Ciltacabtagene Autoleucel in High-Risk Smoldering Multiple Myeloma

NCT06574126 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GEM-CAR-HiRiSMM
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

High Risk Smoldering Multiple Myeloma

Keywords

Smoldering Multiple Myoloma; CAR T-cells

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  5 years

Secondary Outcomes (3)

• Response rate

  5 Years

• Overall Survival

  5 Years

• Progression-Free Survival

  5 Years

Study Arms (1)

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.

Drug: Group 1: Dara-VRD followed by apheresis and cilta-cel infusion; Drug: Group 2: Apheresis followed by Dara-VRD and cilta-cel infusion

Interventions

Group 1: Dara-VRD followed by apheresis and cilta-cel infusion DRUG

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.

Dara_VRD plus cilta-cel

Group 2: Apheresis followed by Dara-VRD and cilta-cel infusion DRUG

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.

Dara_VRD plus cilta-cel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.
• \- 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
• \- 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.

You may not qualify if:

• \- 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):
• i) with a Gleason score ≤6, treated within the last 24 months or untreated and under surveillance.
• ii) 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.
• iii) 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:
• i) 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.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (1)

Hospital Clinico Universitario Salamanca

Salamanca, 37007, Spain

RECRUITING

Study Officials

• Juan José Lahuerta

  Hospital 12 de Octubre

  STUDY CHAIR

• Joan Bladé

  Hospital Clinic of Barcelona

  STUDY CHAIR

Central Study Contacts

María-Victoria Mateos

CONTACT

+34 923 291 100; mvmateos@usal.es

Jesús San Miguel

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II Open-Label, Single Arm, Multicenter Study in which all patients with receive Dara-VRD and cilta-cel therapy

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: August 27, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): September 30, 2032
• Study Completion (Estimated): September 30, 2032
• Last Updated: October 26, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)