Trial Title:
Bispecific T-cell Redirectors as Part of First Line Treatment in Transplant Eligible Multiple Myeloma Patients
NCT ID:
NCT06505369
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Dexamethasone
Lenalidomide
Bortezomib
Daratumumab
Conditions: Keywords:
Multiple Myeloma
Transplant Eligible
Talquetamab
Teclistamab
MRD negativity
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 with Dara -VRd + Consolidation with Talquetamab and Teclistamab as monotherapy in sequence
Other name:
JNJ-54767414
Intervention type:
Drug
Intervention name:
Bortezomib
Description:
Bortezomib will be administered by SC injection
Arm group label:
Induction with Dara -VRd + Consolidation with Talquetamab and Teclistamab as monotherapy in sequence
Other name:
EU Substance number SUB20020
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
Lenalidomide will be administered by oral route
Arm group label:
Induction with Dara -VRd + Consolidation with Talquetamab and Teclistamab as monotherapy in sequence
Other name:
EU Substance number SUB25389
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Dexamethasone will be administered by oral route
Arm group label:
Induction with Dara -VRd + Consolidation with Talquetamab and Teclistamab as monotherapy in sequence
Other name:
EU Substance number SUB07017MIG
Intervention type:
Drug
Intervention name:
Talquetamab
Description:
Talquetamab will be administered by SC injection
Arm group label:
Induction with Dara -VRd + Consolidation with Talquetamab and Teclistamab as monotherapy in sequence
Other name:
JNJ-64407564
Intervention type:
Drug
Intervention name:
Teclistamab
Description:
Teclistamab will be administered by SC injection
Arm group label:
Induction with Dara -VRd + Consolidation with Talquetamab and Teclistamab as monotherapy in sequence
Other name:
JNJ-64007957
Summary:
This is Phase 2, open-label, multicentre, non-randomised study evaluating participants
with newly diagnosed MM eligible for high-dose therapy. The goal of the study is to
determine if consolidation with T-cell redirectors - Talquetamab and Teclistamab in
sequence will improve the response depth: increase MRD negative CR rate.
Detailed description:
A total of 50 transplant-eligible patients with newly diagnosed multiple myeloma in need
of treatment will be enrolled.
The study consists of three phases: Induction, Consolidation, and Follow-up. Induction
will consist of Dara-VRd and consolidation Part I will include talquetamab and Part II
will include teclistamab.
Follow-up Phase After consolidation, treatment continues upon physician's choice: the
options are ASCT with maintenance or only maintenance with lenalidomide.
Efficacy will be evaluated by serum/urine electrophoresis monthly; by serum/urine
immunofixation, bone marrow morphology and flow cytometry when CR/sCR is suspected;
MRD will be evaluated by NGS ( at the level of 10-6) and FDG PET-CT ( by Deauville score)
at various timepoints during induction, consolidation and follow-up.
Participants quality of life, symptoms, functional and general well-being will be
captured using 3 PRO measures ( PRO-CTCAE, EORTC QLQ-C30, FACT-Cog).
The safety of study drugs will be assessed by physical examinations, vital signs, ECGs,
clinical laboratory tests, neurologic examinations (including ICE scores), ECOG
performance status, and AE monitoring according to NCI-CTCAE Version 5.0), grading of CRS
and ICANS will be assessed based on ASTCT guidelines.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participant must have documented MM satisfying the IMWG criteria.
2. Newly diagnosed patients eligible for high dose therapy and ASCT.
3. ECOG performance status score ≤2.
4. HIV-positive participants are eligible if they meet all of the following
1. No detectable viral load (ie, <50 copies/mL) at screening
2. CD4+ count >300 cells/mm3 at screening
3. No AIDS-defining opportunistic infection within 6 months of screening
4. Receiving HAART. Any changes in HAART due to resistance/progression should
occur at least 3 months prior to screening. A change in HAART due to toxicity
is allowed up to 4 weeks prior to screening.
5. Must sign an ICF indicating that the participant understands the purpose of, and
procedures required for, the study and is willing to participate in the study.
6. Willing and able to adhere to the lifestyle restrictions specified in this protocol.
7. A female participant of childbearing potential must have a negative highly sensitive
serum (β hCG) pregnancy test at screening
8. A female participant must be
1. Not of childbearing potential or
2. Of childbearing potential and practicing true abstinence; or have a sole
partner who is vasectomized; or practicing 2 effective methods of contraception
9. A female participant must agree not to donate eggs or freeze for future use during
the study and for 6 months after receiving the last dose of study treatment.
10. A male participant must wear a condom when engaging any sexual activity that allows
for passage of ejaculate to another person during the study and for a minimum of 100
days after receiving the last dose of study treatment.
11. A male participant must agree not to donate sperm for the purpose of reproduction
during the study and for a minimum of 100 days after receiving the last dose of
study treatment.
12. Have clinical laboratory values meeting the following criteria
1. Hemoglobin ≥8 g/dL
2. Platelets ≥75×109/L
3. ANC ≥1.0×109/L
4. AST and ALT ≤2.5×ULN
5. eGFR ≥30 mL/min
6. Total bilirubin <1.5×ULN
Exclusion Criteria:
1. Waldenström's macroglobulinemia, POEMS syndrome, or primary amyloid light chain
amyloidosis.
2. Known active CNS involvement or exhibits clinical signs of meningeal involvement of
MM. If either is suspected, negative whole brain MRI and lumbar cytology are
required.
3. Peripheral neuropathy or neuropathic pain Grade 2 or higher
4. Excluded for any of the following:
1. Any ongoing myelodysplastic syndrome or B cell malignancy (other than MM).
2. Any history of malignancy, other than MM, which is considered at high risk of
recurrence requiring systemic therapy.
3. Any active malignancy (ie, progressing or requiring treatment change in the
last 24 months) other than MM. The only allowed exceptions are malignancies
treated within the last 24 months that are considered cured:
1. Non-muscle invasive bladder cancer (solitary Ta-PUN-LMP or low grade, <3
cm, no CIS).
2. Non-melanoma skin cancers treated with curative therapy or localized
melanoma treated with curative surgical resection alone.
3. Non-invasive cervical cancer.
4. Breast cancer: adequately treated lobular carcinoma in situ or ductal
carcinoma in situ or history of localized breast cancer (anti-hormonal
therapy is permitted).
5. Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated
locally only (RP/RT/focal treatment).
6. Other malignancy that is considered cured with minimal risk of recurrence
in consultation with the sponsor's medical monitor.
5. Stroke within 6 months prior to signing ICF.
6. Presence of the following cardiac conditions:
1. New York Heart Association stage III or IV congestive heart failure (see
Appendix )
2. Myocardial infarction or coronary artery bypass graft ≤6 months prior to
enrollment, or an unstable or uncontrolled disease/condition related to or
affecting cardiac function (eg, unstable angina)
3. Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities
4. History of clinically significant ventricular arrhythmia or unexplained
syncope, not believed to be vasovagal in nature or due to dehydration
5. History of severe non-ischemic cardiomyopathy
7. Concurrent medical or psychiatric condition or disease that is likely to interfere
with study procedures or results, or that in the opinion of the investigator would
constitute a hazard for participating in this study, such as:
1. Uncontrolled diabetes
2. Evidence of active systemic viral, fungal, or bacterial infection, requiring
systemic antimicrobial therapy
3. History of autoimmune disease with the exception of vitiligo, type I diabetes,
and prior autoimmune thyroiditis that is currently euthyroid based on clinical
symptoms and laboratory testing
4. Gastrointestinal disease that may significantly alter the absorption of oral
drugs
5. Disabling psychiatric conditions (eg, alcohol or drug abuse), severe dementia,
or altered mental status
8. Any other issue that would impair the ability of the participant to receive or
tolerate the planned treatment at the investigational site, to understand informed
consent or 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
9. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to
any study drug or its excipients
10. Any of the following:
1. Hepatitis B infection (ie, HBsAg or HBV-DNA positive).
2. Active hepatitis C infection as measured by positive HCV-RNA testing.
11. Prior or current systemic therapy or stem cell transplantation for any plasma cell
dyscrasia, with the exception of emergency use of a short course (equivalent of
dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment.
12. Major surgery within 2 weeks prior to the start of administration of study
treatment, or will not have fully recovered from surgery, or has major surgery
planned during the time the participant is expected to be treated in the study or
within 2 weeks after administration of the last dose of study treatment.
13. Contraindications to the use of Dara-VRd per SmPC.
14. Prior or concurrent exposure to any of the following, in the specified time frame
prior to first dose of study treatment:
1. Investigational vaccine other than SARS-CoV-2 vaccine approved/in use under
emergency approval within 4 weeks. Non-live or non-replicating vaccines
authorized for emergency use (eg, COVID-19) by local health authorities are
allowed.
2. Live, attenuated vaccine within 4 weeks
3. Monoclonal antibody therapy within 21 days (not used for the treatment of MM)
4. Received a strong CYP3A4 inducer within 5 half-lives prior to start of
administration of study treatment
15. Participant is pregnant, breastfeeding, or planning to become pregnant while
enrolled in this study or within 6 months after the last dose of study treatment.
16. Participant plans to father a child while enrolled in this study or within 100 days
after the last dose of study treatment.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Copenhagen University Hospital (Rigshospitalet)
Address:
City:
Copenhagen
Zip:
2100
Country:
Denmark
Status:
Not yet recruiting
Contact:
Last name:
Agoston Gyula Szabo, MD; PhD
Phone:
+45-35-45-37-36
Email:
agoston.gyula.szabo@regionh.dk
Facility:
Name:
Odense University Hospital
Address:
City:
Odense
Zip:
5000
Country:
Denmark
Status:
Not yet recruiting
Contact:
Last name:
Thomas Lund, MD; PhD
Phone:
+45 2145 0256
Email:
Thomas.Lund2@rsyd.dk
Facility:
Name:
Vejle hospital
Address:
City:
Vejle
Zip:
7100
Country:
Denmark
Status:
Not yet recruiting
Contact:
Last name:
Sarah Leeth Hansen Farmer, MD; PhD
Phone:
+45 7940 5957
Email:
Sarah.Farmer1@rsyd.dk
Facility:
Name:
North Estonia Medical Centre
Address:
City:
Tallinn
Zip:
13419
Country:
Estonia
Status:
Recruiting
Contact:
Last name:
Diana Loigom, MD
Phone:
+372 617 2173
Email:
diana.loigom@regionaalhaigla.ee
Facility:
Name:
Oslo University Hospital, Oslo Myeloma Centre
Address:
City:
Oslo
Zip:
0450
Country:
Norway
Status:
Not yet recruiting
Contact:
Last name:
Jakob Nordberg Nørgaard, MD
Phone:
(+47) 23 07 04 60
Email:
jaknoe@ous-hf.no
Facility:
Name:
Stavanger University Hospital
Address:
City:
Stavanger
Zip:
4068
Country:
Norway
Status:
Not yet recruiting
Contact:
Last name:
Einar Haukås, MD; PhD
Contact backup:
Phone:
+47 51518383
Email:
einar.haukas@sus.no
Facility:
Name:
St. Olavs Hospital
Address:
City:
Trondheim
Zip:
7030
Country:
Norway
Status:
Not yet recruiting
Contact:
Last name:
Tobias Schmidt Slørdahl, MD; PhD
Contact backup:
Phone:
(+47) 911 45 009
Email:
tobias.s.slordahl@ntnu.no
Start date:
June 19, 2024
Completion date:
October 2028
Lead sponsor:
Agency:
North Estonia Medical Centre
Agency class:
Other
Collaborator:
Agency:
Janssen Pharmaceutica
Agency class:
Industry
Source:
North Estonia Medical Centre
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06505369
