Multiple Myeloma
Conditions
Keywords
Combination, Multiple Myeloma
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.
Interventions
DRUGBT062 , 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
Sponsors
Biotest
Biotest Pharmaceuticals Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of response (Phase IIa part) | 18 months | 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. |
| Determination of optimal dose of BT062 (Phase I part) | 6 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Qualitative toxicities of BT062 in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone | 24 months | 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 |
| Pharmacokinetics of BT062 in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone | 24 months | Pharmacokinetic parameters will be assessed from plasma by measuring intact BT062 and free maytansinoid (DM4) |
| Assessment of Time To Event end points | 24 months | 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. |
| Quantitative toxicities of BT062 in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone | 24 months | 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 |
Countries
United States
Outcome results
None listed