This study has been transitioned to CTIS with ID 2023-503467-41-00 check the CTIS register for the current data. The purpose of the study is to compare the efficacy of talquetamab subcutaneous(ly) (SC) in combination with daratumumab SC and…
ID
Source
Brief title
Condition
- Haematopoietic neoplasms (excl leukaemias and lymphomas)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression-Free Survival (PFS)
PFS is defined as time from the date of randomization to the first
documentation of disease progression, or death due to any cause, whichever is
reported first.
Secondary outcome
Overall Response (Partial Response [PR] or Better)
Overall response (PR or better) is defined as percentage of participants who
have a PR or better per International Myeloma Working Group (IMWG) criteria.
Very Good Partial Response (VGPR) or Better Rate
VGPR or better rate is defined as the percentage of participants who achieve a
VGPR or better according to IMWG response criteria.
Complete Response (CR) or Better Rate
CR or better rate is defined as the percentage of participants who achieve CR
or better according to IMWG response criteria.
Overall Minimal Residual Disease (MRD) Negative CR
MRD-negative CR is defined as proportion of participants with CR or stringent
CR who achieve MRD negativity at a threshold of 10^-5 at any timepoint after
the first dose of study drug and before disease progression or start of
subsequent antimyeloma therapy.
Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of the
participant's death.
Progression-free Survival on Next-line Therapy (PFS2)
PFS2 is defined as the time interval between the date of randomization and date
of event, which is defined as progressive disease as assessed by investigator
on the first subsequent line of antimyeloma therapy, or death from any cause,
whichever occurs first.
Time to Next Therapy (TTNT)
TTNT is defined as the time from randomization to the start of subsequent
antimyeloma treatment.
Number of Participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant participating in a
clinical study that does not necessarily have a causal relationship with the
pharmaceutical/biological agent under study.
Number of Participants with AEs by Severity
Severity will be graded according to the National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI-CTCAE).
Serum Concentrations of Talquetamab
Serum concentrations of talquetamab will be reported.
Serum Concentrations of Daratumumab
Serum concentrations of daratumumab will be reported.
Number of Participants with Presence of Anti-Drug Antibodies (ADAs) to
Talquetamab
Number of participants with presence ADAs to talquetamab will be reported.
Number of Participants With Presence of Anti-Drug Antibodies (ADAs) to
Daratumumab
Number of participants with presence of ADAs to daratumumab will be reported.
Time to Worsening in Symptoms, Functioning, and Overall Health-Related Quality
of Life (HRQoL) as Assessed by Multiple Myeloma Symptom and Impact
Questionnaire (MySIm-Q)
The MySIm-Q is a disease-specific PRO assessment complementary to the European
Organization for Research and Treatment of Cancer Quality of Life Questionnaire
Core-30 item (EORTC-QLQ-C30).
Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by PROMIS
Short Form Version 2.0 -Physical Functioning 8c
The Patient-reported Outcomes Measurement Information System (PROMIS) Short
Form Version 2.0 -Physical Function 8c is an 8-item fixed--length short form
derived from the PROMIS Physical Function item bank.
Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by
EORTC-QLQ-C30
Time to worsening in symptoms, functioning, and HRQoL as assessed by
EORTC-QLQ-C30 will be reported.
Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by PRO-CTCAE
The National Cancer Institute's (NCI) PRO-CTCAE is an item library of common
AEs experienced by people with cancer that are appropriate for self-reporting
of treatment tolerability.
Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by EuroQol
Five Dimension Questionnaire 5-Level (EQ-5D-5L)
The EQ-5D-5L is a generic measure of health status. For purposes of this study,
the EQ-5D-5L will be used to generate utility scores for use in
cost-effectiveness analyses.
Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by Patient
Global Impression - Severity (PGI-S)
The PGI-S will be used as an anchor, external criterion, to determine
meaningful change in scores for the MySIm-Q and PROMIS SF PF 8c in this
population.
Change From Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by
Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q)
The MySIm-Q is a disease-specific PRO assessment complementary to the
EORTC-QLQ-C30.
Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by PROMIS
Short Form Version 2.0 -Physical Functioning 8c
The Patient-reported Outcomes Measurement Information System (PROMIS) Short
Form Version 2.0 -Physical Function 8c is an 8-item fixed-length short form
derived from the PROMIS Physical Function item bank.
Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by
EORTC-QLQ-C30
Time to worsening in symptoms, functioning, and HRQoL as assessed by
EORTC-QLQ-C30 will be reported.
Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by
PRO-CTCAE
The National Cancer Institute's (NCI) PRO-CTCAE is an item library of common
AEs experienced by people with cancer that are appropriate for self-reporting
of treatment tolerability.
Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by EuroQol
Five Dimension Questionnaire 5-Level (EQ-5D-5L)
The EQ-5D-5L is a generic measure of health status. For purposes of this study,
the EQ-5D-5L will be used to generate utility scores for use in
cost-effectiveness analyses.
Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by Patient
Global Impression - Severity (PGI-S)
The PGI-S will be used as an anchor, external criterion, to determine
meaningful change in scores for the MySIm-Q and PROMIS SF PF 8c in this
population.
Background summary
Multiple myeloma is a malignant plasma cell disorder that accounts for
approximately 10 percent (%) of all hematologic cancers, making it the second
most common hematologic malignancy. Overall rationale of study is that
combination treatments of talquetamab, daratumumab, pomalidomide and
dexamethasone may lead to enhanced clinical responses in treatment of relapsed
or refractory multiple myeloma through multiple mechanisms of action.
Study objective
This study has been transitioned to CTIS with ID 2023-503467-41-00 check the CTIS register for the current data.
The purpose of the study is to compare the efficacy of talquetamab
subcutaneous(ly) (SC) in combination with daratumumab SC and pomalidomide
(Tal-DP) and talquetamab SC in combination with daratumumab SC (Tal-D),
respectively, with daratumumab in combination with pomalidomide and
dexamethasone (DPd).
Study design
The study is divided into 3 phases: screening, treatment (until confirmed
progressive disease, death, intolerable toxicity, withdrawal of consent, or end
of the study, whichever occurs first), and posttreatment follow-up (until
death, withdrawal of consent, loss to follow-up, or end of the study, whichever
occurs first). Efficacy, safety (physical examinations, neurologic
examinations, Eastern Cooperative Oncology Group [ECOG] performance status,
clinical laboratory tests, vital signs, and AE monitoring), pharmacokinetics
(PK), immunogenicity, and biomarkers will be assessed at specified time points.
Total duration of study will be up to 6 years 6 months.
Intervention
Arm A: Talquetamab Subcutaneous (SC) in Combination With Daratumumab SC and
Pomalidomide (Tal-DP) - Participants will receive talquetamab and daratumumab
as SC injections; pomalidomide will be self-administered as a single dose
orally; dexamethasone may be given orally or intravenously as a pre-treatment
medication and study drug.
Arm B: Daratumumab in Combination With Pomalidomide and Dexamethasone (DPd) -
Participants will receive daratumumab as SC injection; pomalidomide will be
self-administered as a single dose orally; dexamethasone may be given orally or
intravenously as a pre-treatment medication and study drug.
Arm C: Talquetamab SC in Combination With Daratumumab SC (Tal-D) - Participants
will receive talquetamab and daratumumab as injection SC injection;
dexamethasone may be given orally or intravenously as a pre-treatment
medication and study drug.
Study burden and risks
The following adverse reactions have been observed with administration of
talquetamab to patients at various doses, either alone or in combination with
other drugs:
Occur very frequently: Cytokine inflammatory response, Fever, Skin problems,
Skin rash, Nail problems, Dysgeusia (altered taste), Dry mouth, Dysphagia
(difficulty swallowing) , Weight loss, Upper respiratory tract infection, Viral
infections & Neutropenia (low white blood cell count).
Occur frequently: Palmar-plantar erythrodysesthesia syndrome (hand-foot
syndrome), Stomatitis (sore mouth), Pneumonia, Febrile neutropenia (low white
blood cell count with fever) , Immuno-effector cell-associated neurotoxicity
syndrome (ICANS) , Encephalopathy (abnormal brain function).
Collection of blood: the subject may experience bruising or irritation at the
site where the needle enters the skin. Some patients may faint and, in rare
cases, get an infection.
Ecg (electrocardiogram): There is usually no risk associated with undergoing an
ecg. The stickers may pull on the subject's skin or cause redness or itching.
Bone marrow aspirate: During and after the procedure, the subject may
experience pain and discomfort. There is also a risk of infection and bleeding
at that site. The subject may also have an allergic reaction to the anesthetic.
MRI scan: There are no known risks or side effects of an MRI scan. If a
contrast agent is used, the investigator will inform the subject of possible
side effects or an allergic reaction.
CT scan: CT scans emit some radiation, so there is a small risk of causing
cancer and other conditions. Each individual scan carries a small risk.
Spirometry test: There are generally few complications that can occur during or
after a spirometry test. Immediately after the test is done, the subject may
feel a little dizzy or short of breath.
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Listed location countries
Age
Inclusion criteria
- >=18 years of age.
- Documented multiple myeloma as defined: a) Multiple myeloma diagnosis
according to the International Myeloma Working Group (IMWG) diagnostic criteria
and b) Measurable disease at screening as defined by any of the following: i)
Serum M-protein level greater than or equal to (>=) 0.5 grams per deciliter
(g/dL) (central laboratory); ii) Urine M-protein level >= 200 milligram (mg)/24
hours (central laboratory); iii) Light chain multiple myeloma without
measurable M-protein in the serum or the urine: serum immunoglobulin free light
chain >= 10 milligram per deciliter (mg/dL) (central laboratory), and abnormal
serum immunoglobulin kappa lambda free light chain ratio
- Relapsed or refractory disease as defined by: i) Relapsed disease is defined
as an initial response to prior treatment, followed by confirmed progressive
disease by IMWG criteria greater than (>) 60 days after cessation of treatment;
ii) Refractory disease is defined as less than (<) 25 percent (%) reduction in
monoclonal paraprotein (M-protein) or confirmed progressive disease by IMWG
criteria during previous treatment or less than or equal to (<=) 60 days after
cessation of treatment.
- Received at least 1 prior line of antimyeloma therapy including a proteasome
inhibitor (PI) and lenalidomide. Participants who have received only 1 prior
line of antimyeloma therapy must be considered lenalidomide-refractory (that
is, have demonstrated progressive disease by IMWG criteria on or within 60 days
of completion of lenalidomide-containing regimen). Participants who have
received >=2 prior lines of antimyeloma therapy must be considered lenalidomide
exposed
- Documented evidence of progressive disease based on investigator*s
determination of response by the IMWG criteria on or after their last regimen
- Have an Eastern Cooperative Oncology Group (ECOG) performance status score of
0, 1, or 2 at screening and immediately prior to the start of administration of
study treatment
Exclusion criteria
- Contraindications or life-threatening allergies, hypersensitivity, or
intolerance to study drug excipients
- Disease is considered refractory to an anti-cluster of differentiation 38
(CD38) monoclonal antibody as defined per IMWG consensus guidelines
(progression during treatment or within 60 days of completing therapy with an
anti-CD38 monoclonal antibody)
- Received prior pomalidomide therapy
- A maximum cumulative dose of corticosteroids to >=140 milligrams (mg) of
prednisone or equivalent within 14-day period before the first dose of study
drug
- Known active central nervous system (CNS) involvement or exhibits clinical
signs of meningeal involvement of multiple myeloma. If either is suspected,
negative whole brain magnetic resonance imaging (MRI) and lumbar cytology are
required
- Plasma cell leukemia (per IMWG criteria) at the time of screening,
Waldenström's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy,
M-protein, and skin changes (POEMS syndrome), or primary amyloid light chain
amyloidosis
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-503467-41-00 |
| EudraCT | EUCTR2021-000202-22-NL |
| CCMO | NL81800.056.22 |