Multiple MyelomaPhase 1/2NCT04499339
A Phase I/IIa Clinical Trial to Assess Feasibility, Safety and Antitumor Activity of Autologous SLAMF7 CAR-T Cells in Multiple Myeloma
A Phase 1/2 study testing SLAMF7 CAR-T in people with Multiple Myeloma, run by Wuerzburg University Hospital at 3 sites in 3 countries.
Trial summary
Multiple myeloma (MM) is a rare hematologic malignancy of aberrant plasma cells. There is a high and currently unmet medical need for novel, innovative treatment concepts to improve the therapeutic outcome and prognosis of patients suffering from MM. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- SLAMF7 CAR-T
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 22 Jul 2020to Dec 2025
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent form.
- Patient is ≥18 years of age.
- Patient is willing and able to adhere to the protocol requirements.
- Patient with diagnosis of MM who has been treated with at least 2 prior lines of treatment, including at least one cycle of high-dose chemotherapy with autologous hematopoietic stem cell transplantation if the patient was eligible, and exposure to an immunomodulatory imide drug (e.g. lenalidomide and/or pomalidomide), a proteasome inhibitor, and an anti-CD38 antibody.
- (Note: Induction therapy, up to 2 cycles of high-dose chemotherapy with autologous hematopoietic stem cell transplantation, and subsequent consolidation and/or maintenance therapy are considered one line of treatment).
- At least one of the following subcriteria must be measured in the patient:
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- Serum M-protein greater or equal to 0.5 g/dL
- Urine M-protein greater or equal to 200 mg/24 h
- Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal
- A biopsy-proven evaluable plasmacytoma
- Bone marrow plasma cells >10% of total bone marrow cells (>30% if bone marrow plasma cells are the only marker of measurable disease)
- Patients previously treated with an anti-SLAMF7 antibody are eligible.
- Karnofsky performance status ≥60%. If patient has a Karnofsky performance status <60% (e.g. after a spinal cord injury) but is judged to be medically fit by the investigator, patient is eligible.
- Female patients of childbearing potential must:
- have a negative pregnancy test (blood) at screening.
- either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective measures of contraception without interruption, from screening through 1 year following the investigantional medicinal product (IMP) infusion. A highly effective method of contraception or birth control (failure rate less than 1% per year when used consistently and correctly) must be practiced. The patient should be informed of the potential risks associated with becoming pregnant while enrolled in this clinical trial. Reliable methods for this trial are: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence or vasectomized sexual partner. Abstinence is only accepted as true abstinence: when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods and withdrawal] are not acceptable methods of contraception.) Postmenopausal (no menses for at least 1 year without alternative medical cause) or surgically sterile female patients (tubal ligation, hysterectomy or bilateral oophorectomy) may be enrolled.
- Agree to abstain from breast feeding during the study participation and for 1 year after the IMP infusion.
- Male patients must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for at least 1 year after IMP infusion, even if he has undergone a successful vasectomy.
Who cannot join
- Patient has undergone a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤12 months prior to leukapheresis.
- Patient has undergone a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning >12 months, and suffers on chronic Graft-versus-Host Disease and/or is on systemic immune-suppressants.
- Patient with diagnosis of MM
- in first relapse following an autologous stem cell transplantation or
- in second relapse that subsequently achieves a complete response that is considered being a candidate for an allogeneic stem cell transplantation, unless the patient explicitly denies undergoing an allogeneic stem cell transplantation.
- Patient has received anti-CD38 and/or anti-SLAMF7 antibodies ≤8 weeks prior to leukapheresis.
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- Ongoing treatment with systemic immune-suppressants (e.g. systemic cyclosporine or systemic steroids at any dose).
- (Note: Physiologic steroid replacement therapy, topical immune-suppressants as e.g. cyclosporine/tacrolimus eye drops and topical steroids are permitted.)
- Echocardiogram with left ventricular ejection fraction <45%.
- Inadequate renal function defined by creatinine clearance (CrCl) ≤45 mL/min using Cockcroft-Gault equation.
- Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x upper limit of normal (ULN) and total bilirubin >1.5 x ULN (unless due to Gilbert's syndrome and direct bilirubin is ≤1.5 x ULN; unless due to intrahepatic myeloma lesions as demonstrated by MRI or positron emission tomography (PET)/computed tomography (CT) not older than 4 weeks prior to screening).
- International ratio (INR) or partial thromboplastin time (PTT) >1.5 x ULN, unless on a stable dose of anti-coagulant.
- Evidence of human immunodeficiency virus (HIV) infection.
- Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV), excluding
- Patients who are hepatitis B surface antigen negative and HBV viral DNA negative
- Patients who had hepatitis B but have received an antiviral treatment and show non-detectable viral DNA for 6 months
- Patients who are seropositive because of hepatitis B virus vaccine
- Patients with known HBV infection but undetectable HBV viral load and on anti-viral therapy to prevent HBV reactivation.
- Seropositive for and with active viral infection with hepatitis C virus (HCV), excluding
- Patients who had hepatitis C but had received an antiviral treatment and show no detectable HCV viral RNA for 6 months.
- Seropositive for syphilis on treponema pallidum hemagglutination test, excluding
- Patients with negative treponema pallidum antibody absorption test result
- Patients with active infection (e.g. asymptomatic and symptomatic severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) or other serious medical or psychiatric disorder on investigators decision.
- Pregnant or lactating women.
- Current or previous (within 30 days of enrollment) treatment with another IMP.
- Known abuse of alcohol, drugs, or medicinal products.
- Employees of the sponsor, or employees or relatives of the investigator.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
Germany1 site
Early Clinical Trial Unit University Hospital Wuerzburg
Würzburg, 97080
Spain1 site
Clinical Trials Unit, Clinica Universidad de Navarra
Pamplona, Navarre, 31008
About this study
Multiple myeloma (MM) is a rare hematologic malignancy of aberrant plasma cells.
There is a high and currently unmet medical need for novel, innovative treatment concepts to improve the therapeutic outcome and prognosis of patients suffering from MM.
Read more
There is definitive evidence that MM is susceptible to immune-based therapies from pre-clinical investigations and early clinical trials.
CARAMBA-1 is a first-in-human clinical trial of adoptive immunotherapy with autologous signaling lymphocytic activation molecule F7 (SLAMF7) chimeric antigen receptor (CAR)-T cells in patients with advanced MM that have exhausted conventional therapies.
The CARAMBA-1 clinical trial is an open-label, non-randomized, multicenter clinical trial which combines a phase I dose-escalation part with a phase IIa dose-expansion part to assess feasibility, safety and anti-myeloma activity of SLAMF7 CAR-T cells.
The CARAMBA project and the CARAMBA-1 clinical trial are supported by the European Union in the Horizon 2020 research and innovation program.
Read the detailed description
Multiple myeloma (MM) is a rare hematologic malignancy of aberrant plasma cells.
There is a high and currently unmet medical need for novel, innovative treatment concepts to improve the therapeutic outcome and prognosis of patients suffering from MM.
There is definitive evidence that MM is susceptible to immune-based therapies from pre-clinical investigations and early clinical trials.
CARAMBA-1 is a first-in human clinical trial of adoptive immunotherapy with autologous SLAMF7 CAR-T cells in patients with advanced MM that have exhausted conventional therapies.
The CARAMBA-1 clinical trial is an open-label, non-randomized, multicenter clinical trial which combines a phase I dose-escalation part with a phase IIa dose-expansion part to assess feasibility, safety and anti-myeloma activity of SLAMF7 CAR-T cells.
SLAMF7 CAR-T cells are manufactured using virus-free gene-transfer using the Sleeping Beauty transposon system.
The CAR-T cell product is formulated to contain equal proportions of CD8 cytotoxic and CD4 helper SLAMF7 CAR-T cells.
The CARAMBA project and the CARAMBA-1 clinical trial are supported by the European Union in the Horizon 2020 research and innovation program.
- Conditions
- Multiple Myeloma
- Being tested
- SLAMF7 CAR-T
- Keywords
- SLAMF7, Chimeric antigen receptor, CAR, CAR-T cell, immunotherapy, virus-free gene transfer
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SLAMF7 CAR-TDrug
Single infusion of autologous SLAMF7 CAR-T cells
| Study group | Role | What they receive |
|---|---|---|
| All eligible patients | Experimental | Not described Receives: Drug: SLAMF7 CAR-T |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety determination of the treatment with SLAMF7 CAR-T in phase I
Type, frequency and severity of AEs in phase I
Measured: through study completion, an average of 2 years
Determination of the maximum tolerated dose (MTD) and the recommended phase IIa dose of SLAMF7 CAR-T in patients with MM
For the primary endpoint in phase I, the maximum tolerated dose will be determined and recommended for phase IIa.
Measured: through study Phase I completion, an average of 2 years
Safety determination of the treatment with SLAMF7 CAR-T in phases I and IIa
Type, frequency and severity of AEs in phase I and IIa
Measured: through study completion, an average of 2 years
Evaluation of the efficacy, defined as overall response rate (ORR) after treatment with SLAMF7 CAR-T in patients with MM
In Phase IIa the efficacy will be evaluated, defined as ORR.
Measured: through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2020
- Study start22 Jul 2020
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wuerzburg University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- European Union
- Responsible party
- Sponsor
- Investigators
- Prof. Michael Hudecek, Study director, Wuerzburg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04499339
- Sponsor's protocol ID
- CARAMBA-1
- Other IDs
- 2019-001264-30, 2019
- Status last verified
- Apr 2024
- First submitted
- 24 Jul 2020
- Last updated
- 25 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa Clinical Trial to Assess Feasibility, Safety and Antitumor Activity of Autologous SLAMF7 CAR-T Cells in Multiple Myeloma
- ClinicalTrials.gov ID
- NCT04499339
- Acronym / sponsor ID
- CARAMBA-1
- Conditions
- Multiple Myeloma
- Keywords
- SLAMF7, Chimeric antigen receptor, CAR, CAR-T cell, immunotherapy, virus-free gene transfer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- Wuerzburg University HospitalUniversity, hospital or other
- Collaborators
- European Union
- Study start
- 22 Jul 2020 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 5 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multiple myeloma (MM) is a rare hematologic malignancy of aberrant plasma cells.
There is a high and currently unmet medical need for novel, innovative treatment concepts to improve the therapeutic outcome and prognosis of patients suffering from MM.
There is definitive evidence that MM is susceptible to immune-based therapies from pre-clinical investigations and early clinical trials.
CARAMBA-1 is a first-in-human clinical trial of adoptive immunotherapy with autologous signaling lymphocytic activation molecule F7 (SLAMF7) chimeric antigen receptor (CAR)-T cells in patients with advanced MM that have exhausted conventional therapies.
The CARAMBA-1 clinical trial is an open-label, non-randomized, multicenter clinical trial which combines a phase I dose-escalation part with a phase IIa dose-expansion part to assess feasibility, safety and anti-myeloma activity of SLAMF7 CAR-T cells.
The CARAMBA project and the CARAMBA-1 clinical trial are supported by the European Union in the Horizon 2020 research and innovation program.
Detailed description
Multiple myeloma (MM) is a rare hematologic malignancy of aberrant plasma cells.
There is a high and currently unmet medical need for novel, innovative treatment concepts to improve the therapeutic outcome and prognosis of patients suffering from MM.
There is definitive evidence that MM is susceptible to immune-based therapies from pre-clinical investigations and early clinical trials.
CARAMBA-1 is a first-in human clinical trial of adoptive immunotherapy with autologous SLAMF7 CAR-T cells in patients with advanced MM that have exhausted conventional therapies.
The CARAMBA-1 clinical trial is an open-label, non-randomized, multicenter clinical trial which combines a phase I dose-escalation part with a phase IIa dose-expansion part to assess feasibility, safety and anti-myeloma activity of SLAMF7 CAR-T cells.
SLAMF7 CAR-T cells are manufactured using virus-free gene-transfer using the Sleeping Beauty transposon system.
The CAR-T cell product is formulated to contain equal proportions of CD8 cytotoxic and CD4 helper SLAMF7 CAR-T cells.
The CARAMBA project and the CARAMBA-1 clinical trial are supported by the European Union in the Horizon 2020 research and innovation program.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All eligible patients | Experimental | Drug: SLAMF7 CAR-T |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Signed informed consent form.
- Patient is ≥18 years of age.
- Patient is willing and able to adhere to the protocol requirements.
- Patient with diagnosis of MM who has been treated with at least 2 prior lines of treatment, including at least one cycle of high-dose chemotherapy with autologous hematopoietic stem cell transplantation if the patient was eligible, and exposure to an immunomodulatory imide drug (e.g. lenalidomide and/or pomalidomide), a proteasome inhibitor, and an anti-CD38 antibody.
- (Note: Induction therapy, up to 2 cycles of high-dose chemotherapy with autologous hematopoietic stem cell transplantation, and subsequent consolidation and/or maintenance therapy are considered one line of treatment).
Key exclusion criteria (27 listed)
- Patient has undergone a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤12 months prior to leukapheresis.
- Patient has undergone a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning >12 months, and suffers on chronic Graft-versus-Host Disease and/or is on systemic immune-suppressants.
- Patient with diagnosis of MM
- Patient has received anti-CD38 and/or anti-SLAMF7 antibodies ≤8 weeks prior to leukapheresis.
- Ongoing treatment with systemic immune-suppressants (e.g. systemic cyclosporine or systemic steroids at any dose).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SLAMF7 CAR-TSingle infusion of autologous SLAMF7 CAR-T cells | Drug | All eligible patients |
Primary outcome
Safety determination of the treatment with SLAMF7 CAR-T in phase I
Time frame: through study completion, an average of 2 years
Type, frequency and severity of AEs in phase I
Determination of the maximum tolerated dose (MTD) and the recommended phase IIa dose of SLAMF7 CAR-T in patients with MM
Time frame: through study Phase I completion, an average of 2 years
For the primary endpoint in phase I, the maximum tolerated dose will be determined and recommended for phase IIa.
Safety determination of the treatment with SLAMF7 CAR-T in phases I and IIa
Time frame: through study completion, an average of 2 years
Type, frequency and severity of AEs in phase I and IIa
Evaluation of the efficacy, defined as overall response rate (ORR) after treatment with SLAMF7 CAR-T in patients with MM
Time frame: through study completion, an average of 2 years
In Phase IIa the efficacy will be evaluated, defined as ORR.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2024.
- CARAMBA project homepageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prof. Michael Hudecek study director
Wuerzburg University Hospital
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SLAMF7 CAR-T in people with Multiple Myeloma, run by Wuerzburg University Hospital at 3 sites in 3 countries.
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 18 inclusion and 27 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: status not confirmed, as of the sponsor's last update on 25 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France, Germany, Spain. 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?
Results are not available in the source record.
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?
Safety determination of the treatment with SLAMF7 CAR-T in phase I (time frame: through study completion, an average of 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Apr 2024.