Evaluation of Activity, Safety and Pharmacology of IPH2101 a Human Monoclonal Antibody in Patients With Multiple Myeloma

NCT00999830 | Completed Phase 2 Results DMC

• 1 other identifier: IPH2101-201
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 9

Brief Summary

This is an open randomised phase II study evaluating the anti-tumour activity, safety and pharmacology of two dose regimens of IPH2101, a human monoclonal anti-KIR antibody, in patients with multiple myeloma in stable partial response after a first line therapy.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Rate of Patients Achieving a Response Based on M-protein or Free Light Chains

  Response was defined: * In patients with a serum M-protein \> 5 g/l, as a reduction of at least 25% (minor response according to European society for Blood and Marrow Transplantation (EBMT)) from baseline of serum M-protein confirmed on two consecutive determinations at 4 weeks interval; * In patients with a serum M-protein ≤ 5 g/l and ≥ 3g/l, as a negative electrophoresis * In patients with serum M-protein \< 3 g/l but a measurable involved serum free light chains ≥ 100 mg/l and an abnormal Free Light Chains ratio (\<0.26 or \> 1.65), as a ≥ 50 % decrease in the difference between involved and uninvolved Free Light Chains levels.

  From the start of the treatment to the End of Study and during the post study follow up during 2 years according to standard practices

Secondary Outcomes (2)

• Biological Activity of IPH2101 on Killer Immunogloblin Like Receptors (KIR) Occupancy at End of Treatment

  From the start up to the end of study (15 months)

• Safety Assessment

  from screening visit to the End of Study (at each study visit)

Study Arms (2)

IPH 2101 0.2 mg/kg

EXPERIMENTAL

One infusion of IPH2101 every 4 weeks at the dose of 0.2 mg/kg by intravenous route over 1 hour, for 4 or up to 8 cycles.

Drug: IPH2101

IPH2101 2.0 mg/kg

EXPERIMENTAL

One infusion of IPH2101 every 4 weeks at the dose of 2 mg/kg by intravenous route over 1 hour, for 4 or up to 8 cycles.

Drug: IPH2101

Interventions

IPH2101 DRUG

One infusion of IPH2101 every 4 weeks

Also known as: Fully human anti-KIR monoclonal antibody (1-7F9)

IPH 2101 0.2 mg/kg; IPH2101 2.0 mg/kg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Residual disease considered as evaluable with:
• Quantifiable serum M-protein: ≥ 3 g/l, except for spike in the beta globulin area. In this particular case serum M-protein is considered quantifiable if ≥ 10g/l
• If serum M-protein is \< 3g/l, measurable involved Free Light Chains ≥ 100 mg/l and an abnormal Free Light chains ratio (\<0.26 or \> 1.65)
• 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 :
• For patients with serum M-protein ≥ 3g/l: stable levels of M-protein in serum during at least 2 months checked on at least 3 consecutive samples, with the third evaluation performed within 4 weeks before study entry. Fluctuations of ± 25 % and ± 2 g/l in Serum M-protein levels are allowed.
• For Patients with serum M-protein \< 3g/l: stable levels Free Light Chains in serum during at least 2 months checked on at least 3 consecutive samples, with the third evaluation performed within 4 weeks before study entry. Fluctuations of ± 25 % of involved serum Free Light Chain are allowed.
• ECOG performance status of 0, 1 or 2.
• Clinical laboratory values at screening:
• Calculated creatinine clearance (according to MDRD) \> 50 ml/min
• Platelet \> 50 x 109 /l
• ANC \> 1 x 109 /l

You may not qualify if:

• Age \< 18 years old or \> 75 years old
• Previous consolidation/ maintenance therapy by Imid (thalidomide, lenalidomid) or bortezomib within the last 2 months
• Treatment with chemotherapy, systemic corticosteroid within the previous 2 months
• Treatment with growth factors (EPO, G- or GM-CSF) within the previous 1 month
• Radiotherapy for bone or visceral lesion within the last 3 months
• Use of any investigational agent within the last 2 months
• Primary or associated amyloidosis
• Peripheral neuropathy of grade ≥ III according to the CTCAE of the NCI
• Abnormal cardiac status with any of the following
• NYHA stage III or IV congestive heart failure
• myocardial infarction within the previous 6 months
• symptomatic cardiac arrhythmia despite treatment
• Current active infectious disease or positive serology for HIV, HCV or positive Hbs Antigen
• History of or current auto-immune disease
• Serious concurrent uncontrolled medical disorder

Sponsors & Collaborators

• Innate Pharma: lead

Study Sites (9)

C.H.R.U. de Caen - Hôpital Bretonneau

Caen, 14033, France

Location

CHU Dijon

Dijon, 21079, France

Location

CHRU Lille

Lille, 59037, France

Location

Hôpital Dupuytren

Limoges, 87042, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

CHU Nancy

Nancy, 54511, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Hôpital Saint Antoine

Paris, 75012, France

Location

C.H.R.U. de Tours

Tours, 37044, France

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

IPH-2101

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr Michel ATTAL
• Organization: HOPITAL DE PURPAN Service Hematologie

attal.m@chu-toulouse.fr

+33 (0)5.61.77.77.84

Study Officials

• Michel ATTAL, MD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2009
• First Posted: October 22, 2009
• Study Start: September 1, 2009
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2013
• Last Updated: March 24, 2016
• Results First Posted: March 24, 2016

Record last verified: 2014-04

Locations

FR (9)