Clinical trial NCT01001442: Safety and Dose Determining Multi-dose Study of BT062 in Patients With Relapsed or Refractory Multiple Myeloma
Official title: A Phase I/IIa Multi-Dose Escalation Study to Evaluate Maximum Tolerated Dose (MTD), Pharmacokinetics (PK), Safety and Efficacy of BT062 in Subjects With Relapsed or Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
Relapsed
Refractory
Lead sponsor: Biotest Pharmaceuticals Corporation
Sponsor class: INDUSTRY
Collaborators: name: Biotest
First posted: 2009-10-26
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This Phase I/IIa clinical study is to test safety and anti-tumor activity of BT062 to define the best dose in treating patients with relapsed or refractory multiple myeloma with multiple doses of BT062.

Detailed description: Phase I/IIa, open-label, 3 + 3 multi-dose escalation study. The Phase I part of the study was to include the dose escalation cohort; a conventional dose escalation design, following 3 + 3 rules was chosen to define the MTD.

The Phase IIa part was to include the MTD/recommended phase II dose (RPTD) expansion cohort in which descriptive statistical methods for evaluation of response, time to event endpoints, and safety were to be performed.

35 subjects in the Safety population, 34 subjects in the ITT and PP populations.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of active multiple myeloma according to the International Myeloma Working Group diagnostic criteria
* Relapsed or relapsed/refractory multiple myeloma
* Previous treatment with both an immunomodulator and a proteosome inhibitor therapy
* Age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status (Zubrod) ≤ 2
* Ability to understand and willingness to sign a written informed consent document
* Ability to adhere with the study visit schedule and other protocol procedures
* Life expectancy of ≥ 12 weeks
* Normal organ and marrow function

Exclusion Criteria:

* Chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to day 1 or those who have not recovered from AEs due to agents administered more than 3 weeks earlier
* Treatment with another investigational agent during the study or within 4 weeks before day 1
* Major surgery within 4 weeks before day 1 (this does not include placement of vascular access device or tumor biopsies)
* Antineoplastic therapy with biological agents within 2 weeks before day 1
* Known HAHAs, HACAs, or HAMAs in response to previous MAb therapy
* Previous treatment with BT062
* Malignancy within 3 years before day 1, other than the trial indication multiple myeloma and excluding treated non-melanoma skin cancer, superficial bladder cancer and carcinoma in-situ of the cervix
* Severe diseases of skin, colon, esophagus, or eye within 1 year before day 1, as judged by the Investigator
* Severe infections necessitating use of antibiotics / antivirals during the screening period
* Clinically relevant active infection including active hepatitis B or C or human immunodeficiency virus (HBV, HCV, or HIV) or any other concurrent disease which, in the judgment of the investigator, would make the subject inappropriate for enrollment into this study
* Acute or relevant abnormalities in electrocardiogram (ECG), as judged by the Investigator. These abnormalities can be defined as recent myocardial infarction, uncontrolled cardiac arrhythmias and/or pronounced disturbances of the electrical conduction system of the heart.
* Significant cardiac disease such as recent myocardial infarction (≤ 6 months prior to day 1), unstable angina, uncontrolled congestive heart failure, uncontrolled hypertension (recurrent or persistent increases in systolic blood pressure ≥ 180 mm Hg or diastolic blood pressure ≥ 110 mm Hg), uncontrolled cardiac arrhythmias, grade 3 (Lown Criteria) or greater cardiac toxicity from prior chemotherapy
* History of clinically significant drug or alcohol abuse
* Unwillingness or inability to adhere to the requirements of the study
* Concomitant therapy with corticosteroids (except as indicated in low dose for other medical conditions such as inhaled steroid for asthma, topical use, or as premedication for administration of certain medications (including BT062) or blood products and for treatment of infusion reactions if needed)
* Concomitant antineoplastic therapies including chemotherapy, radiotherapy, or biological agents during the study
* Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he or she are included in the study
* Breast-feeding
* Unwillingness to use an effective contraceptive method during the study and at least 3 months after administration of study drug - unless subject is naturally infertile. (Acceptable contraceptive methods include oral or injectable contraceptives, intrauterine devices (IUD), double-barrier method, contraceptive patch, surgical sterilization, or condoms).
* Positive serum or urine pregnancy test

Primary outcomes:
measure: Dose Limiting Toxicities (DLT) - Number of Participants With at Least 1 DLT
timeFrame: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months)
measure: Maximum Tolerated Dose (MTD)
timeFrame: First 28-day cycle
Secondary outcomes:
measure: Qualitative and Quantitative Toxicities of BT062
timeFrame: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months)
measure: Multi-dose Pharmacokinetics Properties of BT062 - Cmax
timeFrame: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months).
measure: Anti-tumor Activity of BT062 in Subjects With Relapsed or Relapsed/Refractory Multiple Myeloma by Number of Participants With Objective Response(ORR) and/or Clinial Benefit(CBR) Based on the International Myeloma Working Group Uniform Response Criteria
timeFrame: On day 1 of each treatment cycle (on a monthly basis) starting with first study drug administration until Close Out visit (average 3.84 months).
measure: Time to Progression (TTP), Progression Free Survival (PFS) and Overall Survival (OS)
timeFrame: Starting with first study drug administration until death or 3 years from first study treatment.
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: The Mount Sinai School of Medicine
state: New York
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Kenneth C. Anderson, MD
role: STUDY_DIRECTOR
References: