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Multiple MyelomaPhase 1/2NCT05243212

Study of CAR-BCMA, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Multiple Myeloma

A Phase 1/2 study testing CAR-BCMA in people with Multiple Myeloma and Relapse Multiple Myeloma, run by Sheba Medical Center at 1 site in Israel.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is an open label, abbreviated (3+3) dose escalation study in subjects with RRMM, followed by an extension phase at the selected safe dose. The dose escalation stage will involve recruitment of 3 RRMM patients for 'low' dose (6 x 106 CAR-T cells/kg) CAR-T therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma, Relapse Multiple Myeloma
What is being tested?
CAR-BCMA
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
1 siteIsrael
Study dates
19 Sep 2021to 1 Sep 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

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

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Bone marrow plasma cells must be at least 10% of total bone marrow cells based on a bone marrow biopsy/aspiration performed within 30 days of the start of protocol treatment.
  • Documented diagnosis of multiple myeloma according to IMWG diagnostic criteria.
  • Subjects must have measurable MM as defined by at least one of the criteria below.
  • One or more of these abnormalities defines measurable disease
  • Serum M-protein equal or greater than 0.4 g/dl (10 g/l).
  • Urine M-protein equal or greater than 200 mg/24 h.
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  • 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 received at least 3 prior treatment regimens for multiple myeloma.
  • Greater than or equal to 18 years of age.
  • Able to understand and sign the Informed Consent Document.
  • Clinical performance status of ECOG 0-2
  • Subjects 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 HIV- 1, 2 antibody.
  • Seronegative for hepatitis B surface antigen (HBsAg) or HBsAg positive with negative PCR for HBV nucleotides in blood. (Treatment to prevent HBV reactivation is standard in any case of seropositivity for HBV).
  • Seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then subjects must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
  • Syphilis negative.
  • Absolute neutrophil count greater than or equal to 500/mm3 without the support of filgrastim or other growth factors.
  • Platelet count greater than or equal to 30,000/mm3 without transfusion support
  • Hemoglobin greater than 8.0 g/dl.
  • Less than 5% plasma cells in the peripheral blood leukocytes
  • At least 14 days must have elapsed since any prior systemic therapy at the time the subject starts the cyclophosphamide and fludarabine conditioning regimen, and subjects' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
  • Systemic anti-myeloma therapy including systemic corticosteroid 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, within 2 weeks prior to CAR T-cell infusion, and for 30 days after the CAR T cell infusion, unless required for treatment of toxicity or other medical need.
  • Cardiac ejection fraction greater than or equal to 45% by echocardiography within 6 weeks of the start of the treatment protocol.

Who cannot join

  • Subjects 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 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), or other major uncontrolled medical illnesses.
  • Active HBV and HCV infection which is identified by positive PCR to viral nucleotides in blood.
  • 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.
  • Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 x upper limit of normal (ULN) and direct bilirubin > 2 x ULN
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  • Inadequate renal function defined by serum creatinine clearance /estimated clearance of ≤ 20(ml/min).
  • History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  • Subjects with CNS involvement.
  • Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 15 days prior to leukapheresis for CAR T-cell manufacture, or is currently enrolled in an investigational study. However, prior therapy with belantamab mafotodin can be used.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Hila Magen, MD contact

+97235308176

Hila.magen@sheba.health.gov.il

Israel1 site, 1 recruiting

  • Chaim Sheba Medical Center, Tel Hashomer

    Ramat Gan, 5262000

    Hila Magen, MD, +9725308176, Hila.Magen@sheba.health.gov.il

    Recruiting

Other trials in Israel

About this study

Official title: A Phase 1/2, Open-Label, Dose Escalation and Confirmation Study of CAR-BCMA, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Multiple Myeloma

This is an open label, abbreviated (3+3) dose escalation study in subjects with RRMM, followed by an extension phase at the selected safe dose. The dose escalation stage will involve recruitment of 3 RRMM patients for 'low' dose (6 x 106 CAR-T cells/kg) CAR-T therapy. After 14 days of follow-up for each of the 3 subjects, the DSC will determine whether the next subject can be recruited.

After 14 days follow-up for the 3rd subject, DSC will review data for the 3rd subject and consider the data for the first 3 subjects. In the absence of dose limiting toxicities (DLTs), the DSC may recommend recruitment of 3 subjects to be treated with the 'high' dose (9x106 CAR-T cells/kg) CAR-T therapy, with similar staggering. In case of DLTs in one of the 3 low dose subjects, the DSC may recommend to recruit an additional 3 low dose subjects (6 in total). If there are no additional DLTs in these 3 patients the low dose may be recommended by the DSC for the extension stage. However, further DLTs may prompt the DSC to recommend to modify the protocol, or to stop the study. In case of DLTs in one of the first 3 high dose subjects, the DSC may recommend to recruit an additional 3 high dose subjects.If there are no additional DLTs in these 3 patients, the high dose may be recommended by the DSC for the study extension stage. However, further DLTs may prompt the DSC to recommend continuation to the extension stage with the low dose, or to modify the protocol, or to stop the study.

Read more

After completion of two months follow-up for the 6th subject in the low or high dose cohort (as applicable), and review of all the data for all subjects, following DSC recommendations, the Stage 2 extension phase of the study may recruit additional subjects, up to a maximum of 75 subjects for Stages 1 and 2, combined.

DSC will review study data during the extension stage follow-up after 5 years to determine if additional safety follow-up is required.

Being tested
CAR-BCMA
Medical subject headings
Multiple Myeloma

What participants receive

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

  • CAR-BCMABiological

    CAR-BCMA T-cells are genetically modified autologous T-cells directed to the B-cell maturation antigen (BCMA). CAR-BCMA T-cells identify and eliminate BCMA-expressing malignant plasma cells. Upon binding to BCMA-expressing cells, the CAR transmits a signal to promote T cell expansion, activation, persistence and elimination of malignant plasma cells.

Study groups in NCT05243212
Study groupRoleWhat they receive
'low' doseExperimentalThe dose escalation stage will involve recruitment of 3 RRMM patients for 'low' dose (6 x 106 CAR-T cells/kg) CAR-T therapy. After 14 days of follow-up for each of the 3 subjects, the DSC will determine whether the next subject can be recruited. After 14 days follow-up for the 3rd subject, DSC will review data for the 3rd subject and consider the data for the first 3 subjects.
Receives: Biological: CAR-BCMA
'high' doseExperimentalIn the absence of dose limiting toxicities (DLTs), the DSC may recommend recruitment of 3 subjects to be treated with the 'high' dose (9x106 CAR-T cells/kg) CAR-T therapy, with similar staggering.
Receives: Biological: CAR-BCMA

What is being measured

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

  1. Overall response rate

    Overall response rate, two months after CAR-BCMA T-cell infusion determined in accordance with the International Myeloma Working Group (IMWG) guidance.

    Measured: 2 months

  2. CAR BCMA related toxicity

    Frequency of CAR-BCMA related toxicities: CRS and ICANS, according to ASTCT consensus grading (Lee 2019).

    Measured: 2 years

  3. CAR BCMA related toxicity

    Any AEs according to common Terminology Criteria for Adverse Events (CTCAE) version 5.0

    Measured: 2 years

Secondary outcomes (2)

  1. progression free survival

    PFS is defined as the time CAR T -cell infusion to the date of either first documented relapse, progression or death due to any cause.

    Measured: 12 months

  2. overalll free survival

    OS was defined as the time from CART-cell infusion to death of any cause

    Measured: 12 months

Timeline

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

  1. First posted16 Feb 2022
  2. Study start19 Sep 2021
  3. Primary completion1 Sep 2024 (estimated)
  4. Study completion1 Sep 2028 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
The treatment dose is 6 or 9 x 10\^6 CAR+ T cells/kg of recipient bodyweight.
Masking
None (open label)
Enrolment
75 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05243212
Sponsor's protocol ID
SHEBA-21-8048-HM-CTIL
Status last verified
Jan 2024
First submitted
11 Oct 2021
Last updated
31 Jan 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CAR-BCMA in people with Multiple Myeloma and Relapse Multiple Myeloma, run by Sheba Medical Center at 1 site in Israel.

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 25 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 31 Jan 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 Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

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

What does this combined phase mean?

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

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Hila Magen, MD (+97235308176, Hila.magen@sheba.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (time frame: 2 months). The study lists 3 primary outcomes in all. 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 NCT05243212.

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 31 Jan 2024.

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