BT062 in Combination With Lenalidomide or Pomalidomide and Dexamethasone in Patients With Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

A Phase I/IIa Multi-dose Escalation Study of BT062 in Combination With Lenalidomide or Pomalidomide and Dexamethasone in Subjects With Relapsed or Relapsed/Refractory Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01638936
• Other study ID #: 983
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 3, 2012
• Est. completion date: October 30, 2018

Study information

• Verified date: July 2019
• Source: Biotest Pharmaceuticals Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test safety and anti-tumor activity of BT062 in combination with lenalidomide and dexamethasone to define the best doses for treating patients with relapsed and refractory multiple myeloma.

Description:

BT062 is an antibody-drug conjugate designed to bind and destroy Myeloma cells. The study drug is being given in multiple doses with standard Multiple Myeloma treatments, lenalidomide and dexamethasone, to test how well the treatments are tolerated and work together. This study is a dose escalation study with the purpose to find out the highest dose of BT062 that a subject can tolerate in combination with lenalidomide and dexamethasone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: October 30, 2018
• Est. primary completion date: October 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Diagnosis of active Multiple Myeloma according to the International Myeloma Working Group (IMWG) diagnostic criteria

• Relapsed or relapsed/refractory progressive Multiple Myeloma

• Subjects who failed at least one prior therapy (BT062/Len/dex)

• Subjects who failed at least two prior therapy (BT062/Pom/dex)

• Subjects age =18 years

• Life expectancy of =12 weeks

• Eastern Cooperative Oncology Group (ECOG) performance status (Zubrod) =2

• Normal organ and bone marrow

• Signed written informed consent in accordance with federal, local, and institutional guidelines

• Subjects must agree to follow all Guidelines from REVLIMID REMS Program or POMALYST REMS

• Women of child bearing potential (WCBP), must agree to use 2 contraceptive methods

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 adverse events (AEs) due to agents administered more than 3 weeks earlier

• Antineoplastic therapy with biological agents within 2 weeks before day 1 or within 5 drug half-lives (t½) prior to first dose, whichever time period is longer

• Concomitant antineoplastic therapies including chemotherapy, radiotherapy, or biological agents during the study

• Treatment with another investigational drug during the study or within 3 weeks before day 1 or within 5 drug half-live (t½) prior to first dose, whichever time period is longer

• Treatment with BT062 in previous studies

• Major surgery within 4 weeks before day 1 (this does not include placement of vascular access device or tumor biopsies)

• Malignancy within 3 years before day 1, other than the trial indication multiple myeloma and excluding treated non-melanoma skin cancer, superficial bladder cancer, carcinoma in-situ of the cervix and prostate carcinoma = Gleason Grade 6 with stable prostate specific antigen (PSA) levels

• Subjects with plasma cell leukemia (PCL)

• Subjects with deep vein thrombosis (DVT) and Pulmonary embolism (PE) within 3 months prior to day 1 treatment

• 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

• Acute or relevant abnormalities in electrocardiogram (ECG)

• Significant cardiac disease

• Pregnant or breast-feeding

• Positive serum or urine pregnancy test

• Hypersensitivity to the active substance or to any of the excipients for study drug BT062, or history of severe allergic or anaphylactic reaction to therapeutic proteins (e.g. reaction to vaccination or to biological therapy)

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• BT062 , intravenous administration
Dose escalation to determine dose limiting toxicities (DLTs) and/or the maximum tolerated dose (MTD)/recommended Phase II dose (RPTD) of BT062 in combination with lenalidomide/dexamethasone

Locations

Country	Name	City	State
United States	Emory University Winship Cancer Institute	Atlanta	Georgia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	The University of Chicago	Chicago	Illinois
United States	City of Hope	Duarte	California
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Mayo Clinic	Jacksonville	Florida
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Mount Sinai Medical Center	New York	New York
United States	Memorial Healthcare System	Pembroke Pines	Florida
United States	University of Texas Health Science Center	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Biotest Pharmaceuticals Corporation	Biotest

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of optimal dose of BT062 (Phase I part)	The Phase I part will follow a standard dose escalation design with at least 3 patients per dose level to define optimal dose of BT062 in combination with lenalidomide/dexamethasone. Optimal dose will be defined by dose limiting toxicities (DLT) observed during Cycle 1 (28 days).	6 months
Primary	Evaluation of response (Phase IIa part)	Response to treatment with optimal dose of BT062 (defined in Phase I part) in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone will be evaluated at baseline and at start of each Cycle (every 28 days). Response evaluation will be primarily based on assessment of M-protein and serum free light chains. If clinically required bone marrow analysis, plasmacytoma evaluation, and skeletal survey will be performed.	18 months
Secondary	Qualitative toxicities of BT062 in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone	Safety will be assessed at each visit by incidence of adverse events and by clinically significant changes in the patients physical examination, vital signs, and clinically laboratory results	24 months
Secondary	Pharmacokinetics of BT062 in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone	Pharmacokinetic parameters will be assessed from plasma by measuring intact BT062 and free maytansinoid (DM4)	24 months
Secondary	Assessment of Time To Event end points	Based on the response evaluation, the following Time To Event end points will be evaluated: Time To Progression, Progression Free Survival, Time To Next Treatment, Duration Of Response, Overall survival.	24 months
Secondary	Quantitative toxicities of BT062 in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone	Safety will be assessed at each visit by incidence of adverse events and by clinically significant changes in the patients physical examination, vital signs, and clinically laboratory results	24 months