Trial Title:
Minimal Residual Disease-based Strategy With T-Cell Redirector After Treatment With Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (D-VRd) in Newly Diagnosed Multiple Myeloma
NCT ID:
NCT06353022
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasm, Residual
Dexamethasone
Lenalidomide
Bortezomib
Daratumumab
Conditions: Keywords:
Multiple Myeloma
Newly Diagnosed
Teclistamab
Talquetamab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Teclistamab
Description:
Maintenance therapy wtih teclistamab (administered via SC injections) for finite
duration. Teclistamab will be used in 28 day cycles following initial step up doses
Arm group label:
Talquetamab andTeclistamab
Arm group label:
Teclistamab and Lenalidomide
Other name:
No more information
Intervention type:
Drug
Intervention name:
Talquetamab
Description:
Maintenance therapy with talquetamab (administered via SC injections) for finite
duration. Talquetamab will be used in 28 day cycles following initial step up doses
Arm group label:
Talquetamab andTeclistamab
Other name:
No more information
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
Induction therapy with lenalidomide:
Lenalidomide 25 mg/day oral from Day 1 to Day 21.
Maintenance therapy lenalidomide (administered orally) for finite duration.
Arm group label:
Talquetamab andTeclistamab
Arm group label:
Teclistamab and Lenalidomide
Other name:
No more information
Intervention type:
Drug
Intervention name:
Bortezomib
Description:
Induction therapy with Borthezomib Cycle 1 to 6: Bortezomib 1.3 mg/m² SC twice a week on
Days 1, 4, 8 and 11
Arm group label:
Talquetamab andTeclistamab
Arm group label:
Teclistamab and Lenalidomide
Other name:
No more information
Intervention type:
Drug
Intervention name:
Daratumumab
Description:
Induction therapy with Daratumumab Cycle 1 to 6 Daratumumab 1800 mg SC on Days 1, 8, 15,
22 of Cycle 1 and Cycle 2 and on Days 1 and 15 of Cycle 3
Arm group label:
Talquetamab andTeclistamab
Arm group label:
Teclistamab and Lenalidomide
Other name:
No more information
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Induction therapy with Dexamethasone:
cycle 1 to 3 Dexamethasone 40 mg/day oral or IV on Days 1, 8, 15, 22 Cycle 4 to 6 -->
Dexamethasone 40 mg/day oral or IV on Days 1, 8, 15, 22
Arm group label:
Talquetamab andTeclistamab
Arm group label:
Teclistamab and Lenalidomide
Other name:
No more information
Summary:
This is a Phase 2 study, open-label, 2-cohort, multicenter, national, interventional in
patients with newly diagnosed multiple myeloma. The study will investigate teclistamab
(Tec) in combination with lenalidomide (Len) (Tec-Len; Cohort A) or in combination with
talquetamab (Tal) (Tec-Tal; Cohort B), allocated based on minimal residual disease (MRD)
status (MRD [-] [standard-risk] vs MRD [+] [high-risk] respectively).
The patient population will consist of adults men and women at least 18 years to younger
than 66 years of age, who meet eligibility criteria.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Each potential patient must satisfy all of the following criteria to be enrolled in the
study:
Age, Type of Patient, Disease Characteristics
1. Male or female patients must be at least 18 years of age at the time of consent
younger than 66 years.
2. Documented multiple myeloma satisfying the calcium elevation, renal insufficiency,
anemia, and bone lesions (CRAB) criteria and measurable disease (Source: Rajkumar
2014)
3. Newly diagnosed patients eligible for high dose therapy and autologous Stem cell
therapy.
4. Have a Karnofsky performance status score ≥50% (Eastern Cooperative Oncology Group
ECOG performance status ECOG score ≤2.
5. Have clinical laboratory values meeting the following criteria.
Sex and Contraceptive/Barrier Requirements
6. A female patient of childbearing potential must have a negative serum pregnancy test
within 10 to 14 days prior to the start of study treatment and again either a serum
or urine pregnancy test within 24 hours of the start of study treatment and must
agree to further serum or urine pregnancy tests during the study and for a period of
6 months after the last dose of study treatments.
7. A female patient must be :
1. Not of childbearing potential, or
2. Of childbearing potential and 1) Practicing 2 reliable methods of contraception
simultaneously including one highly effective method of contraception and one
other effective method of contraception starting 4 weeks prior to dosing,
throughout the study including during dose interruptions and for period of 6
months after the last dose of study treatments. For patients who are of
childbearing potential.
8. A female patient must agree not to donate eggs or freeze for future use, for the
purposes of assisted reproduction during the study and for a period of 6 months
after the last dose of other study treatments. Female patients should consider
preservation of eggs prior to study treatment as anti-cancer treatments may impair
fertility.
9. A male patient must wear a condom (with spermicidal foam/gel/film/cream/suppository)
when engaging in any activity that allows for passage of ejaculate to another person
during the study and for a period of 6 months after the last dose of study
treatments. If the male patient's partner is a female of childbearing potential, she
must also be practicing a highly effective method of contraception.
10. A male patient must agree not to donate sperm for the purpose of reproduction during
the study and for a period of 6 months after receiving the last dose of study. Male
patients should consider preservation of sperm prior to study treatment as anti
cancer treatments may impair fertility.
Informed Consent
11. Voluntary written informed consent must be given before performance of any study
related procedure not part of normal medical care, with the understanding that the
patient may withdraw consent at any time without prejudice to future medical care.
12. Willing and able to adhere to the lifestyle restrictions specified in this protocol.
13. Affiliation with French social security system or beneficiary from such system.
Non inclusion Criteria:
Medical Conditions
1. Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the NCI
CTCAE Version 5.0.
2. Chronic Obstructive Pulmonary Disease (COPD) with a Forced Expiratory Volume 1
(FEV1) <50% of predicted normal. Note that FEV1 testing is required for patients
with known or suspected of having COPD or asthma and patients must be excluded if
FEV1 <50% of predicted normal.
3. Moderate or severe persistent asthma within the past 2 years, uncontrolled asthma of
any classification. Note that FEV1 testing is required for patients known or
suspected asthma and patients must be excluded if FEV1 <50% of predicted normal.
4. Central Nervous System (CNS) involvement or clinical signs of meningeal involvement
of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar
cytology are required.
5. Plasma cell leukemia, Waldenström's macroglobulinemia, polyneuropathy, organomegaly,
endocrinopathy, M-protein, and skin changes (POEMS) syndrome (polyneuropathy,
organomegaly, endocrinopathy, M-protein, and skin changes), or primary light chain
amyloidosis.
6. Any ongoing myelodysplastic syndrome or B cell malignancy (other than multiple
myeloma).
7. Any history of malignancy, other than multiple myeloma, which is considered at high
risk of recurrence requiring systemic therapy.
8. Active malignancies other than multiple myeloma. The only allowed exceptions are
malignancies treated within the last 24 months that are considered cured:
1. Non-muscle invasive bladder cancer.
2. 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 with a Gleason Score ≤7a, treated locally only
5. Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma
in situ, or history of localized breast cancer
6. Other malignancy that is considered cured with minimal risk of recurrence in
consultation with the Sponsor
9. Stroke, transient ischemic attack, or seizure within 6 months prior to signing
informed consent form.
10. Presence of the following cardiac conditions:
1. New York Heart Association stage III or IV congestive heart failure
2. Myocardial infarction or coronary artery bypass graft ≤6 months prior to
enrollment
3. History of clinically significant ventricular arrhythmia or unexplained
syncope, not believed to be vasovagal in nature or due to dehydration
4. Uncontrolled cardiac arrhythmia or clinically significant ECG
(Electrocardiogram) abnormalities
5. History of severe non-ischemic cardiomyopathy
11. 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. Acute diffuse infiltrative pulmonary disease
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. Disabling psychiatric conditions, severe dementia, or altered mental status.
5. Any other issue that would impair the ability of the patient 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 patient or
that could prevent, limit, or confound the protocol- specified assessments.
6. History of noncompliance with recommended medical treatments
12. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to
any study drug (daratumumab, bortezomib, lenalidomide, dexamethasone, teclistamab or
talquetamab) or its excipients or analogues and study-required co-medication.
13. Incidence of gastrointestinal disease that may significantly alter the absorption of
oral drugs.
Prior/Concomitant Therapy
14. Prior or current systemic therapy or SCT for any plasma cell dyscrasia, with the
exception of emergency use of a short course of corticosteroids before treatment.
15. Received a strong CYP3A4 inducer within 5 half-lives prior to the first dose of
study treatment (Flockhart 2016: http://medicine.iupui.edu/flockhart/).
16. Plasmapheresis within 28 days prior to the first dose of study treatment.
17. Patient had major surgery or had significant traumatic injury 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 patient is expected
to be treated in the study or within 2 weeks after administration of the last dose
of study treatment.
18. Taken any disallowed therapies, Concomitant Therapy before the planned first dose of
study intervention.
19. Received a live, attenuated vaccine within 4 weeks before the first dose of study
drug. Non-live or replicating vaccines authorized for emergency use (eg, COVID-19)
are allowed.
Diagnostic Assessments
20. HIV infection (positive, history, treatment for HIV).
21. Hepatitis B infection (ie, HBsAg or HBV-DNA positive). In the event the infection
status is unclear, quantitative viral levels are necessary to determine the
infection status.
22. Active hepatitis C infection as measured by positive HCV-RNA testing. Patients with
a history of HCV antibody positivity must undergo HCV RNA testing. If a patient with
history of chronic hepatitis C infection (defined as both HCV antibody and HCV RNA
positive) completed antiviral therapy and has undetectable HCV-RNA 12 weeks
following the completion of therapy, the patient is eligible for the study.
Other non-inclusions
23. Patients unable to complete baseline next generation sequencing (NGS) evaluation at
Screening.
24. Patient is pregnant, a nursing mother, or planning to become pregnant while enrolled
in this study or within 6 months after the last dose of study treatment.
25. Patient plans to father a child while enrolled in this study or within 6 months
after the last dose of study treatment, whichever is later.
26. Any condition for which, in the opinion of the investigator, participation would not
be in the best interest of the patient or that could prevent, limit, or confound the
protocol-specified assessments.
27. Person under guardianship, trusteeship or deprived of freedom by a judicial or
administrative decision.
Gender:
All
Gender based:
Yes
Minimum age:
18 Years
Maximum age:
65 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
CH de la Côte Basque
Address:
City:
Bayonne
Zip:
64109
Country:
France
Facility:
Name:
CHU Caen
Address:
City:
Caen
Zip:
14033
Country:
France
Facility:
Name:
CHRU DIjon
Address:
City:
Dijon
Zip:
21000
Country:
France
Facility:
Name:
Chd Vendee
Address:
City:
La Roche-sur-Yon
Zip:
85925
Country:
France
Facility:
Name:
CHRU LILLE - Hôpital Claude Huriez
Address:
City:
Lille
Zip:
59037
Country:
France
Facility:
Name:
CHU Limoges
Address:
City:
Limoges
Zip:
87000
Country:
France
Facility:
Name:
CH Lyon Sud
Address:
City:
Lyon
Zip:
69495
Country:
France
Facility:
Name:
IPC Marseille Institut Paoli Calmettes
Address:
City:
Marseille
Zip:
13009
Country:
France
Facility:
Name:
CHU Montpellier
Address:
City:
Montpellier
Zip:
34295
Country:
France
Facility:
Name:
CHU de Nantes
Address:
City:
Nantes
Zip:
44093
Country:
France
Facility:
Name:
APHP Hôpital Saint Louis
Address:
City:
Paris
Zip:
75010
Country:
France
Facility:
Name:
APHP Hôpital Saint-Antoine
Address:
City:
Paris
Zip:
75012
Country:
France
Facility:
Name:
APHP Hôpital La Pitié Salpétrière
Address:
City:
Paris
Zip:
75013
Country:
France
Facility:
Name:
CHU BORDEAUX - Hôpital du Haut Lévêque
Address:
City:
Pessac
Zip:
33604
Country:
France
Facility:
Name:
CHU Poitiers
Address:
City:
Poitiers
Zip:
86000
Country:
France
Facility:
Name:
CHRU Rennes - Hôpital de Pontchaillou
Address:
City:
Rennes
Zip:
35033
Country:
France
Facility:
Name:
ICANS Institut de Cancérologie Strasbourg Europe
Address:
City:
Strasbourg
Zip:
67200
Country:
France
Facility:
Name:
CHU Toulouse
Address:
City:
Toulouse
Zip:
31059
Country:
France
Facility:
Name:
CHU Tours Hôpital Bretonneau
Address:
City:
Tours
Zip:
37044
Country:
France
Facility:
Name:
CHRU Nancy - Hôpitaux de Brabois
Address:
City:
Vandœuvre-lès-Nancy
Zip:
54511
Country:
France
Start date:
April 20, 2024
Completion date:
June 20, 2030
Lead sponsor:
Agency:
Nantes University Hospital
Agency class:
Other
Collaborator:
Agency:
Janssen Pharmaceutica
Agency class:
Industry
Source:
Nantes University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06353022
