High Risk Smoldering Multiple MyelomaPhase 2CAR-HiRiSMMNCT06574126
Ciltacabtagene Autoleucel in High-Risk Smoldering Multiple Myeloma
A Phase 2 study testing Group 1: Dara-VRD followed by apheresis and cilta-cel infusion and Group 2: Apheresis followed by Dara-VRD and cilta-cel infusion in people with High Risk Smoldering Multiple Myeloma, run by PETHEMA Foundation at 1 site in Spain.
Trial summary
This is an open-label, single arm, multicenter, interventional study with Dara-VRD followed by cilta-cel in high-risk smoldering multiple myeloma (SMM) patients. The primary objectives of this trial, related with efficafy and safety of the treatment, are i) to evaluate the proportion of high-risk SMM patients with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High Risk Smoldering Multiple Myeloma
- What is being tested?
- Group 1: Dara-VRD followed by apheresis and cilta-cel infusion and Group 2: Apheresis followed by Dara-VRD and cilta-cel infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSpain
- Study dates
- 30 Sep 2024to 30 Sep 2032
- Phase
- Phase 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
- Be ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
- High-risk SMM defined as having 1 of the following 2 criteria: i) High-risk per "Mayo 20-2-20" criteria defined as presence of any ≥2 of the following:
- Serum M-protein ≥2 gm/dL
- Involved to uninvolved FLC ratio ≥20
- BMPC % ≥20% to <40% OR ii) Presence of ≥95% of BMPC with an aberrant phenotype within the BMPC compartment and immunoparesis present defined as a reduction of at least 25% below the lower normal limit for ≥1 uninvolved immunoglobulin isotype (only IgG, IgA and IgM will be considered).
- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1.
Show all 23Show fewer
- Have an estimated glomerular filtration rate (eGFR), based on the Modified Diet in Renal Disease (MDRD) 4-variable formula or 24-hour urine collection of ≥40 mL/min during the screening period.
- Laboratory values obtained <21 days prior to Screening: i) Total bilirubin ≤2.0 mg/dL ii) Aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) iii) Alanine transaminase (ALT) ≤3 x ULN
- Hemoglobin ≥8.0 g/dL (≥5 mmol/L) (without prior red blood cell [RBC] transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted). For subjects who meet the inclusion criteria at screening, transfusion of RBCs is permitted after screening as needed to maintain a hemoglobin level ≥8.0 g/dL.
- Neutrophils ≥1.0 × 109/L (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test)
- Platelets ≥75 × 109/L (must be without transfusion support in the 7 days prior to the laboratory test)
- Lymphocyte count ≥0.3*109/L
- Participants should be seronegative for human immunodeficiency virus (HIV) or have controlled disease if seropositive.
- A female participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study.
- A female participant must be either of the following: i) Not of childbearing potential ii) Of childbearing potential and practicing at least 1 highly effective method of contraception throughout the study and through 6 months after the last dose of study treatment. If a female participant becomes of childbearing potential after the start of the study, the female participant must comply with ii).
- A female participant using oral contraceptives should use an additional barrier contraceptive method.
- A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after receiving the cilta-cel infusion. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility.
- A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 1 year after receiving the cilta-cel infusion. If the male participant's partner is a female of childbearing potential, the male participant must use condoms (with or without spermicide) and the female partner of the male participant must also be practicing a highly effective method of contraception. A male participant who is vasectomized must still use a condom (with or without spermicide), but the partner is not required to use contraception.
- A male participant must agree not to donate sperm for the purposes of reproduction during the study and for 1 year after receiving the last dose of study treatment. Male participants should consider preservation of sperm prior to study treatment as anti-cancer treatments may impair fertility.
- A male participant must agree not to plan to father a child while enrolled in this study or within 1 year after the last dose of study treatment.
- Must sign an informed consent form (ICF) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study
- An additional ICF will be collected to get participants authorization to collect the necessary samples for performing the Biological studies indicated in this protocol.
- Be willing and able to adhere to the lifestyle restrictions specified in this protocol.
Who cannot join
- History of uncontrolled illness, including but not limited to MGUS, standard risk smoldering myeloma, active myeloma by current IMWG definition, light chain amyloidosis with organ involvement or patients with extramedullary disease.
- Non-muscle-invasive bladder cancer treated within the last 24 months that is considered completely cured.
- Skin cancer (nonmelanoma or melanoma) treated within the last 24 months that is considered completely cured.
- Noninvasive cervical cancer treated within the last 24 months that is considered completely cured.
- Localized prostate cancer (N0M0):
- with a Gleason score ≤6, treated within the last 24 months or untreated and under surveillance.
Show all 25Show fewer
- with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence.
- history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence).
- Adequately treated lobular carcinoma in situ or ductal carcinoma in situ.
- History of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence.
- Known allergies, hypersensitivity, or intolerance to cilta-cel or its excipients.
- Participant had major surgery or had significant traumatic injury ≤14 days prior to Cycle1Day1.
- If any of the following exist at screening, participant will be excluded because this trial involves an investigational agent whose genotoxic, mutagenic, and teratogenic effect on the developing fetus and newborn are unknown:
- Pregnant women ii) Nursing women iii) Men or women of childbearing potential who are unwilling to employ adequate contraception
- Other comorbidity which would interfere with subject's ability to participate in trial, eg, uncontrolled infection, uncompensated heart, or lung disease.
- Any medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- History of neurodegenerative disease (eg, Parkinson or stroke within 6 months).
- Medical history of treatment for another malignancy <2 years before trial enrollment, other concurrent chemotherapy, or any ancillary therapy considered investigational. Note: Bisphosphonates are considered supportive care rather than therapy and are thus allowed while on protocol treatment.
- Known seropositive for or active viral infection with HIV, HBV, hepatitis C virus (HCV), or SARS-CoV-2 (Coronavirus Disease 2019 [COVID-19]).
- Participants who are positive for SARS-COV-2 antibody, HIV1 and 2 antibody, hepatitis B core antibody (HBc), or hepatitis B surface antigen (HBsAg) must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
- Participants who are positive for HIV1 or 2 infections, with undetectable viral load and on stable antiretrovirals, will not be excluded.
- Participants with past HCV infection need at least 12 months of sustained virologic response and be negative for RNA to enter.
- Patients with a high-risk of HBV reactivation (eg, negative for HBV antigen but positive for chronic HBV, with or without anti-serum HBV) must be monitored with DNA and ALT/AST).
- Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
- NOTE: Investigators must ensure that all study enrollment criteria have been met at screening. If a participant's clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of study intervention is given such that the participant no longer meets all eligibility criteria, then the participant must be excluded from participation in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Jesús San Miguel contact
Spain1 site, 1 recruiting
- Recruiting
Hospital Clinico Universitario Salamanca
Salamanca, 37007
Mª Victoria Mateos, Dr, mvmateos@usal.es
About this study
Official title: Phase II Open-Label, Single Arm, Multicenter Study of Ciltacabtagene Autoleucel in High-Risk Smoldering Multiple Myeloma (GEM-CAR-HiRiSMM)
This is an open-label, single arm, multicenter, interventional study with Dara-VRD followed by cilta-cel in high-risk smoldering multiple myeloma (SMM) patients.
The primary objectives of this trial, related with efficafy and safety of the treatment, are i) to evaluate the proportion of high-risk SMM patients with undetectable minimal residual disease (MRD) at 6 months, 12 months, and thereafter every 12 months up to 5 years after cilta-cel administration as well as the sustained undetectable MRD rate in the intent-to-treat (ITT) population; ii) to annotate frequency and severity of adverse events (AE) and serious adverse events (SAE), as well as data from laboratory tests aslo related with safety such as Immunoglobulin (Ig) G levels, complete blood count (CBC) cytopenia adn T-cell populations. Secondary objectives are related with response to therapy and will measure different categories of response and survival.
Read the detailed description
This is an open-label, single arm, multicenter, interventional study with Dara-VRD followed by cilta-cel in high-risk smoldering multiple myeloma (SMM) patients. JNJ-68284528 (ciltacabtagene autoleucel [cilta-cel]) is an autologous chimeric antigen receptor T cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA), a molecule expressed on the surface of mature B-lymphocytes and malignant plasma cells (PCs).
Since the immune system is less impaired in early stages of the disease, high-risk SMM would represent the ideal platform to evaluate the potential of Dara-VRD followed by cilta-cel as a curative approach in high-risk SMM. Study participants will be assigned into 2 groups. Participants in Group 1 will receive a maximum of 2 cycles of Dara-VRD induction therapy followed by apheresis and infusion of cilta-cel. Participants in Group 2 will undergo apheresis followed by Dara-VRD induction and cilta-cel infusion.
The primary objective is to assess the efficacy and safety of Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (Dara-VRD) followed by cilta-cel in high-risk SMM. The endpoints for the primary objective will be:
- To evaluate the proportion of high-risk SMM patients with undetectable minimal residual disease (MRD) at 6 months, 12 months, and thereafter every 12 months up to 5 years after cilta-cel administration as well as the sustained undetectable MRD rate in the intent-to-treat (ITT) population. MRD will be evaluated in the bone marrow by Next Generation Flow and Next Generation Sequencing with sensitivity level of 10-5.
- Nature, frequency, severity, and timing of adverse events (AEs), discontinuations due to AEs, and serious adverse events (SAEs).
- Selected safety laboratory test: Immunoglobulin (Ig) G levels, complete blood count (CBC) cytopenia, and cluster of differentiation 4 (CD4+) T lymphocytes (T cells).
The key secondary objectives are:
- To further evaluate the efficacy of Dara-VRD followed by cilta-cel in high-risk SMM patients as measured by ORR as well as different response categories partial response (PR), very good partial response (VGPR), complete response (CR), and stringent CR (sCR), and duration of response (DOR).
- To assess the survival (OS) and progression free survival (PFS) of patients with high-risk SMM.
- Conditions
- High Risk Smoldering Multiple Myeloma
- Being tested
- Group 1: Dara-VRD followed by apheresis and cilta-cel infusion, Group 2: Apheresis followed by Dara-VRD and cilta-cel infusion
- Keywords
- Smoldering Multiple Myoloma, CAR T-cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Group 1: Dara-VRD followed by apheresis and cilta-cel infusionDrug
In Group 1, 10 eligible participants will undergo a maximum of two 28-day induction cycles with Dara-VRD. Participants in Group 1 are considered enrolled as the date of signing the Informed Consent Form. This will be followed by apheresis according to institutional standards with the collection target and instructions for processing and shipping apheresis product provided in the Cell Therapy Investigational Product Procedures Manual. Cilta-cel will be generated from T cells selected from the apheresis. Participants for whom apheresis or manufacturing fails will be allowed a second attempt of apheresis. Between apheresis and cilta-cel infusion, participants will be allowed to have stem cell collection using GCSF+/-plerixafor. Cilta-cel will be manufactured by transduction of T cells with an LV vector expressing anti-BCMA CAR, followed by T cell expansion.
Group 2: Apheresis followed by Dara-VRD and cilta-cel infusionDrug
In Group 2, 10 eligible participants will undergo apheresis first, according to institutional standards with the collection target and instructions for processing and shipping apheresis product provided in the Cell Therapy Investigational Product Procedures Manual. Study enrollment is defined as the date of signing Informed Consent Form. The apheresis will be followed by a maximum of two 28-day induction cycles with DARA-VRD. Cilta-cel will be generated from T cells selected from the apheresis. Participants for whom the apheresis or manufacturing fails will be allowed a second attempt at apheresis. Between apheresis and cilta-cel infusion, participants will be allowed to have stem cell collection using GCSF+/-plerixafor. Cilta-cel will be manufactured by transduction of T cells with an LV vector expressing anti-BCMA CAR, followed by T cell expansion.
| Study group | Role | What they receive |
|---|---|---|
| Dara_VRD plus cilta-cel | Experimental | Study participants will be assigned to either Group 1 (n=10) or Group 2 (n=10), depending on cilta-cel manufacturing availability. Participants in Group 1 will receive a maximum of 2 cycles of Dara-VRD induction therapy followed by apheresis and infusion of cilta-cel. Participants in Group 2 will undergo apheresis followed by 2 cycles of Dara-VRD induction therapy and cilta-cel infusion with the objective of evaluating changes in the quantity and quality of T cells collected. Receives: Drug: Group 1: Dara-VRD followed by apheresis and cilta-cel infusion; Drug: Group 2: Apheresis followed by Dara-VRD and cilta-cel infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with undetectable minimal residual disease (MRD)
To evaluate the proportion of high-risk SMM patients with undetectable minimal residual disease (MRD) at 6 months, 12 months, and thereafter every 12 months up to 5 years after cilta-cel administration as well as the sustained undetectable MRD rate in the intent-to-treat (ITT) population. MRD will be evaluated in the bone marrow by Next Generation Flow and Next Generation Sequencing with sensitivity level of 10-5. Undetectable MRD is defined as <0,001% of bone marrow MM plasma cells/bone marrow normal plasma cells.
Measured: 5 Years
Adverse events
To annotate the nature, frequency, severity, and timing of adverse events (AEs) and serious adverse events (SAEs), and discontinuations due to AEs or SAEs.
Measured: 5 Years
Safety laboratory tests Immunoglobulin
To measure the Immunoglobulin (Ig) G levels. The units of measure for the immunoglobulin levels determinations will be g/L.
Measured: 5 years
Safety laboratory tests CBC
To measure the complete blood count (CBC) cytopenia. The units of measure for the CBC determinations will be cells*109/L.
Measured: 5 years
Safety laboratory tests T-cells
To measure the cluster of differentiation 4 (CD4+) T lymphocytes (T-cells). The units of measure for the immunoglobulin levels determinations of will be cells*109/L.
Measured: 5 years
Secondary outcomes (3)
Response rate
To evaluate the overall response rate (ORR) as well as different response categories partial response (PR), very good partial response (VGPR), complete response (CR), and stringent CR (sCR), and duration of response (DOR), according to clinical judgement guided by the International Myeloma Working Group (IMWG) consensus recommendations for multiple myeloma treatment response criteria.
ORR is defined as the proportion of subjects who achieve a partial response (PR) or better according to the IMWG criteria after infusion of cilta-cel.
Measured: 5 Years
Overall Survival
To assess the survival (OS) of patients with high-risk SMM. OS is defined as the time from the date of the initial infusion of cilta-cel to the date of the subject's death. If the subject is alive or the vital status is unknown, then the subject's data will be censored at the date the subject was last known to be alive.
Measured: 5 Years
Progression-Free Survival
To assess progression free survival (PFS) of patients with high-risk SMM. PFS is defined as the time from the date of the first administration of study treatment to the date of first documented disease progression to myeloma defining events, as defined in the IMWG criteria, or death due to any cause, whichever occurs first. For subjects who have not progressed and are alive, data will be censored at the last disease evaluation before the start of any subsequent anti-myeloma therapy.
Measured: 5 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2024
- Study start30 Sep 2024
- Primary completion30 Sep 2032 (estimated)
- Study completion30 Sep 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Risk Smoldering 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase II Open-Label, Single Arm, Multicenter Study in which all patients with receive Dara-VRD and cilta-cel therapy
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PETHEMA Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Juan José Lahuerta, Study chair, Hospital 12 de OctubreJoan Bladé, Study chair, Hospital Clinic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06574126
- Sponsor's protocol ID
- GEM-CAR-HiRiSMM
- Acronym
- CAR-HiRiSMM
- Status last verified
- Oct 2024
- First submitted
- 23 Aug 2024
- Last updated
- 26 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: All participant data relating to the study will be recorded on electronic CRF unless transmitted to the sponsor or designee electronically (e.g., laboratory data). The investigator is responsible for verifying that data entries are accurate and correct by physically or electronically signing the eCRF. Results of this clinical trial, positive or negative, will be presented at scientific conferences and published in scientific journals.
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Open-Label, Single Arm, Multicenter Study of Ciltacabtagene Autoleucel in High-Risk Smoldering Multiple Myeloma (GEM-CAR-HiRiSMM)
- ClinicalTrials.gov ID
- NCT06574126
- Acronym / sponsor ID
- CAR-HiRiSMM / GEM-CAR-HiRiSMM
- Conditions
- High Risk Smoldering Multiple Myeloma
- Keywords
- Smoldering Multiple Myoloma, CAR T-cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- PETHEMA FoundationUniversity, hospital or other
- Study start
- 30 Sep 2024 (actual)
- Primary completion
- 30 Sep 2032 (estimated)
- Study completion
- 30 Sep 2032 (estimated)
- First posted
- 27 Aug 2024 (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.
This is an open-label, single arm, multicenter, interventional study with Dara-VRD followed by cilta-cel in high-risk smoldering multiple myeloma (SMM) patients.
The primary objectives of this trial, related with efficafy and safety of the treatment, are i) to evaluate the proportion of high-risk SMM patients with undetectable minimal residual disease (MRD) at 6 months, 12 months, and thereafter every 12 months up to 5 years after cilta-cel administration as well as the sustained undetectable MRD rate in the intent-to-treat (ITT) population; ii) to annotate frequency and severity of adverse events (AE) and serious adverse events (SAE), as well as data from laboratory tests aslo related with safety such as Immunoglobulin (Ig) G levels, complete blood count (CBC) cytopenia adn T-cell populations. Secondary objectives are related with response to therapy and will measure different categories of response and survival.
Detailed description
This is an open-label, single arm, multicenter, interventional study with Dara-VRD followed by cilta-cel in high-risk smoldering multiple myeloma (SMM) patients. JNJ-68284528 (ciltacabtagene autoleucel [cilta-cel]) is an autologous chimeric antigen receptor T cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA), a molecule expressed on the surface of mature B-lymphocytes and malignant plasma cells (PCs).
Since the immune system is less impaired in early stages of the disease, high-risk SMM would represent the ideal platform to evaluate the potential of Dara-VRD followed by cilta-cel as a curative approach in high-risk SMM. Study participants will be assigned into 2 groups. Participants in Group 1 will receive a maximum of 2 cycles of Dara-VRD induction therapy followed by apheresis and infusion of cilta-cel. Participants in Group 2 will undergo apheresis followed by Dara-VRD induction and cilta-cel infusion.
The primary objective is to assess the efficacy and safety of Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (Dara-VRD) followed by cilta-cel in high-risk SMM. The endpoints for the primary objective will be:
- To evaluate the proportion of high-risk SMM patients with undetectable minimal residual disease (MRD) at 6 months, 12 months, and thereafter every 12 months up to 5 years after cilta-cel administration as well as the sustained undetectable MRD rate in the intent-to-treat (ITT) population. MRD will be evaluated in the bone marrow by Next Generation Flow and Next Generation Sequencing with sensitivity level of 10-5.
- Nature, frequency, severity, and timing of adverse events (AEs), discontinuations due to AEs, and serious adverse events (SAEs).
- Selected safety laboratory test: Immunoglobulin (Ig) G levels, complete blood count (CBC) cytopenia, and cluster of differentiation 4 (CD4+) T lymphocytes (T cells).
The key secondary objectives are:
- To further evaluate the efficacy of Dara-VRD followed by cilta-cel in high-risk SMM patients as measured by ORR as well as different response categories partial response (PR), very good partial response (VGPR), complete response (CR), and stringent CR (sCR), and duration of response (DOR).
- To assess the survival (OS) and progression free survival (PFS) of patients with high-risk SMM.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase II Open-Label, Single Arm, Multicenter Study in which all patients with receive Dara-VRD and cilta-cel therapy
| Arm | Type | Receives |
|---|---|---|
| Dara_VRD plus cilta-cel | Experimental | Drug: Group 1: Dara-VRD followed by apheresis and cilta-cel infusion, Drug: Group 2: Apheresis followed by Dara-VRD and cilta-cel infusionStudy participants will be assigned to either Group 1 (n=10) or Group 2 (n=10), depending on cilta-cel manufacturing availability. Participants in Group 1 will receive a maximum of 2 cycles of Dara-VRD induction therapy followed by apheresis and infusion of cilta-cel. Participants in Group 2 will undergo apheresis followed by 2 cycles of Dara-VRD induction therapy and cilta-cel infusion with the objective of evaluating changes in the quantity and quality of T cells collected. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Be ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
- High-risk SMM defined as having 1 of the following 2 criteria: i) High-risk per "Mayo 20-2-20" criteria defined as presence of any ≥2 of the following:
- Serum M-protein ≥2 gm/dL
- Involved to uninvolved FLC ratio ≥20
- BMPC % ≥20% to <40% OR ii) Presence of ≥95% of BMPC with an aberrant phenotype within the BMPC compartment and immunoparesis present defined as a reduction of at least 25% below the lower normal limit for ≥1 uninvolved immunoglobulin isotype (only IgG, IgA and IgM will be considered).
Key exclusion criteria (25 listed)
- NOTE: Investigators must ensure that all study enrollment criteria have been met at screening. If a participant's clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of study intervention is given such that the participant no longer meets all eligibility criteria, then the participant must be excluded from participation in the study.
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 |
|---|---|---|
| Group 1: Dara-VRD followed by apheresis and cilta-cel infusionIn Group 1, 10 eligible participants will undergo a maximum of two 28-day induction cycles with Dara-VRD. Participants in Group 1 are considered enrolled as the date of signing the Informed Consent Form. This will be followed by apheresis according to institutional standards with the collection target and instructions for processing and shipping apheresis product provided in the Cell Therapy Investigational Product Procedures Manual. Cilta-cel will be generated from T cells selected from the apheresis. Participants for whom apheresis or manufacturing fails will be allowed a second attempt of apheresis. Between apheresis and cilta-cel infusion, participants will be allowed to have stem cell collection using GCSF+/-plerixafor. Cilta-cel will be manufactured by transduction of T cells with an LV vector expressing anti-BCMA CAR, followed by T cell expansion. | Drug | Dara_VRD plus cilta-cel |
| Group 2: Apheresis followed by Dara-VRD and cilta-cel infusionIn Group 2, 10 eligible participants will undergo apheresis first, according to institutional standards with the collection target and instructions for processing and shipping apheresis product provided in the Cell Therapy Investigational Product Procedures Manual. Study enrollment is defined as the date of signing Informed Consent Form. The apheresis will be followed by a maximum of two 28-day induction cycles with DARA-VRD. Cilta-cel will be generated from T cells selected from the apheresis. Participants for whom the apheresis or manufacturing fails will be allowed a second attempt at apheresis. Between apheresis and cilta-cel infusion, participants will be allowed to have stem cell collection using GCSF+/-plerixafor. Cilta-cel will be manufactured by transduction of T cells with an LV vector expressing anti-BCMA CAR, followed by T cell expansion. | Drug | Dara_VRD plus cilta-cel |
Primary outcome
Proportion of patients with undetectable minimal residual disease (MRD)
Time frame: 5 Years
To evaluate the proportion of high-risk SMM patients with undetectable minimal residual disease (MRD) at 6 months, 12 months, and thereafter every 12 months up to 5 years after cilta-cel administration as well as the sustained undetectable MRD rate in the intent-to-treat (ITT) population. MRD will be evaluated in the bone marrow by Next Generation Flow and Next Generation Sequencing with sensitivity level of 10-5. Undetectable MRD is defined as <0,001% of bone marrow MM plasma cells/bone marrow normal plasma cells.
Adverse events
Time frame: 5 Years
To annotate the nature, frequency, severity, and timing of adverse events (AEs) and serious adverse events (SAEs), and discontinuations due to AEs or SAEs.
Safety laboratory tests Immunoglobulin
Time frame: 5 years
To measure the Immunoglobulin (Ig) G levels. The units of measure for the immunoglobulin levels determinations will be g/L.
Safety laboratory tests CBC
Time frame: 5 years
To measure the complete blood count (CBC) cytopenia. The units of measure for the CBC determinations will be cells*109/L.
Safety laboratory tests T-cells
Time frame: 5 years
To measure the cluster of differentiation 4 (CD4+) T lymphocytes (T-cells). The units of measure for the immunoglobulin levels determinations of will be cells*109/L.
3 secondary outcomes
Response rate
Time frame: 5 Years
Overall Survival
Time frame: 5 Years
Progression-Free Survival
Time frame: 5 Years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2024.
- Individual participant dataSharing planned: No. All participant data relating to the study will be recorded on electronic CRF unless transmitted to the sponsor or designee electronically (e.g., laboratory data). The investigator is responsible for verifying that data entries are accurate and correct by physically or electronically signing the eCRF. Results of this clinical trial, positive or negative, will be presented at scientific conferences and published in scientific journals.
Related trials for High Risk Smoldering Multiple Myeloma
RecruitingPhase 3
A Study to Compare Linvoseltamab and Daratumumab Treatment in High-Risk Smoldering Multiple Myeloma (HR-SMM)
High Risk Smoldering Multiple Myeloma (HR-SMM)
RecruitingPhase 2
Isatuximab and Iberdomide as Immunotherapy for High Risk in Smouldering Myeloma
Smouldering Myeloma
Active, not recruitingPhase 2
Isatuximab With or Without Lenalidomide in Patients With High Risk Smoldering Multiple Myeloma (ISAMAR)
Smoldering Plasma Cell Myeloma
Active, not recruitingPhase 3
Lenalidomide or Observation in Treating Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma
Light Chain Deposition Disease, Smoldering Multiple Myeloma
RecruitingPhase 1
A Study of JNJ-79635322 in Combination With Daratumumab With or Without Lenalidomide for Multiple Myeloma, Newly Diagnosed AL Amyloidosis, and High-risk Smoldering Multiple Myeloma or JNJ-79635322 in Combination With Pomalidomide for Multiple Myeloma
Multiple Myeloma, Smoldering Multiple Myeloma
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.
Jesús San Miguel contact
Juan José Lahuerta study chair
Hospital 12 de Octubre
Joan Bladé study chair
Hospital Clinic of Barcelona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Group 1: Dara-VRD followed by apheresis and cilta-cel infusion and Group 2: Apheresis followed by Dara-VRD and cilta-cel infusion in people with High Risk Smoldering Multiple Myeloma, run by PETHEMA Foundation at 1 site in Spain.
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 23 inclusion and 25 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 26 Oct 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 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 phase mean?
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 María-Victoria Mateos (+34 923 291 100, mvmateos@usal.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with undetectable minimal residual disease (MRD) (time frame: 5 Years). The study lists 5 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 26 Oct 2024.