Open randomised phase II study evaluating the anti-tumour activity, safety and pharmacology of two different dose regimens of IPH 2101, a human monoclonal anti-KIR antibody, in patients with multiple myeloma in stable partial response after a first line therapy

• Register: EUCTR
• Last refreshed on: 4 April 2022
• Main ID: EUCTR2009-012136-33-FR
• Date of registration: 28/05/2009
• Prospective Registration: Yes
• Primary sponsor: Innate Pharma
• Public title: Open randomised phase II study evaluating the anti-tumour activity, safety and pharmacology of two different dose regimens of IPH 2101, a human monoclonal anti-KIR antibody, in patients with multiple myeloma in stable partial response after a first line therapy
• Scientific title: Open randomised phase II study evaluating the anti-tumour activity, safety and pharmacology of two different dose regimens of IPH 2101, a human monoclonal anti-KIR antibody, in patients with multiple myeloma in stable partial response after a first line therapy
• Date of first enrolment: 08/07/2009
• Target sample size: 42
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012136-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France

Key inclusion & exclusion criteria

Inclusion criteria:
1) MM which initially required a systemic therapy and received a first line treatment, conventional doses of chemotherapies or high dose chemotherapy and an autologous transplantation of hematopoietic cells, followed or not by a consolidation treatment.
2) Residual disease considered as evaluable with:
- Quantifiable serum M-protein
3) Responses which are partial (PR and VGPR) and in plateau
- Partial response should meet the IMWG uniform response criteria: a = 50% reduction from value of serum M-protein before the first line chemotherapy treatment and a reduction in 24h urinary M protein by = 90% or to < 200 mg / 24h;
- Very good partial response according to the IMWG uniform response criteria with 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg/24h; Furthermore the M protein should spike in the gamma globulin area;
- Plateau phase is defined by stable levels of M protein in serum checked 4 weeks apart on at least 3 consecutive samples.
Fluctuations ± 1 week in sampling and ± 5 % in M protein levels are allowed.
4) ECOG performance status of 0, 1 or 2
5) Clinical laboratory values at screening:
- Calculated creatinine clearance (according to MDRD) > 50 ml/min
- Platelet > 50 x 109 /l
- ANC > 1 x 109 /l
- Bilirubin levels < 1.5 ULN ; ALT and AST < 2.5 ULN (grade 1 NCI)
6) 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.
7) Signed inform consent obtained before any trial-related activities
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1) Age < 18 years old or > 75 years old
2) Previous consolidation/ maintenance therapy by Imid (thalidomide, lenalidomid) or bortezomib within the last 2 months
3) Treatment with chemotherapy, systemic corticosteroid within the previous 2 months
4) Treatment with growth factors (EPO, G- or GM-CSF) within the previous 1 month
5) MM in VGPR with a monoclonal spike in the beta globulin area
6) Radiotherapy for bone or visceral lesion within the last 3 months
7) Use of any investigational agent within the last 2 months
8) Primary or associated amyloidosis
9) Peripheral neuropathy of grade = III according to the CTCAE of the NCI
10) Abnormal cardiac status with any of the following
a) NYHA stage III or IV congestive heart failure
b) myocardial infarction within the previous 6 months
c) symptomatic cardiac arrhythmia despite treatment
11) Current active infectious disease or positive serology for HIV, HCV or positive Hbs Antigen
12) History of or current auto-immune disease
13) Serious concurrent uncontrolled medical disorder
14) History of other malignancy (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma)
15) History of allogenic hematopoietic cell or solid organ transplantation
16) Pregnant or lactating women
17) Any medical condition which is regarded by the investigator as incompatible with the study participation
18) Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple myeloma
MedDRA version: 9.1 Level: LLT Classification code 10028228 Term: Multiple myeloma

Intervention(s)

Product Name: AntiKIR (1-7F9)
Product Code: IPH2101
Pharmaceutical Form: Solution for infusion
Current Sponsor code: IPH2101
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Primary end point(s): M Protein will be measured in serum and urine:
o At Screening
o Every 4 weeks during the study period from V1-day1 to End of Study
Post study follow up: then every 3 months during 2 years according to standard practices
The primary end point will be the rate of patients achieving a response based on M- Protein levels in serum and urine sustained for at least one month.
Response will be defined:
o In patients with a serum M-protein > 5 g/l, as a reduction of at least 25% (minor response according to EBMT Appendix VI) from baseline of serum M-protein confirmed on two consecutive determinations at 4 weeks interval;
o In patients with a serum M-protein = 5 g/l, as a negative electrophoresis
In any case, a reduction = 50% or a reduction to < 200mg/ 24h in 24h urine M-protein is required.

Main Objective: The primary objective is to evaluate the clinical activity, measured by M-protein serum and urine levels, of two different dose regimens (0.2 mg/kg, leading to an intermittent saturation of NK receptors and 2mg/kg leading to a sustained saturation of NK receptors) of IPH2101 administered as a single agent in multiple myeloma patients who achieved, after the completion of any first line treatment, including conventional or high dose chemotherapies, a partial or very good partial response (PR or VGPR), stable for at least 2 months.

Secondary Objective: The secondary objectives are:
o To confirm the safety profile of the dose and administration schedules of IPH2101 in this population;
o To assess PK of two different dose regimens of IPH2101
o To evaluate the biological activity of IPH2101 on:
- KIR occupancy
- NK cell phenotype
- NK cell function
- Cytokine release
o To confirm the absence of immunogenicity of IPH2101
o To document per study and post study efficacy parameters until 2 years after the end of study :
- Overall Survival (OS)
- Duration of response (DOR)
- Progression free Survival (PFS) and Time to Progression (TTP)

Secondary ID(s)

IPH2101-201

Ethics review

Status: Approved
Approval date: 07/07/2009
Contact:

Results

• Results available: Yes
• Date Posted: 21/02/2018
• Date Completed: 05/06/2012
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-012136-33/results