no longer detectable by polymerase chain reaction (PCR).

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jul 2023
  2. Study start28 Mar 2024 (estimated)
  3. Primary completion28 Mar 2027 (estimated)
  4. Study completion28 Mar 2028 (estimated)

Why it stopped: The study was withdrawn before opening

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05950113
Sponsor's protocol ID
23-000577
Other IDs
NCI-2023-04271
Status last verified
Apr 2024
First submitted
10 Jul 2023
Last updated
1 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bone Marrow Aspiration, Bone Marrow Biopsy and Computed Tomography in people with Recurrent Multiple Myeloma and Refractory Multiple Myeloma, run by Jonsson Comprehensive Cancer Center at 1 site 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 19 inclusion and 21 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: withdrawn, as of the sponsor's last update on 1 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 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Incidence of dose limiting toxicities (DLTs) (time frame: Within 28 days from CART-BCMA/CS1 cell infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05950113.

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 1 May 2024.

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