An Open-label, Dose-escalation Safety and Tolerability Trial Assessing Anti-KIR (1-7F9) in Subjects With Multiple Myeloma

NCT00552396 | Completed Phase 1 Results DMC

• 1 other identifier: IPH2101-103
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 4

Brief Summary

Development of new treatments for diseases such as multiple myeloma is a focus for research. The research being conducted is on treatment called Anti-KIR (1-7F9), which activates the body's own cells to kill tumor cells. This is different from many other treatments where chemicals are given to kill tumor cells. The purpose of the study is to determine a safe dose of Anti-KIR (1-7F9) to administer in humans and to gain information about its effectiveness in the treatment of multiple myeloma.

Conditions

Multiple Myeloma

Keywords

multiple myeloma; Anti-KIR (1-7F9)

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of IPH2101 as Determined by Number of Participants With Dose-Limiting Toxicities (DLTs) Related to IPH2101 Treatment

  The maximum tolerated dose (MTD) is the highest dose level below the maximum administered dose (MAD) where none or 1 out of 6 subjects have a DLT.

  From start of the treatment to end of study

Secondary Outcomes (3)

• Maximum Plasma Concentration (Cmax) of IPH2101 After Cycle 1 Administration

  Anti-KIR (1-7F9) concentrations were measured prior to infusion at 0.167, 1, 3, 6, 12 and 24 hours and then on Days 7, 14 and 21 after the start of the first dose administration

• Area Under the Plasma-concentration-time Curve [AUC (INF)] of IPH2101 After Cycle 1 Administration

  Anti-KIR (1-7F9) concentrations were measured prior to infusion at 0.167, 1, 3, 6, 12 and 24 hours and then on Days 7, 14 and 21 after the start of the first dose administration

• Number of Evaluable Patients With Stable Disease. "Evaluable" is Defined as 2 Consecutive M Protein Assessments

  From start of the treatment to end of study or disease progression

Interventions

Anti-KIR (1-7F9) DRUG

human monoclonal antibody

Eligibility Criteria

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

You may qualify if:

• Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)
• Bone marrow plasmacytosis \> 10% (as determined by bone marrow aspirate) or plasmacytoma
• Relapse or progression after at least one prior systemic treatment regimen for Multiple Myeloma (MM) as evidenced by ≥ 25% increase in the M-protein as compared to the best response from the previous treatment regimen.
• a. One prior therapy for multiple myeloma, Measurable disease, as defined by persistent presence of serum and/or urine monoclonal protein or abnormal serum free light chain ratio following the prior treatment.
• a. Only for the last seven patients enrolled into the cohort 7 or Maximal Tolerated Dose (MTD).
• \. Full recovery from acute toxicities of prior anti-MM therapies. 5. Peripheral blood (Natural Killer) NK cells (Absolute CD16, 56)≥ 0.05 x 109/L (50/mm3) 6. Detectable binding of Anti-KIR (1-7F9) to subject NK cells 7. Age ≥ 18 years 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2 9. Clinical laboratory values at screening:
• serum creatinine \< grade 2 toxicity i.e. 1.5x upper limit of institutional normal value
• total bilirubin \< 1.5x upper limit of institutional normal value
• Aspartate aminotransferase (AST) \< or = 3x upper limit of institutional normal value
• Absolute Neutrophil Count (ANC) \>1.2 x109/L
• Platelets \>70x109/L

You may not qualify if:

• Known or suspected allergy to trial product or related products
• Previous participation in this trial (dosed)
• Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (appropriate methods include abstinence and the following methods: diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives)
• Male subjects who are sexually active and have not been surgically sterilized must be informed that they must either use a condom during intercourse, ensure that their partners practices contraception, or they must refrain from sexual intercourse during the study and until 1 month after completion of the trial.
• Use of an investigational agent within 30 days of the first dose of study drug (or five half-lives of any antibody).
• Current treatment with any other anti-MM therapy excluding prophylactic bisphosphonates.
• Radiotherapy against bone lesions within 4 weeks or visceral lesions within 8 weeks of Screening.
• Thalidomide or bortezomib treatment within 14 days of Screening.
• Cytotoxic chemotherapy (excluding thalidomide or bortezomib) or corticosteroid treatment within 28 days of Screening.
• Subjects with non-secretory multiple myeloma
• Subjects on dialysis
• Use of myeloid growth factor within 28 days of screening
• G-CSF treatment within 28 days of screening
• Active autoimmune disease
• Active infectious disease (e.g. HIV, chronic hepatitis, etc.) as judged by the investigator.

Sponsors & Collaborators

• Innate Pharma: lead

Study Sites (4)

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Mont Sinai Medical Center

New York, New York, 10029, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Cancer Therapy Research Center at UTHSCSA

San Antonio, Texas, 78229-4427, United States

Location

Related Publications (1)

• Benson DM Jr, Hofmeister CC, Padmanabhan S, Suvannasankha A, Jagannath S, Abonour R, Bakan C, Andre P, Efebera Y, Tiollier J, Caligiuri MA, Farag SS. A phase 1 trial of the anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma. Blood. 2012 Nov 22;120(22):4324-33. doi: 10.1182/blood-2012-06-438028. Epub 2012 Oct 1.

  PMID: 23033266 DERIVED

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 Renaud Buffet Senior Director, Clinical Development and Translational Research
• Organization: Innate Pharma

renaud.buffet@innate-pharma.fr

+33430303032

Study Officials

• Sherif Farag, MD, PhD

  Indiana University

  PRINCIPAL INVESTIGATOR

• Don Benson, Jr., MD, PhD

  Division of Haematology/Oncology - Ohio State University

  PRINCIPAL INVESTIGATOR

• Swaminathan Padmanabhan, MD

  CTRC Institute for Drug Development - University of Texas at San Antonio

  PRINCIPAL INVESTIGATOR

• Sundar Jagannath, MD

  Mount Sinai Hospital, New York

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2007
• First Posted: November 1, 2007
• Study Start: May 1, 2007
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: March 31, 2016
• Results First Posted: June 28, 2012

Record last verified: 2016-03

Locations

US (4)