Clinical trial NCT01638936: BT062 in Combination With Lenalidomide or Pomalidomide and Dexamethasone in Patients With Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Combination
Multiple Myeloma
Lead sponsor: Biotest Pharmaceuticals Corporation
Sponsor class: INDUSTRY
Collaborators: name: Biotest
First posted: 2012-07-12
Enrollment: 64
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: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Determination of optimal dose of BT062 (Phase I part)
timeFrame: 6 months
measure: Evaluation of response (Phase IIa part)
timeFrame: 18 months
Secondary outcomes:
measure: Qualitative toxicities of BT062 in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone
timeFrame: 24 months
measure: Pharmacokinetics of BT062 in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone
timeFrame: 24 months
measure: Assessment of Time To Event end points
timeFrame: 24 months
measure: Quantitative toxicities of BT062 in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone
timeFrame: 24 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Healthcare System
state: Florida
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: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: San Antonio
country: United States
facility: University of Texas Health Science Center
state: Texas
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Kenneth C Anderson, MD
role: STUDY_DIRECTOR
References:
citation: Kelly KR, Ailawadhi S, Siegel DS, Heffner LT, Somlo G, Jagannath S, Zimmerman TM, Munshi NC, Madan S, Chanan-Khan A, Lonial S, Chandwani S, Minasyan A, Ruehle M, Barmaki-Rad F, Abdolzade-Bavil A, Rharbaoui F, Herrmann-Keiner E, Haeder T, Wartenberg-Demand A, Anderson KC. Indatuximab ravtansine plus dexamethasone with lenalidomide or pomalidomide in relapsed or refractory multiple myeloma: a multicentre, phase 1/2a study. Lancet Haematol. 2021 Nov;8(11):e794-e807. doi: 10.1016/S2352-3026(21)00208-8. Epub 2021 Sep 13.