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An Open-Label, Dose-Escalation Safety and Tolerability Trial Assessing Anti-KIR (1-7F9) in Subjects With Multiple Myeloma
This study is currently recruiting participants.
Verified by Innate Pharma, January 2009
First Received: May 21, 2007   Last Updated: June 23, 2009   History of Changes
Sponsored by: Innate Pharma
Information provided by: Innate Pharma
ClinicalTrials.gov Identifier: NCT00552396
  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
Refractory Multiple Myeloma
Drug: Anti-KIR (1-7F9)
Phase I

Study Type: Interventional
Study Design: Treatment, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
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:
  • To determine the safety and tolerability of human Anti-KIR (1-7F9), a fully human mAb, in subjects with relapsed or refractory multiple myeloma (MM) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess pharmacokinetic (PK) parameters of Anti-KIR (1-7F9) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To assess pharmacodynamic (PD) parameters of Anti-KIR (1-7F9) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To determine early signs of clinical efficacy [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: May 2007
Estimated Study Completion Date: May 2011
Estimated Primary Completion Date: May 2010 (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. 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 and PD 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 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 MTD.

  4. Full recovery from acute toxicities of prior anti-MM therapies.
  5. Peripheral blood 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
    • AST < or = 3x upper limit of institutional normal value
    • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00552396

Contacts
Contact: Marc Marzetto, MD +33 (0)9 77 40 40 41 marc.marzetto@innate-pharma.fr
Contact: Marlena Griffin (512) 904-9492 marlena.griffin@aaipharma.com

Locations
United States, Indiana
Indiana University Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Principal Investigator: Sherif Farag, MD, PhD            
Sub-Investigator: Rafat Abonour, MD            
Sub-Investigator: Attaya Suvannasankha, MD            
United States, Ohio
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Principal Investigator: Don M Benson, MD, PhD            
Sub-Investigator: John C Byrd, MD            
Sub-Investigator: Craig C Hofmeister, MD            
United States, Texas
Cancer Therapy Research Center at UTHSCSA Recruiting
San Antonio, Texas, United States, 78229-4427
Principal Investigator: Swaminathan Padmanabhan, MD            
Sub-Investigator: Andrew J Brenner, MD            
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
  More Information

Additional Information:
No publications provided

Responsible Party: Innate Pharma ( Marc Marzetto, MD/Director, Clinical Program Development )
Study ID Numbers: IPH2101-103
Study First Received: May 21, 2007
Last Updated: June 23, 2009
ClinicalTrials.gov Identifier: NCT00552396     History of Changes
Health Authority: United States: Food and Drug Administration

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

Study placed in the following topic categories:
Immunoproliferative Disorders
Immunologic Factors
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Vascular Diseases
Paraproteinemias
Hemostatic Disorders
Multiple Myeloma
Antibodies, Monoclonal
Antibodies
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoglobulins
Neoplasms, Plasma Cell

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

ClinicalTrials.gov processed this record on July 06, 2009