Hematopoietic Stem Cell mobilization in Multiple Myeloma MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: BL-8040
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: motixafortide (pINN)
CAS Number: 664334-36-5
Current Sponsor code: BL-8040
Other descriptive name: BKT
4F-benzoyl-TN14003
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 36500-
Pharmaceutical form of the placebo: Powder for solution for injection
Route
Sponsors
BioLineRx Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must be between the ages of 18 and 78 years. 2. Patients must have a signed study informed consent prior to entering the study. 3. Histologically confirmed Multiple Myeloma prior to enrollment and randomization. 4. At least 1 week (7 days) from last induction cycle of combination/multi-agent chemotherapy (e.g. KRD [carfilzomib, lenalidomide, dexamethasone] or VRD [bortezomib, lenalidomide, dexamethasone]) or last single agent chemotherapy (e.g. lenalidomide, pomalidomide, bortezomib, dexamethasone, etc) prior to the first dose of G-CSF for mobilization. 5. Eligible for Autologous Hematopoietic stem cell transplantation according to the investigator’s discretion. 6. The subjects should be in first or second CR (including CR and SCR) or PR (including PR and VGPR). 7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 8. Adequate organ function at baseline as defined below: a. Hematology: • White blood cell count more than 2.5 x 10^9/L, • Absolute neutrophil count more than 1.5 x 10^9/L • Platelet count more than 100 x10^9/L b. Renal Function: • Serum creatinine =2.2 mg/dL or creatinine clearance (CrCl) value of = 50 ml/min by MDRD equation, whichever is more stringent. c. Hepatic function: • ALT and/or AST = 2.5 x ULN • Total Bilirubin = 2.0 x ULN unless the subject has Gilbert disease d. Coagulation test: • INR or PT: =1.5xULN unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants • aPTT: =1.5xULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants 9. Subjects must use effective contraception: a. Female subjects must be of non-childbearing potential or, if of childbearing potential, must have a negative urine or serum pregnancy test within 72 hours prior to taking study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the subject to be eligible. Non-childbearing potential is defined as (by other than medical reasons): • =45 years of age and has not had menses for over 2 years. • Amenorrheic for > 2 years without a hysterectomy and oophorectomy and a Follicle Stimulating Hormone (FSH) value in the postmenopausal range upon pre-trial (screening) evaluation. • Post hysterectomy, bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation at least 6 weeks prior to screening. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure otherwise the subject must be willing to use two adequate barrier methods throughout the study, starting with the screening visit through 120 days after the last dose of study therapy. Information must be captured appropriately within the site's source documents. b. Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 30 days after the last dose of study drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 97 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: 1. Previous history of autologous or allogeneic-HCT. 2. Failed previous HSC collections or collection attempts. 3. Patients whose apheresis product will have to be further selected and purified. 4. Taken any of the listed below concomitant medications, growth factors or stimulating agents within the designated washout period: a. Dexamethasone: 7 days b. Thalidomide: 7 days c. Lenalidomide: 7 days d. Pamolidomide: 7 days e. Bortezomib: 7 days f. Carfilzomib: 7 days g. G-CSF: 14 days h. GM-CSF or Neulasta®: 21 days i. Erythropoietin or erythrocyte stimulating agents: 30 days j. Eltrombopag, romiplostim or platelet stimulating agents: 30 days k. Carmustine (BCNU): 42 days/6 weeks l. Daratumumab-28 days 5. Received >6 cycles lifetime exposure to Lenalidomide. 6. Received >8 cycles of alkylating agent combinations 7. Received > 6 cycles of melphalan. 8. Received prior treatment with radioimmunotherapy, (e.g. radionuclides, holmium). 9. Plans to receive maintenance treatment within 60 days post-engraftment (e.g. Lenalidomide, Bortezomib, Pomalidomide, Thalidomide, Carfilzomib, etc.). 10. Has received a live vaccine within 30 days of the planned start of study therapy. Seasonal flu vaccines that do not contain live virus are permitted. 11. Known active CNS metastases or carcinomatous meningitis. 12. A history of allergic reactions attributed to compounds of similar chemical or biologic composition to BL-8040, G-CSF, or other agents used in the study. 13. Has an active or uncontrolled infection requiring systemic therapy. 14. Has a known additional malignancy that is progressing or requires active treatment. 15. Has an underlying medical condition that would preclude study participation. 16. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 17. O2 saturation 2 or NYHA Heart Failure Class >2. 21. ECG at screening or baseline showing QTcF > 470 msec and/or PR > 280 msec. 22. Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block, unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities. 23. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator. 24. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 25. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 30 days after the last dose of trial treatment. Women with a positive pregnancy test within 72 hours from baseline. 26. Has a known
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the superiority of one dose of BL-8040 + G-CSF over placebo + G-CSF to mobilize =6.0 x 10^6 CD34+ cells/kg in up to 2 apheresis sessions in preparation for autologous hematopoietic cell transplantation (auto-HCT) in MM subjects.;Secondary Objective: - To demonstrate the superiority of one dose of BL-8040 + G-CSF over placebo + G-CSF to mobilize =2.0 x 10^6 CD34+ cells/kg in 1 apheresis session in preparation for autologous hematopoietic cell transplantation (auto-HCT) in MM subjects. - To demonstrate the superiority of one dose of BL-8040 + G-CSF over placebo + G-CSF to mobilize =6.0 x 10^6 CD34+ cells/kg in 1 apheresis session in preparation for autologous hematopoietic cell transplantation (auto-HCT) in MM subjects. - To descriptively assess the comparability between the effects of BL-8040 + G-CSF and placebo + G-CSF in time to neutrophil engraftment, platelet engraftment and the later of the two. - To descriptively assess the comparability between the effects of BL-8040 + G-CSF and placebo + G-CSF on graft durability at 100 days, 6 and 12 months post-engraftment. - To demonstrate that the use of (one or two doses) BL-8040 + G-CSF over placebo + G-CSF results in a reduction in resource use and cost savings.;Primary end point(s): Proportion of subjects mobilizing =6.0 x 10^6 CD34+ cells/kg with up to 2 apheresis sessions in preparation for auto-HCT after G-CSF + single administration of BL-8040 or Placebo + G-CSF.;Timepoint(s) of evaluation of this end point: June 2020 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Proportion of subjects who collect =2.0 x 10^6 CD34+ cells/kg in 1 apheresis session - Proportion of subjects who collect =6.0 x 10^6 CD34+ cells/kg in 1 apheresis session -Economic endpoints: resource utilization until engraftment and 100 days post engraftment;Timepoint(s) of evaluation of this end point: June 2020 | — |
Countries
Czech Republic, Germany, Hungary, Italy, Spain, United States
Contacts
Public ContactClinical Trial Manager
BioLineRx Ltd.
Outcome results
None listed