Safety and Dose Determining Multi-dose Study of BT062 in Patients With Relapsed or Refractory Multiple Myeloma

NCT01001442 | Completed Phase 1 Results DMC

• 1 other identifier: 975
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 5

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.

Conditions

Multiple Myeloma

Keywords

Multiple myeloma; Relapsed; Refractory

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities (DLT) - Number of Participants With at Least 1 DLT

  The primary safety variable was to determine the incidence of DLTs in subjects with relapsed or relapsed/refractory multiple myeloma treated with BT062.

  Starting with first study drug administration until 30-day follow-up visit (average 4.99 months)

• Maximum Tolerated Dose (MTD)

  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. Only DLTs occurring in cycle 1 for each subject were counted in the dose escalation decisions. Three subjects were treated at the first or newest dose level as available. If none of the 3 subjects experienced a DLT during Cycle 1, three subjects could be treated at the next dose level as available. In case of a DLT the cohort was expanded to up to 6 subjects. If not more than 1 of these 6 subjects experienced a DLT during Cycle 1, a first subject could be treated at the next dose level. If 2 or more of the 6 subjects experienced a DLT during Cycle 1 the dose escalation was stopped. The highest dose level at which \< 2 of 6 subjects experienced a DLT is defined as the MTD.

  First 28-day cycle

Secondary Outcomes (4)

• Qualitative and Quantitative Toxicities of BT062

  Starting with first study drug administration until 30-day follow-up visit (average 4.99 months)

• Multi-dose Pharmacokinetics Properties of BT062 - Cmax

  Starting with first study drug administration until 30-day follow-up visit (average 4.99 months).

• 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

  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).

• Time to Progression (TTP), Progression Free Survival (PFS) and Overall Survival (OS)

  Starting with first study drug administration until death or 3 years from first study treatment.

Study Arms (1)

BT062

EXPERIMENTAL

BT062 was to be administered as single-dose IV infusions via a 0.22 μm in-line filter preferably in a forearm vein, according to medically accepted procedures on Days 1, 8, and 15 of each 28-day cycle. Alternatively BT062 may have been administered through a central venous line or a peripherally inserted central catheter (PICC). Other administration routes were only to be allowed after approval from Biotest. Each subject was to be monitored carefully for the effects of exposure to BT062. No subject was to have received more than 3 doses of BT062 per 28-day treatment cycle.

Drug: BT062

Interventions

BT062 DRUG

intravenous administration

Also known as: Indatuximab ravtansine

BT062

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Biotest Pharmaceuticals Corporation: lead
• Biotest: collaborator

Study Sites (5)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

The Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

indatuximab ravtansine

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Iris Bobenhausen
• Organization: Biotest AG

iris.bobenhausen@biotest.com

+49 6103 801

Study Officials

• Kenneth C. Anderson, MD

  Dana-Farber Cancer Institute

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2009
• First Posted: October 26, 2009
• Study Start: August 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: March 1, 2016
• Last Updated: July 30, 2019
• Results First Posted: May 8, 2018

Record last verified: 2018-01

Locations

US (5)