Trial Title:
Teclistamab-Daratumumab and Talquestamab-Daratumumab in Newly Diagnosed High-risk Multiple Myeloma
NCT ID:
NCT05849610
Condition:
High-Risk de Novo Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Lenalidomide
Bortezomib
Daratumumab
Conditions: Keywords:
High-Risk de novo Multiple Myeloma
Teclistamab
Talquetamab
Daratumumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Daratumumab
Description:
Daratumumab will be administered by SC injection.
Arm group label:
Induction VRD-Dara + Intensification Tec-Dara + Maintenance Tec-Dara + ERI Tal-Dara
Intervention type:
Drug
Intervention name:
Bortezomib
Description:
Bortezomib dose will be calculated using the patient's actual body surface area (BSA) at
baseline and will be administered by subcutaneous (SC) injection.
Arm group label:
Induction VRD-Dara + Intensification Tec-Dara + Maintenance Tec-Dara + ERI Tal-Dara
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
Lenalidomide will be administered by oral route.
Arm group label:
Induction VRD-Dara + Intensification Tec-Dara + Maintenance Tec-Dara + ERI Tal-Dara
Intervention type:
Drug
Intervention name:
Teclistamab
Description:
Teclistamab will be administered by SC injection.
Arm group label:
Induction VRD-Dara + Intensification Tec-Dara + Maintenance Tec-Dara + ERI Tal-Dara
Other name:
JNJ-64007957
Intervention type:
Drug
Intervention name:
Talquetamab
Description:
Talquetamab will be administered by subcutaneous (SC) injection.
Arm group label:
Induction VRD-Dara + Intensification Tec-Dara + Maintenance Tec-Dara + ERI Tal-Dara
Other name:
JNJ-64407564
Summary:
The goal of this Phase 2, open-label, multicenter, non-randomized pilot study is to
evaluate the efficacy (in terms of MRD negative CR rate after Intensification therapy)
and safety of Tec-Dara (Teclistamab+Daratumumab) and Tal-Dara (Talquetamab+Daratumumab)
in de novo high-risk multiple myeloma (DNHRMM) patients.
Detailed description:
A total of 30 transplant eligible or elderly fit patients with high risk multiple myeloma
will be enrolled
1. Patients will receive a 4-cycle Dara+VRD (daratumumab, bortezomib, lenalidomide,
dexamethasone) INDUCTION therapy. Cycles will be of 28 days (4-week cycles) in
duration for daratumumab and for VRD.
After the 4-cycle Induction, all patients will receive the 1st INTENSIFICATION treatment
which consists of 6 cycles of Tec-Dara. Cycles will be of 28 days (4-week cycles) in
duration for daratumumab and for teclistamab.
1st Intsensification, patients will receive a 6-cycle Dara+Teclistamab.
2. At the end of 1st Intensification timepoint treatments depends on MRD status:
2.1) MRD negative patients in CR at the end of Intensification will receive MAINTENANCE
therapy with Tec-Dara continuously for 2 years. Cycles will be of 28-days in duration for
Tec-Dara. Teclistamab (SC) and daratumumab (SC).
2.2) MRD positive patients or patients who didn't achieve CR despite MRD negativity, will
have EARLY RESCUE INTERVENTION (ERI) with Tal-Dara for 6 cycles. MRD and response will be
evaluated again after 6 cycles treatment with Tal-Dara. MRD negative patients in CR will
receive continuous treatment with Tal-Dara for 2 years.
2.2.1 Early Rescue Intervention with Tal-Dara: Patients who are MRD+ after
intensification or who convert from MRD negative into positive or experience a relapse
from CR (without fulfilling criteria for disease progression) at any time during Tec-Dara
treatment will have ERI with Tal-Dara. Cycles will be of 28 days in duration.
2.2.2. MRD negative patients in CR will receive continuous treatment with Tal-Dara for 2
years. Cycles will be of 28-days of duration for Tal-Dara.
4. SALVAGE therapy: If the patient remains MRD+ or doesn't achieve CR despite MRD
negativity after 6 cycles of ERI with Tal-Dara or has disease progression at any
time, further treatment will be offered as per the investigation decision outside of
the study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patient is, in the investigator's opinion, willing and able to comply with the
protocol requirements.
- Patient has given voluntary written informed consent before performance of any
study-related procedure nor part of normal medical care, with the understanding that
consent may be withdrawn by the patient at any time without prejudice to their
future medical care.
- Patient is ≥ 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.
- Patient has documented diagnosis of multiple myeloma according to IMWG diagnostic
criteria, with at least one of the following high-risk features:
1. High-risk FISH: del(17p), t(4;14), t(14;16) and 1q amplifications.
2. R-ISS 3
3. Presence of extramedullary disease, defined as presence of paramedullary
lesions or extramedullary plasmacytoma.
Note: In order to have a representative population with high-risk features, 50% of
patients included will have ultra-high risk disease defined as: i) R-ISS 3; ii) Double
hit (at least two high-risk cytogenetic abnormalities); iii) One high-risk cytogenetic
abnormality + extramedullary disease.
- Patients eligible for transplant with age ≤ 70 years old (young and
transplant-eligible) or patients not eligible for transplant with ECOG-PS modified
frailty score of 0-1 (elderly-fit).
- Patient has an ECOG performance status of 0, 1or 2.
Exclusion Criteria:
- Prior or current systemic therapy or SCT for any plasma cell dyscrasia, with the
exception of 1 cycle of antimyeloma treatment or the emergency use of a short course
(equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids
before treatment while waiting for results of genetic analysis. A cycle of therapy
may include treatment with proteasome inhibitors, immunomodulatory drugs, alkylators
and corticosteroids, and/or anti-CD38 monoclonal antibodies (i.e,
bortezomib-thalidomide-dexamethasone, D-VTD, bortezomib-lenalidomide-dexamethasone,
or bortezomib-cyclophosphamide-dexamethasone, are valid options).
- Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the
NCI-CTCAE Version 5.
- Patient has a diagnosis of primary light chain amyloidosis, monoclonal gammopathy of
undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell
leukemia or active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy,
M-protein, and skin changes) at the time of screening.
- Myelodysplastic syndrome or active malignancies (ie, progressing or requiring
treatment change in the last 24 months) other than relapsed/refractory multiple
myeloma. The only allowed exceptions are malignancies treated within the last 24
months that are considered completely cured:
1. Non-muscle invasive bladder cancer (solitary Ta-papillary urothelial neoplasm
of low malignancy or low grade, < 3 cm, no carcinoma in situ).
2. Skin cancer (non-melanoma skin cancers treated with curative therapy or
localized melanoma treated with curative surgical resection alone).
3. Noninvasive cervical cancer.
4. Localized prostate cancer (M0, N0) with a Gleason score of ≤ 7a, treated
locally only (radical prostatectomy/radiation therapy/focal treatment).
5. Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma
in situ, localized breast cancer and receiving antihormonal agents.
6. Other malignancy that is considered cured with minimal risk of recurrence.
- Patient has CNS or exhibits clinical signs of meningeal involvement of multiple
myeloma. If either is suspected, negative whole brain MRI and lumbar cytology are
required.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hospital Germans Trials i Pujol
Address:
City:
Badalona
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Albert Oriol, Dr
Email:
aoriol@iconcologia.net
Facility:
Name:
Hospital Clinic i Provincial de Barcelona
Address:
City:
Barcelona
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Laura Rosiñol, Dr
Phone:
93 2275400
Email:
LROSINOL@clinic.cat
Investigator:
Last name:
Laura Rosiñol
Email:
Principal Investigator
Facility:
Name:
Hospital Doce de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Joaquín Martínez-López, Dr
Facility:
Name:
Hospital Virgen de la Arrixaca
Address:
City:
Murcia
Country:
Spain
Status:
Recruiting
Contact:
Last name:
María José Moreno Belmonte, Dr
Phone:
+ 34 968 36 95 00
Facility:
Name:
Clinica Universidad de Navarra
Address:
City:
Pamplona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Paula Rodríguez
Investigator:
Last name:
Paula Rodríguez
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario de Salamanca
Address:
City:
Salamanca
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Maria Victoria Mateos Manteca
Investigator:
Last name:
Maria Victoria Mateos Manteca
Email:
Principal Investigator
Facility:
Name:
H. Universitario Marqués de Valdecilla
Address:
City:
Santander
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Enrique Ocio
Email:
Enriquem.ocio@scsalud.es
Investigator:
Last name:
Enrique Ocio
Email:
Principal Investigator
Facility:
Name:
Complejo Hospitalario Santiago (CHUS)
Address:
City:
Santiago De Compostela
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Marta Sonia González Pérez
Email:
marta.sonia.gonzalez.perez@sergas.es
Investigator:
Last name:
Marta Sonia González Pérez
Email:
Principal Investigator
Facility:
Name:
Hospital Vírgen del Rocío
Address:
City:
Sevilla
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Eusebio Martin Chacón
Investigator:
Last name:
Eusebio Martin Chacón
Email:
Principal Investigator
Facility:
Name:
Hospital Universitari i Politecnic la Fe
Address:
City:
Valencia
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
Mario Arnao Herraiz, Dr
Phone:
96 1244192
Email:
arnao_mar@gva.es
Investigator:
Last name:
Mario Arnao Herraiz
Email:
Principal Investigator
Start date:
November 2023
Completion date:
July 2029
Lead sponsor:
Agency:
PETHEMA Foundation
Agency class:
Other
Collaborator:
Agency:
Janssen Pharmaceutica
Agency class:
Industry
Source:
PETHEMA Foundation
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05849610
