Ciltacabtagene Autoleucel in High-Risk Smoldering Multiple Myeloma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorPETHEMA Foundation
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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).
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.
Disqualifiers
Noninvasive cervical cancer treated within the last 24 months that is considered completely cured.
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).
Trial design
Design model
Single group
Treatments tested in this trial
Group 1: Dara-VRD followed by apheresis and cilta-cel infusion
DrugIn 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 infusion
DrugIn 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.
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: Dara_VRD plus cilta-celExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
5 Years2
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.
Time frame
5 Years3
Safety laboratory tests Immunoglobulin
To measure the Immunoglobulin (Ig) G levels. The units of measure for the immunoglobulin levels determinations will be g/L.
Time frame
5 years4
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.
Time frame
5 yearsSecondary outcomes
1
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.
Time frame
5 Years2
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.
Time frame
5 Years3
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.
Time frame
5 YearsSponsors and contacts
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Source ClinicalTrials.gov