The purpose of this study is to evaluate if the addition of daratumumab to Bortezomib, Thalidomide and Dexamethasone will increase the stringent complete response rate after consolidation therapy and increase the progression free survival after…
ID
Source
Brief title
Condition
- Haematopoietic neoplasms (excl leukaemias and lymphomas)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. The percentage of participants who achieve a stringent complete response
(sCR) after consolidation therapy
2. The percentage of increase in progression free survival after maintenance
therapy
Secondary outcome
1. PFS (from first randomization)
2.Time to progression (TTP)
3.Post-ASCT/ consolidation CR rate
4.Post-ASCT/consolidation MRD negative rate
5.Post-induction sCR rate
6.PFS2 (from first randomization)
7.OS (from first randomization)
Background summary
Induction prior to and consolidation and maintenance following ACST is now
emerging as a widely accepted treatment approach in newly diagnosed multiple
myeloma patients who are deemed to be eligible for high dose therapy with
autologous stem cell transplant.
The clinical utility of improving the depth of response using consolidation
therapy and preserving response in the long term using maintenance therapy has
been demonstrated in a number of studies. However, multiple myeloma still
remains incurable, and the agents currently available for long term therapy
have a number of shortcomings in terms of safety and tolerability.
Strategies directed at improving and maintaining response for longer periods of
time and new treatment options directed at alternative mechanisms are urgently
needed for patients with multiple myeloma.
Daratumumab with its novel mechanism of action together and good profile of
tolerability is ideally suited to being investigated as an adjunct to
induction, consolidation and subsequent long term maintenance therapy
.
The safety profile of daratumumab to date, which does not appear to overlap
with those known for approved agents, combined with its distinct MoA, suggest
that the therapeutic profile of daratumumab combined with various backbone
regimens may improve the treatment effect of these regimens. Additionally,
daratumumab as a single agent may prolong the progression free interval for
these patients. The detailed rationale for the study design elements are
provided in Section 3.2.
Study objective
The purpose of this study is to evaluate if the addition of daratumumab to
Bortezomib, Thalidomide and Dexamethasone will increase the stringent complete
response rate after consolidation therapy and increase the progression free
survival after daratumumab maintenance therapy in transplant eligible
participants with previously untreated Multiple Myeloma.
Study design
Part 1: Randomization between treatment with 4 Cycles of Bortezomib,
Thalidomide and Dexamethasone with or without daratumumab 16mg/kg induction
therapy, followed by Autologous Stem Cell Transplantation, followed by 2 cycles
of Bortezomib, Thalidomide and Dexamethasone wih or without daratumumab 16
mg/kg consolidation
Part 2 Second randomization between observation/ no further treatment or
daratumumab 16mg/kg every 8 weeks for 2 Years.
Follow up in arm A and arm B is limited to 2 years maximum duration.
Subjects who are not randomized in Part 2 will enter in the Follow-up Phase and
will be followed until disease progression, death or lost to follow up,
withdrawal of consent or study end, even if they receive subsequent anticancer
treatments.
Intervention
Patients are treated with 4 Cycles of Bortezomib, Thalidomide and Dexamethasone
with or without daratumumab 16mg/kg induction therapy, followed by Autologous
Stem Cell Transplantation, followed by 2 cycles of Bortezomib, Thalidomide and
Dexamethasone wih or without daratumumab 16 mg/kg consolidation
After that patients will have no further treatment/orbservation or daratumumab
16mg/kg every 8 weeks for 2 Years
Study burden and risks
The aim of this trial is, by adding daratumumab to VTD, to increase the
stringent complete response rate after consolidation therapy and increase the
progression free survival after daratumumab maintenance therapy for myeloma
patients
The primary safety profile of daratumumab is consistent with infusion-related
reactions. Based on the mode of action of daratumumab, a potential risk could
be infection, thrombocytopenia and anemia; therefore the protocol requires the
review of hematological laboratory results prior to daratumumab infusion.
Avenue Parmentier 75
Paris 75544
FR
Avenue Parmentier 75
Paris 75544
FR
Listed location countries
Age
Inclusion criteria
- diagnosis of previously untreated multiple myeloma (MM)
- have a confirmed diagnosis and eligible for high dose chemotherapy and
autologous stem cell transplantation, and an Eastern Cooperative Oncology Group
(ECOG) performance status score of 0, 1 or 2
Exclusion criteria
- previous treatment for Multiple Myeloma
- Primary amyloidosis, Plasma Cell Leukemia or Smoldering Multiple Myeloma
- Prior or concurrent exposure to systemic therapy or SCT for any plasma cell
dyscrasia, with the exception of an emergency use of a short course (equivalent
of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before
treatment, or received an investigational drug or used an invasive
investigational medical device within 4 weeks before Cycle 1, Day 1
- history of malignancy (other than Multiple Myeloma) within 10 years before
the date of randomization, except for the following if treated and not active:
basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical
carcinoma in situ, ductal carcinoma in situ of breast, or International
Federation of Gynecology and Obstetrics (FIGO) Stage 1 carcinoma of the cervix
- known chronic obstructive pulmonary disease (COPD) or moderate to severe
asthma
- any concurrent medical or psychiatric condition or disease (eg, autoimmune
disease, active systemic disease, myelodysplasia) that is likely to interfere
with the study procedures or results, or that in the opinion of the
investigator, would constitute a hazard for participating in this study
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 |
|---|---|
| EudraCT | EUCTR2014-004781-15-NL |
| CCMO | NL51783.078.15 |