Phase I Dose Escalation of i.v. BI 836909 Monotherapy in Last Line Multiple Myeloma Patients
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: BI 836909
Intervention description: Intravenous Infusion of BI 836909.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No

Summary:

      The primary objective of this trial is to determine the maximum tolerated dose (MTD) of BI
      836909 administered by continuous i.v. infusion in patients with relapsed and/or refractory
      multiple myeloma. If the MTD is not reached based on safety findings, a recommended dose for
      further development will be determined. This will depend on the safety data,
      pharmacokinetic/pharmacodynamics data and potentially preliminary efficacy data. Secondary
      objectives are to document the safety and tolerability of BI 836909, to perform
      pharmacokinetic and pharmacodynamic analyses and to evaluate relevant biological effects in
      terms of parameters of efficacy.
    

Eligibility criteria:

        Inclusion criteria:

          -  Patients with a documented diagnosis of relapsed and/or refractory multiple myeloma
             who progressed after at least two prior treatment regimens, including both proteasome
             inhibitor as well as an immune-modulatory drug at time of screening

          -  must have measurable disease, defined by one or more of following at time of
             screening:

               -  a serum M protein > 0.5 g/dl measured by serum protein electrophoresis

               -  urinary M protein excretion > 200 mg/24 hours

               -  serum free light chain (FLC) measurement > 10 mg/dl, provided that the serum FLC
                  ratio is abnormal

          -  Relapse or progression of disease with an indication for therapy as per investigator´s
             judgement at time of screening

          -  ECOG Performance Status 0, 1 or 2 at time of screening

          -  Age >= 18 years at time of screening

          -  Written informed consent which is consistent with ICH_GCP guidelines and local
             legislation

          -  Able to adhere to the study visit schedule e.g. ability to come to the clinic and to
             other protocol requirements

          -  Indwelling central venous catheter or willingness to undergo intra venous central line
             placement.

        Exclusion criteria:

          -  Plasma cell leukemia

          -  Extramedullary relapse of multiple myeloma

          -  Known central nervous system involvement by multiple myeloma

          -  Last anticancer treatment < 2 weeks prior to visit 1

          -  Last treatment with a therapeutic antibody less than 6 weeks prior to visit 1

          -  Prior allogeneic stem cell transplantation or solid organ transplantation

          -  Autologous bone marrow transplantation < than 90 days at time of treatment start

          -  Last corticosteroid < 2 weeks prior to visit 1 unless the dose is <= 10 mg/day
             prednisolone or equivalent

          -  AST or ALT > 3 x upper limit of normal (CTCAE version 4.03 grade 2 or higher) at time
             of screening

          -  Total conjugated bilirubin > 1.5 x upper limit of normal (CTCAE version 4.03 grade 2
             or higher) at time of screening

          -  Absolute neutrophil count < 1.0 x 109/L (without growth factor support) at time of
             screening

          -  Platelets < 25 x 109/L (without transfusions) at time of screening

          -  Calculated GFR < 30 mL/min (Cockcroft-Gault Formula) at time of screening

          -  Clinical relevant concurrent medical disease or condition which according to the
             investigator's judgement would either compromise patient safety or interfere with the
             evaluation of the safety of the test drug, e.g. symptomatic congestive heart failure,
             unstable angina pectoris, cardiac arrhythmia requiring therapy at time of screening

          -  clinically not controlled chronic or ongoing infectious disease requiring treatment at
             the time of enrolment or within the previous two weeks

          -  Active hepatitis B or C, or laboratory evidence for a chronic infection with hepatitis
             B or C at time of screening; HIV infection at time of screening

          -  Women of childbearing potential not using highly effective method of birth control
             during the trial until one year after the last dose. Highly effective methods of birth
             control are defined as those which result in a low failure rate (i.e. less than 1% per
             year)when used consistently and correctly used such as implants, injectables, combined
             oral contraceptives, intrauterine devises (IUDs), sexual abstinence or vasectomised
             partner. Barrier methods of contraception are accepted if condom or occlusive cap is
             used together with spermicides (e.g. foam, gel). Female patients will be considered to
             be of childbearing potential unless surgically sterilized by hysterectomy or bilateral
             tubal ligation/salpingectomy, or postmenopausal (12 months with no menses without an
             alternative medical cause

          -  Male patients with partners of childbearing potential who are unwilling to use condoms
             in combination with a second medically acceptable method of contraception during the
             trial and for a minimum of 6 months after treatment

          -  Pregnancy or breast feeding

          -  Known or suspected active alcohol or drug abuse as per investigator's judgement

          -  Treatment with another investigational drug within the past four weeks before start of
             therapy or concomitantly with this trial

          -  Patients with known hypersensitivity to any component of the study drug

          -  Patients with other malignancies within 5 years at time of screening (except basal
             cell or squamous cell carcinoma of the skin or carcinoma in situ treated with curative
             therapy)

          -  Known autoimmune diseases requiring systemic treatment in past 5 years and interfering
             with evaluation of study drug

          -  Pre-existing disorders of the central nervous system