Smoldering Multiple Myeloma
Conditions
Keywords
Smoldering Multiple Myeloma
Brief summary
The purpose of this study is to evaluate the anti-tumor activity, safety and pharmacology of two dose regimens (0.2 and 2 mg/kg)of IPH2101 in patients with Smoldering Multiple Myeloma.
Detailed description
This is a randomized Phase II, open label, multi-centre study, with two independent arms. Patients receive 6 injections of IPH2101, at the dose of 0.2 mg/kg or 2 mg/kg (according to their randomization) administered over one hour infusion at four weeks intervals. A patient whose disease achieves at least a minimal response to study treatment at any time during the initial period of 6 cycles can be treated with an additional period of treatment of 6 cycles. Patients are followed 6 months after treatment completion or until a KIR occupancy level \< 30% (i.e if the time required for KIR desaturation was \> 6 months), whichever is longer.
Interventions
DRUGIPH2101
0.2 mg/Kg or 2mg/Kg, every 4 weeks by intravenous route over 1 hour, for 6 or up to 12 cycles
Sponsors
Innate Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. SMM of any risk level according to a definition derived of the International Myeloma Working Group definition ( Br J Haematol 2003; 121: 749) : Serum M protein ≥ 3 g/dl , AND/OR Bone Marrow plasma cells ≥ 10 % with no evidence of end-organ damage (CRAB) * (C)Absence of hypercalcemia : Ca \< 10.5 mg/dl * (R)Absence of renal failure : creatinine \< 2mg/dl (177 μmol/l) or calculated creatinine clearance(according to MDRD) \> 50 ml/min * (A)Absence of anemia : Hb \> 11 g/dl * (B)Absence of lytic bone lesion on standard skeletal survey (MRI could be used if clinically indicated) 2. Measurable disease defined as a disease with a serum M protein ≥ 1 g/dl 3. No evidence of fatigue, recurrent infections or any clinical suspicion of MM 4. Diagnosis of SMM confirmed on two consecutive assessments (ie fluctuation under 25% of serum protein level) performed with at least a 4 week interval. 5. Age \> 18 years or \< 75 years 6. ECOG performance status of 0 or 1 7. Male or female patient who accepts and is able to use recognised effective contraception (oral contraceptives, IUCD, barrier method of contraception in conjunction with spermicidal jelly) throughout the study when relevant 8. Informed consent signed by the patient
Exclusion criteria
1. Previous treatment having a proven or potential impact on myelomatous cells proliferation or survival (including IMiDs or proteasome inhibitors, conventional chemotherapies within the last 5 years, steroids within the last month prior to enrolment). Previous bisphosphonates started less than 3 months prior to enrolment. 2. Use of any investigational agent within the last 3 months 3. Clinical laboratory values at screening * Platelet \< 75 x 10\^9 /l * ANC \< 1.5 x 10\^9 /l * Bilirubin levels \>1.5 ULN ; ALT and AST \> 3 ULN (grade 1 NCI) 4. Primary or associated amyloidosis 5. Abnormal cardiac status with any of the following 1. NYHA stage III or IV congestive heart failure 2. myocardial infarction within the previous 6 months 3. symptomatic cardiac arrhythmia requiring treatment or persisting despite appropriate treatment 6. Current active infectious disease or positive serology for HIV, HCV or positive Hbs Antigen 7. History of or current auto-immune disease 8. History of other active malignancy within the past five years (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma). 9. Serious concurrent uncontrolled medical disorder 10. History of allograft or solid organ transplantation 11. Pregnant or lactating women 12. Any condition potentially hampering compliance with the study protocol and follow-up schedule
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Patients Achieving an Objective Response | from start to end of study (14 months) | The primary end point is the rate of patients achieving an objective response (defined according to the International Myeloma Working Group uniform response criteria), including minimal response, (as derived from the European Society for Blood and Marrow Transplantation criteria), achieved at any time until end of study and confirmed on two consecutive assessments at 4 weeks interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Assessment | Adverse events collected from screening visit (date of signature of Inform Consent Form) up to the End of Study, up to 14 months | adverse events, physical examination and biological changes during the whole clinical trial. |
| Pharmacodynamics of IPH2101 | from start to end of study (14 months) | biological activity of IPH2101 on KIR occupancy at End of Treatment |
| Secondary Anti-tumor Activity | from start to end of study (14 months) | * any change of M-protein in serum occurring during the study (\>25 percentage increase in level of serum M-protein) * progression to active Multiple Myeloma Definition of active Multiple Myeloma: Evidence of progression based on the IMWG criteria for progressive disease in myeloma and any one or more of the following felt related to the underlying clonal plasma cell proliferative disorder : * Development of new soft tissue plasmacytomas or bone lesions * Hypercalcemia (\> 11mg/100ml) * Decrease in hemoglobin of \> 2g/100ml * Rise in serum creatinine by 2 mg/100ml or more |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNikhil Munshi, MD
Dana-Farber Cancer Institute- Medical Oncology- Boston MA-USA
Participant flow
Recruitment details
There were 44 patients screened, 14 subjects were not randomized, 12 of whom were screen failures, 30 patients randomized.
Pre-assignment details
All patients enrolled were screened in order to verify the inclusion/exclusion criteria. All patients enrolled (30 patients) were analyzed.
Participants by arm
| Arm | Count |
|---|---|
| IPH2101 0.2 mg/kg 0.2 mg/Kg every 4 weeks by intravenous route over 1 hour, for 6 or up to 12 cycles | 16 |
| IPH2101 2 mg/kg 2 mg/Kg every 4 weeks by intravenous route over 1 hour, for 6 or up to 12 cycles | 14 |
| Total | 30 |
Baseline characteristics
| Characteristic | IPH2101 2 mg/kg | IPH2101 0.2 mg/kg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 6 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 10 Participants | 21 Participants |
| Age, Continuous | 58.4 years STANDARD_DEVIATION 13.11 | 63.6 years STANDARD_DEVIATION 7.62 | 61.2 years STANDARD_DEVIATION 10.69 |
| Region of Enrollment United States | 14 participants | 16 participants | 30 participants |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 13 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| other Total, other adverse events | 12 / 16 | 12 / 14 |
| serious Total, serious adverse events | 2 / 16 | 0 / 14 |
Outcome results
Primary
Rate of Patients Achieving an Objective Response
The primary end point is the rate of patients achieving an objective response (defined according to the International Myeloma Working Group uniform response criteria), including minimal response, (as derived from the European Society for Blood and Marrow Transplantation criteria), achieved at any time until end of study and confirmed on two consecutive assessments at 4 weeks interval.
Time frame: from start to end of study (14 months)
Population: The ITT population included all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IPH2101 0.2 mg/kg | Rate of Patients Achieving an Objective Response | 0 participants |
| IPH2101 2 mg/kg | Rate of Patients Achieving an Objective Response | 0 participants |
Secondary
Pharmacodynamics of IPH2101
biological activity of IPH2101 on KIR occupancy at End of Treatment
Time frame: from start to end of study (14 months)
Population: all subjects who received at least 1 dose of IPH2101
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IPH2101 0.2 mg/kg | Pharmacodynamics of IPH2101 | 73.1 % of occupancy of killer like receptor |
| IPH2101 2 mg/kg | Pharmacodynamics of IPH2101 | 92 % of occupancy of killer like receptor |
Secondary
Safety Assessment
adverse events, physical examination and biological changes during the whole clinical trial.
Time frame: Adverse events collected from screening visit (date of signature of Inform Consent Form) up to the End of Study, up to 14 months
Population: The safety population included all subjects who received at least 1 dose of IPH2101
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IPH2101 0.2 mg/kg | Safety Assessment | 16 Patients with any AE |
| IPH2101 2 mg/kg | Safety Assessment | 14 Patients with any AE |
Secondary
Secondary Anti-tumor Activity
* any change of M-protein in serum occurring during the study (\>25 percentage increase in level of serum M-protein) * progression to active Multiple Myeloma Definition of active Multiple Myeloma: Evidence of progression based on the IMWG criteria for progressive disease in myeloma and any one or more of the following felt related to the underlying clonal plasma cell proliferative disorder : * Development of new soft tissue plasmacytomas or bone lesions * Hypercalcemia (\> 11mg/100ml) * Decrease in hemoglobin of \> 2g/100ml * Rise in serum creatinine by 2 mg/100ml or more
Time frame: from start to end of study (14 months)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IPH2101 0.2 mg/kg | Secondary Anti-tumor Activity | serum M-protein progression | 4 Participant |
| IPH2101 0.2 mg/kg | Secondary Anti-tumor Activity | Progression to active Multiple Myeloma | 2 Participant |
| IPH2101 2 mg/kg | Secondary Anti-tumor Activity | serum M-protein progression | 8 Participant |
| IPH2101 2 mg/kg | Secondary Anti-tumor Activity | Progression to active Multiple Myeloma | 3 Participant |