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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Innate Pharma
ClinicalTrials.gov Identifier:
NCT00552396
First received: May 21, 2007
Last updated: May 24, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Anti-KIR (1-7F9)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Dose-escalation Safety and Tolerability Trial Assessing Multiple Dose Administrations of Anti-KIR (1-7F9) Human Monoclonal Antibody in Subjects With Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Innate Pharma:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of IPH2101 as Determined by Number of Participants With Dose-Limiting Toxicities (DLTs) Related to IPH2101 Treatment [ Time Frame: From start of the treatment to end of study ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Maximum Plasma Concentration (Cmax) of IPH2101 After Cycle 1 Administration [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Cmax was obtained from the plasma concentration versus time data after IV administration of IPH2101.

  • Area Under the Plasma-concentration-time Curve [AUC (INF)] of IPH2101 After Cycle 1 Administration [ Time Frame: 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 ] [ Designated as safety issue: No ]
    AUC(INF), area under the plasma concentration-time curve from zero to the last time of the last quantifiable concentration within the dosing interval was calculated for Cycle 1.

  • Number of Evaluable Patients With Stable Disease. "Evaluable" is Defined as 2 Consecutive M Protein Assessments [ Time Frame: From start of the treatment to end of study or disease progression ] [ Designated as safety issue: No ]
    Disease Response Assessment by Principal Investigator and Sponsor(Efficacy Population).Stable Disease was defined as not meeting criteria for complete response, very good partial response, partial response, or progressive disease


Enrollment: 32
Study Start Date: May 2007
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Anti-KIR (1-7F9)
    human monoclonal antibody
Detailed Description:

Trial Design:

The trial is an open-label, dose-escalation trial to determine the safety and tolerability of Anti-KIR (1-7F9) in subjects with relapsed or refractory multiple myeloma (RRMM). A 3+3 design will be employed for the first dosing cycle at each dose level. The 7 planned dose levels are 0.0003 mg/kg, 0.003 mg/kg, 0.015 mg/kg, 0.075 mg/kg, 0.3 mg/kg, 1.0 mg/kg and 3.0 mg/kg. The subjects will receive up to a total of 4 administrations of Anti-KIR (1-7F9) with a dosing interval between each administration of 4 weeks. Safety, toxicity, PK (pharmacokinetic) and PD (pharmacodynamic) obtained in the first 4 weeks after dosing per group will be the basis for dose-escalation decisions. There will be follow-up visits every week the one month after the first administration and every two weeks following the second, third and fourth administrations. After the last administration there will be follow-up visits every month until KIR occupancy is no longer detected.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.)
  2. Bone marrow plasmacytosis > 10% (as determined by bone marrow aspirate) or plasmacytoma
  3. 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.

3a. 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).

4. 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

Exclusion Criteria:

  1. Known or suspected allergy to trial product or related products
  2. Previous participation in this trial (dosed)
  3. 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)
  4. 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.
  5. Use of an investigational agent within 30 days of the first dose of study drug (or five half-lives of any antibody).
  6. Current treatment with any other anti-MM therapy excluding prophylactic bisphosphonates.
  7. Radiotherapy against bone lesions within 4 weeks or visceral lesions within 8 weeks of Screening.
  8. Thalidomide or bortezomib treatment within 14 days of Screening.
  9. Cytotoxic chemotherapy (excluding thalidomide or bortezomib) or corticosteroid treatment within 28 days of Screening.
  10. Subjects with non-secretory multiple myeloma
  11. Subjects on dialysis
  12. Use of myeloid growth factor within 28 days of screening
  13. G-CSF treatment within 28 days of screening
  14. Active autoimmune disease
  15. Active infectious disease (e.g. HIV, chronic hepatitis, etc.) as judged by the investigator.
  16. New York Heart Association (NYHA) class III-IV heart failure
  17. Severe neurological / psychiatric disorder as judged by the investigator
  18. Clinical evidence of an active second malignancy, with the exception of basal cell carcinoma or in situ carcinoma of cervix.
  19. Subjects with a history of allogenic transplantation.
  20. Subject who have undergone autologous transplantation within the last 3 months.
  21. Mental incapacity or inadequate understanding of English.
  22. Any serious medical condition that in the opinion of the investigator, disqualifies the subject for inclusion in the trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00552396

Locations
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
United States, New York
Mont Sinai Medical Center
New York City, New York, United States, 10029
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Texas
Cancer Therapy Research Center at UTHSCSA
San Antonio, Texas, United States, 78229-4427
Sponsors and Collaborators
Innate Pharma
Investigators
Principal Investigator: 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
  More Information

Additional Information:
No publications provided by Innate Pharma

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Innate Pharma
ClinicalTrials.gov Identifier: NCT00552396     History of Changes
Other Study ID Numbers: IPH2101-103
Study First Received: May 21, 2007
Results First Received: March 2, 2012
Last Updated: May 24, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Innate Pharma:
multiple myeloma
Anti-KIR (1-7F9)

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014