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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.
Study NCT00552396   Information provided by Innate Pharma
First Received: May 21, 2007   Last Updated: August 31, 2009   History of Changes

May 21, 2007
August 31, 2009
May 2007
May 2010   (final data collection date for primary outcome measure)
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 ]
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 ]
Complete list of historical versions of study NCT00552396 on ClinicalTrials.gov Archive Site
  • 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 ]
  • To assess pharmacokinetic (PK) parameters of Anti-KIR (1-7F9) [ Time Frame: 1 year ]
  • To assess pharmacodynamic (PD) parameters of Anti-KIR (1-7F9) [ Time Frame: 1 year ]
  • To determine early signs of clinical efficacy [ Time Frame: 1 year ]
 
An Open-label, Dose-escalation Safety and Tolerability Trial Assessing Anti-KIR (1-7F9) in Subjects With Multiple Myeloma
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

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.

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.

Phase I
Interventional
Treatment, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Refractory Multiple Myeloma
Drug: Anti-KIR (1-7F9)
 
 

*   Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
 
Recruiting
30
May 2011
May 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
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
United States
 
NCT00552396
Marc Marzetto, MD/Director, Clinical Program Development, Innate Pharma
IPH2101-103
Innate Pharma
 
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
Innate Pharma
January 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP