Clincosm LogoSign in Get a demo

GENESIS: 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

Sponsor
BioLineRx, Ltd. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03246529
Collaborator
(none)
136
Enrollment
18
Locations
2
Arms
93
Anticipated Duration (Months)
7.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A total of 207 subjects will be randomized into the study which will employ a double-blind placebo-controlled setting to assess the efficacy and safety of G-CSF + BL-8040 as compared to G-CSF + placebo.

Condition or Disease Intervention/Treatment Phase
  • Drug: BL-8040 1.25mg/kg + G-CSF
  • Drug: Placebo +G-CSF
 Phase 3

Detailed Description

  • Part 1: This lead-in period designed to ascertain the dose of BL-8040 will enroll a total of up to 30 subjects to an open labeled treatment to assess the efficacy, safety, PK and PD parameters of treatment with G-CSF 10 µg/kg/day and BL-8040 1.25mg/kg, per study protocol to goal collection of ≥ 6x106 CD34+ cells/kg.

  • Part 2: Following the successful completion of Part 1, a total of 177 subjects will be randomized into Part 2 of the study which will employ a double-blind placebo-controlled setting to assess the efficacy and safety of G-CSF + BL-8040 as compared to G-CSF + placebo.

Study Design

Study Type:
Interventional
Actual Enrollment :
136 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
subjects will be 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 X 109/L or ≥ 200 X 109/L).subjects will be 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 X 109/L or ≥ 200 X 109/L).
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase III, Randomized, Placebo-Controlled, Multi-Centre Study Evaluating the 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 Multiple Myeloma - The GENESIS Study
Actual Study Start Date :
Mar 23, 2018
Actual Primary Completion Date :
Dec 22, 2020
Anticipated Study Completion Date :
Dec 22, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: BL-8040 1.25mg/kg + G-CSF

double-blind placebo-controlled setting designed to assess the safety, tolerability and efficacy of G-CSF + BL-8040 as compared to G-CSF + Placebo, for stem cell mobilization in MM.

Drug: BL-8040 1.25mg/kg + G-CSF
Up to 2 SC injections of BL-8040 are anticipated during the study. Injections of G-CSF per standard of care
Active Comparator: Placebo + G-CSF

double-blind placebo-controlled setting designed to assess the safety, tolerability and efficacy of G-CSF + BL-8040 as compared to G-CSF + Placebo, for stem cell mobilization in MM.

Drug: Placebo +G-CSF
Up to 2 SC injections of Placebo are anticipated during the study. Injections of G-CSF per standard of care

Outcome Measures

Primary Outcome Measures

  1. Proportion of subjects mobilizing ≥6.0 x 106 CD34+ cells/kg with up to 2 apheresis sessions [18 months]

    Proportion of subjects mobilizing ≥6.0 x 106 CD34+ cells/kg with up to 2 apheresis sessions in preparation for auto-HCT after treatment with G-CSF + single administration of BL-8040 or G-CSF + placebo.

Secondary Outcome Measures

  1. Proportion of subjects who collect ≥2.0 x 106 CD34+ cells/kg in 1 apheresis session [18 months]

    Proportion of subjects who collect ≥2.0 x 106 CD34+ cells/kg in 1 apheresis session after treatment with G-CSF + single administration of BL-8040 or G-CSF + placebo.

  2. Proportion of subjects who collect ≥6.0 x 106 CD34+ cells/kg in 1 apheresis session [18 months]

    Proportion of subjects who collect ≥6.0 x 106 CD34+ cells/kg in 1 apheresis session after treatment with G-CSF + single administration of BL-8040 or G-CSF + placebo.

  3. Time to neutrophil engraftment, after autologous hematopoietic cell transplantation [18 months]

    Time to neutrophil engraftment, after autologous hematopoietic cell transplantation, as defined as ANC ≥0.5 x 109/L for 3 days or ≥1.0 x 109/L for 1 day following the conditioning regimen associated nadir.

  4. Time to platelet engraftment, after autologous hematopoietic cell transplantation [18 months]

    Time to platelet engraftment, after autologous hematopoietic cell transplantation, as defined as the first of 3 consecutive measurements of platelet count ≥20 x 109/L without platelet transfusion support for 7 days following the conditioning regimen associated nadir.

  5. Graft durability at 100 days post engraftment. [18 months]

    Graft durability at 100 days post engraftment, after autologous hematopoietic cell transplantation.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 78 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. Histologically confirmed Multiple Myeloma prior to enrolment and randomization.

  2. At least 1 weeks (7 days) from last induction cycle of combination/multi-agent cyto-reductive chemotherapy and no single agent chemotherapy/maintenance within 7 days (e.g. lenalidomide, pomalidomide, bortezomib, dexamethasone, etc).

  3. Eligible for Autologous Hematopoietic stem cell transplantation according at the investigator 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 .

  7. Subjects must use effective contraception.

Exclusion Criteria:

  1. Previous history of autologous or allogeneic-HCT

  2. Failed previous HSC collections or collection attempts.

  3. Patients whose apheresis product were 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:

  5. Dexamethasone: 7 days

  6. Thalidomide: 7 days

  7. Lenalidomide: 7 days

  8. Pamolidomide: 7 days

  9. Bortezomib: 7 days

  10. Carfilzomib: 7 days

  11. G-CSF: 14 days

  12. GM-CSF or Neulasta®: 21 days

  13. Combination/multi-agent cyto-reductive therapy

  14. Erythropoietin or erythrocyte stimulating agents: 30 days

  15. Eltrombopag, romiplostim or platelet stimulating agents: 30 days

  16. Carmustine (BCNU): 42 days/6 weeks

  1. Daratumumab: 28 days m. Ixazomib: 7 days

  1. Received >6 cycles lifetime exposure to Lenalidomide.

  2. Received >8 cycles of alkylating agent combinations.

  3. Received > 6 cycles of melphalan

  4. Received 3-bis(2-chloroethyl)-1nitrl.

  5. Received prior treatment with radioimmunotherapy, (e.g. radionuclides, holmium).

  6. Received marrow stimulating factors:

  7. Received G-CSF within 14 days prior to anticipated first dose of G-CSF.

  8. Received Pegfilgrastim (GM-CSF or Nulesta) within 3 weeks prior to anticipated first dose of G-CSF.

  9. Received erythrocyte of platelet stimulating agents within 30 days prior to anticipated first dose of G-CSF

  10. Plans to receive maintenance treatment within 60 days post-engraftment (e.g. Lenalidomide, Bortezomib, Pomalidomide, Thalidomide, Carfilzomib, etc.)

  11. 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.

  12. Known active CNS metastases or carcinomatous meningitis.

  13. 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.

  14. Has an active infection requiring systemic therapy or uncontrolled infection. Has a known additional malignancy that is progressing or requires active treatment. Has an underlying medical condition that would preclude study participation.

  15. 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.

  16. O2 saturation < 92% (on room air).

  17. History of unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden death.

  18. History or family history of Long QT Syndrome or Torsade de Pointes. 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 Class 2 Angina Pectoris or NYHA Heart Failure Class >2. QTcF > 470 msec, PR > 280 msec, 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.

  19. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

  20. 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.

  21. Has a known history of HIV (HIV 1/2 antibodies), active / chronic Hepatitis B or C.

Contacts and Locations

Locations

Site City State Country Postal Code
1 UCLA Medical Center Los Angeles California United States 167817
2 University of Florida Gainesville Florida United States 100278
3 University of Miami Miami Florida United States 33136
4 Loyola University Medical Center Chicago Illinois United States 60611
5 University of Maryland Baltimore Maryland United States 21201
6 The Washington University in St. Louis Saint Louis Missouri United States 63110
7 Mayo Clinic, Rochester Rochester New York United States 55902
8 University of Cincinnati Cincinnati Ohio United States 45221
9 MD Anderson Cancer Center Texas City Texas United States 77030
10 Huntsman Cancer Institute \ University of Utah Salt Lake City Utah United States 84112
11 University of Koln Köln Koln Germany 50923
12 Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases Budapest Hungary
13 University of Debrecen Debrecen Hungary 4027
14 Div. Clinicizzata di Ematologia - Policlinico Vittorio Emanuele Catania Italy 95124
15 Div. Clinicizzata di Ematologia - Policlinico Vittorio Emanuele Reggio Calabria Italy 89133
16 Hospital De La Santa Creu I Sant Pau Barcelona Spain 08041
17 Hospital University Ramon y Cajal Madrid Spain 135250
18 Hospital Universitario 12 de Octubre Madrid Spain

Sponsors and Collaborators

  • BioLineRx, Ltd.

Investigators

  • Principal Investigator: John DiPersio, MD, Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
BioLineRx, Ltd.
ClinicalTrials.gov Identifier:
NCT03246529
Other Study ID Numbers:
  • BL-8040.SCM.301
First Posted:
Aug 11, 2017
Last Update Posted:
Jun 16, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Lenograstim

Study Results

No Results Posted as of Jun 16, 2022