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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

Phase 1
18 Years
Not Enrolling
Multiple Myeloma

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Trial Information

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

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.

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

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

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

- 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

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

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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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.

Outcome Time Frame:

From start of the treatment to end of study

Safety Issue:


Principal Investigator

Sherif Farag, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Indiana University


United States: Food and Drug Administration

Study ID:




Start Date:

May 2007

Completion Date:

January 2011

Related Keywords:

  • Multiple Myeloma
  • multiple myeloma
  • Anti-KIR (1-7F9)
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



Indiana University Cancer Center Indianapolis, Indiana  46202-5265
Ohio State University Medical Center Columbus, Ohio  43210
Mont Sinai Medical Center New York City, New York  10029
Cancer Therapy Research Center at UTHSCSA San Antonio, Texas  78229-4427