* To establish the safety profile of daratumumab when given in combination with lenalidomide and dexamethasone in subjects with relapsed or relapsed and refractory MM
ID
Source
Brief title
Condition
- Plasma cell neoplasms
- Plasma cell neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main variable for this study, the incidence of side effects.
Secondary outcome
Secondary end points are:
- The rate of response
- Pharmacokinetic parameters
- The time to progression
- Duration of response
- Survival
Background summary
Multiple myeloma (MM) is a plasma cell disorder, characterized by uncontrolled,
malignant proliferation and accumulation of plasma cells. In the majority of
patients, the malignant plasma cells produce a monoclonal protein (M protein or
paraprotein).
Multiple myeloma accounts for approximately 1% of all malignancies and 10% of
all hematologic malignancies, with a higher frequency in African Americans
where it accounts for 20% of all hematologic malignancies. At present, there is
no cure available.
Treatments include combination chemotherapy, proteasome inhibition,
immunomodulatory drugs, high-dose chemotherapy, and autologous stem cell
transplantation (auto SCT).
Study objective
* To establish the safety profile of daratumumab when given in combination with
lenalidomide and dexamethasone in subjects with relapsed or relapsed and
refractory MM
Study design
In this Phase I/II safety trial of daratumumab in combination with lenalidomide
and low-dose dexamethasone (Len/Dex), a standard Phase 1 *3 + 3* design is
appropriate to adequately observe DLTs associated with the regimen while not
exposing an undue number of subjects to doses that may be subtherapeutic. The
dose escalation part of the trial (Part 1) will be followed by a cohort
expansion part (Part 2) in which subjects will be enrolled into 2 cohorts of 16
subjects each at the MTD (or maximum tested dose) determined during Part 1.
Part 2 of this trial will allow for a greater degree of experience with the
combination therapy at what is expected to be a therapeutic dose of daratumumab
and Len/Dex.
Intervention
Skeletal survey:
X-rays or CT scan of the entire body, including the skull, is required.
Additional studies (X-ray, CT scan or
MRI) can be performed, this is at the discretion of the investigator (eg to
confirm the response to new
symptoms or pain in the bones to be evaluated).
Blood and urine analysis will be performed to determine the following
values**: biochemistry, hematology, Hepatitis B and
Cytomegalovirus Serology, pregnancy, Serum immunoglobulin A, M and G
(M-component) Urinalysis for Mcomponent
Serum free light chain ratio and pharmacokinetic / pharmacodynamic study of
the concentration daratumumab
the serum.
bone marrow examination
Study burden and risks
Skeletal survey:
X-rays or CT scan of the entire body, including the skull, is required.
Additional studies (X-ray, CT scan or
MRI) can be performed, this is at the discretion of the investigator (eg to
confirm the response to new
symptoms or pain in the bones to be evaluated).
Blood and urine analysis will be performed to determine the following
values**: biochemistry, hematology, Hepatitis B and
Cytomegalovirus Serology, pregnancy, Serum immunoglobulin A, M and G
(M-component) Urinalysis for Mcomponent
Serum free light chain ratio and pharmacokinetic / pharmacodynamic study of
the concentration daratumumab
the serum.
bone marrow examination
Turnhoutseweg 30
Beerse 2340
NL
Turnhoutseweg 30
Beerse 2340
NL
Listed location countries
Age
Inclusion criteria
Before entering Phase 1 of the study, subjects must:
1. Have relapsed multiple myeloma after receiving a minimum of 2 and a maximum of 4 prior lines of therapy and be eligible for treatment with Len/Dex.
2. Have measurable levels of M component, defined as serum M component* 1.0 g/dL and/or urine M component * 200 mg/24 hour sample.
3. Be * 18 years of age.
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Attachment 1).
5. Have a life expectancy of * 3 months.
6. Provide signed informed consent after receipt of oral and written information about the study and before any study-related activity is performed.;Before entering Phase 2 of the study, subjects must:
1. - Have received at least 1 prior line of therapy for multiple myeloma (refer to Attachment 2).
- Have achieved a response (PR or better) to at least one prior regimen.
- Have documented evidence of progressive disease (PD) as defined by the IMWG criteria on or after their last regimen.
2. Have measurable levels of M component, defined as serum M component * 1.0 g/dL and/or urine M component * 200 mg/24 hour sample.
3. Be * 18 years of age.
4. Have an ECOG performance status score of 0, 1, or 2 (Attachment 1).
5. Have a life expectancy of * 3 months.
6. Provide signed informed consent after receipt of oral and written information about the study and before any study-related activity is performed.
Exclusion criteria
1. Have previously received an allogenic stem cell transplant.
2. Have received auto SCT within 12 weeks before the first infusion.
3. Have received antimyeloma treatment, radiotherapy, or any experimental drug or therapy within 2 weeks before the first infusion.
4.Have discontinued lenalidomide due to any treatment-related adverse
event or be refractory to any dose of lenalidomide.
Refractory to lenalidomide is defined as either:
- Subjects whose disease progresses within 60 days of lenalidomide, or
- Subjects whose disease is nonresponsive while on any dose of
lenalidomide. Nonresponsive disease is defined as either failure to
achieve at least an MR or development of PD while on lenalidomide.
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 | EUCTR2011-005709-62-NL |
| ClinicalTrials.gov | NCT01615029 |
| CCMO | NL39344.041.12 |