A Phase III, Safety, Tolerability and Efficacy of Combination Treatment of BL-8040 and G-GSF as Compared to Placebo and G-CSF for the Mobilization of Hematopoietic Stem Cells for Autologous TransplantatIon in Subjects With MM
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: BL-8040 1.25 mg/kg + G-CSF; Placebo +G-CSF
Intervention description: Up to 2 SC injections of BL-8040 are anticipated during the study. Injections of G-CSF per standard of care; Up to 2 SC injections of Placebo are anticipated during the study. Injections of G-CSF per standard of care
Intervention MeSH terms: Lenograstim
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects were randomized using a 2:1 ratio to receive G-CSF + BL-8040 or G-CSF + Placebo, respectively. Randomization will use permuted blocks stratifying subjects by US geographical region (NorthEast, SouthEast, MidWest, SouthWest and NorthWest), remission status (CR vs. PR), and baseline platelet count (< 200 × 10^9/L or ≥ 200 × 10^9/L).
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 180.0
Sex: All
Minimum age: 18 Years
Maximum age: 78 Years
Healthy volunteers: No

Summary:

      A total of 122 subjects were randomized into the study and investigated in the double-blind
      placebo-controlled setting to assess the efficacy and safety of G-CSF + BL-8040 as compared
      to G-CSF + placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed Multiple Myeloma prior to enrolment and randomization.

          2. At least 1 week (7 days) from last induction cycle of combination/multi-agent
             cyto-reductive chemotherapy (e.g., KRD [carfilzomib, lenalidomide, dexamethasone] or
             VRD (e.g., 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.

          3. Eligible for autologous hematopoietic stem cell transplantation according to the
             Investigator's discretion.

          4. The subjects should be in first or second CR (including CR and SCR) or PR (including
             PR and VGPR).

          5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

          6. Adequate organ function at screening as defined as below:

               1. Hematology:

                    -  White blood cell counts more than 2.5 x 109/L

                    -  Absolute neutrophil count more than 1.5 x 109/L

               2. Platelet count more than 100 x109/L Renal Function:

                  • GFR value of ≥15 mL/min/1.732 calculated by MDRD equation

               3. Hepatic function:

                    -  ALT and/or AST ≤ 2.5 x ULN

                    -  Total Bilirubin ≤ 2.0 x ULN unless the subject has Gilbert disease

               4. 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

          7. Male subjects must agree to use an adequate method of contraception starting with the
             first day of G-CSF administration through 30 days after the last dose of study drug.

          8. Patients must have a signed study informed consent prior to entering the study.

        Exclusion Criteria:

          1. Previous history of autologous or allogeneic-HCT.

          2. Failed previous HSC collections or collection attempts.

          3. Taken any of the listed below concomitant medications, growth factors or stimulating
             agents within the designated washout period:

               1. Dexamethasone: 7 days;

               2. Thalidomide: 7 days;

               3. Lenalidomide: 7 days;

               4. Pamolidomide: 7 days;

               5. Bortezomib: 7 days;

               6. Carfilzomib: 7 days;

               7. G-CSF: 14 days;

               8. GM-CSF or Neulasta®: 21 days;

               9. Erythropoietin or erythrocyte stimulating agents: 30 days;

              10. Eltrombopag, romiplostim or platelet stimulating agents: 30 days;

              11. Carmustine (BCNU): 42 days/6 weeks;

              12. Daratumumab: 28 days;

              13. Ixazomib: 7 days.

          4. Received >6 cycles lifetime exposure to thalidomide or lenalidomide.

          5. Received >8 cycles of alkylating agent combinations.

          6. Received >6 cycles of melphalan.

          7. Received prior treatment with radioimmunotherapy (e.g., radionuclides, holmium).

          8. Received prior treatment wiht venetoclax.

          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 G-CSF
             administration. 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 infection requiring systemic therapy or uncontrolled infection.

         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 < 92% (on room air).

         18. Personal history or family history of Long QT Syndrome or Torsade de Pointes.

         19. History of unexplained syncope, syncope from an uncorrected cardiac etiology, or
             family history of sudden cardiac death.

         20. Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty,
             stroke, cardiac surgery, or hospitalization for congestive heart failure within 3
             months or greater than Angina Pectoris Class >2 or NYHA Heart Failure >2.

         21. ECG in screening 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 notin 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 within the projected duration
             of the trial, starting with the screening visit through 30 days after the last dose of
             study drug.

         26. Has a known history of HIV (HIV 1/2 antibodies)

         27. Has known active Hepatitis B (e.g., Hepatitis B Surface Antigen [HBsAg] reactive) or
             Hepatitis C (e.g., Hepatitis C Virus [HCV] RNA [qualitative] is detected).

         28. Untreated or unsuccessfully treated Hepatitis B or C.