Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Non-Hodgkin's Lymphoma, Non-Hodgkin Lymphoma, Hodgkin Disease, Hodgkins Disease, Hodgkin's Disease, Multiple Myeloma, Myelodysplastic Syndrome, Myeloproliferative Neoplasm
Conditions
Brief summary
Current protocols use G-CSF to mobilize hematopoietic progenitor cells from matched sibling and volunteer unrelated donors. Unfortunately, this process requires four to six days of G-CSF injection and can be associated with side effects, most notably bone pain and rarely splenic rupture. BL-8040 is given as a single SC injection, and collection of cells occurs on the same day as BL-8040 administration. This study will evaluate the safety and efficacy of this novel agent for hematopoietic progenitor cell mobilization and allogeneic transplantation based on the following hypotheses: * Healthy HLA-matched donors receiving one injection of BL-8040 will mobilize sufficient CD34+ cells (at least 2.0 x 10\^6 CD34+ cells/kg recipient weight) following no more than two leukapheresis collections to support a hematopoietic cell transplant. * The hematopoietic cells mobilized by SC BL-8040 will be functional and will result in prompt and durable hematopoietic engraftment following transplantation into HLA-identical siblings with advanced hematological malignancies using various non-myeloablative and myeloablative conditioning regimens and regimens for routine GVHD prophylaxis. * If these hypotheses 1 and 2 are confirmed after an interim safety analysis of the data, then the study will continue and include recruitment of haploidentical donors.
Interventions
Sponsors
BioLineRx, Ltd.
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
(DONOR): * Age 18 to 70 years of age. * ECOG performance status of 0 or 1. * PART 1: Donor must be a 5/6 or 6/6 HLA-matched sibling willing to donate PBSC for transplant. * PART 2: Donor must be a 5/6 or 6/6 HLA-matched sibling or 3/6 or 4/6 HLA haploidentical donor willing to donate PBSC for transplant. Haploidentical donors will be allowed to participate upon investigator decision and based on the data reached from 5/6 or 6/6 HLA matched transplant done during Part 1 of the study. * Adequate organ function defined by: * serum creatinine within normal limits or a minimum creatinine clearance (CrCl) value of ≥ 60 ml/min calculated using the Modification of Diet in Renal Disease (MDRD) Study equation * AST, ALT and total bilirubin ≤ 2x institutional upper limit of normal. * Women of childbearing potential and men must agree to use adequate contraception with two different forms, including one barrier method, during participation in the study and for 2 weeks following dosing with BL-8040. Abstinence is acceptable if this is the established and preferred contraception for the subject. * Female subjects must have a negative urine or serum pregnancy test within 10 days prior to taking study medication if of childbearing potential or must be of non-childbearing potential. 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: -≥ 45 years of age and has not had menses for \> 2 years * Amenorrheic for \> 2 years without a hysterectomy and oophorectomy and a FSH value in the postmenopausal range upon pretrial (screening) evaluation * Post-hysterectomy, oophorectomy, or tubal ligation. * Able and willing to comply with the requirements of the protocol. * Able to understand and willing to sign an IRB-approved written informed consent document. Inclusion Criteria (RECIPIENT): * Age 18 to 75 years * ECOG performance status of 0-2 (inclusive) * One of the following diagnoses: * Acute myelogenous leukemia (AML) in 1st or subsequent remission * Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission * Chronic myelogenous leukemia (CML) in chronic or accelerated phase * Non-Hodgkin lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete remission, partial remission * Chronic lymphocytic leukemia (CLL) * Multiple myeloma (MM) * Myelodysplastic syndrome (MDS) * Myeloproliferative neoplasm (MPN) excluding primary or secondary myelofibrosis * Adequate organ function defined by: * a creatinine clearance (CrCl) value of ≥ 60 ml/min by MDRD study equation * AST, ALT and a total bilirubin ≤ 2x institutional upper limit of normal. * Adequate cardiac function with a left ventricular ejection fraction ≥ 40%. * Adequate pulmonary function defined as NO severe or symptomatic restrictive or obstructive lung disease, and formal pulmonary function testing showing an FEV1 ≥50% of predicted and a DLCO ≥ 40% of predicted, corrected for hemoglobin. * Female subjects must have a negative urine or serum pregnancy test if of childbearing potential or be of non-childbearing potential. 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: \*≥ 45 years of age and has not had menses for \> 2 years * Amenorrheic for \> 2 years without a hysterectomy and oophorectomy and a FSH value in the postmenopausal range upon pretrial (screening) evaluation * Post-hysterectomy, oophorectomy, or tubal ligation. * Able to understand and willing to sign an IRB-approved written informed consent document.
Exclusion criteria
(DONOR): * Received any investigational agent within 30 days and/or 5 half-lives (of the other investigational agent), whichever is longer, of receiving BL-8040. * Active HIV or hepatitis B or C infection * Pregnant or breastfeeding. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Known allergy or hypersensitivity to any of the test compounds, materials, or contraindication to test products. * Any malignancies in the 2 years prior to baseline, excluding: basal cell carcinoma, in situ malignancy, low-risk prostate cancer, cervix cancer after curative therapy. * A comorbid condition which, in the view of the investigators, renders the subject at high risk from treatment complications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Donors That Mobilize ≥ 2 x 10^6 CD34+ Cells/kg of Recipients Weight After a Single Injection of BL-8040 After no More Than Two Leukapheresis Collections (Arm 1 - Donors Only) | Up to Day 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Neutrophil Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only) | Up to Day 28 | -Time to neutrophil engraftment is measured by determining the first of 3 consecutive measurements of neutrophil count ≥ 500/μL following conditioning regimen induced nadir. |
| Time to Platelet Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only) | Through 90 days | -Time to platelet engraftment is measured by determining the first of 3 consecutive measurements of platelet count ≥ 20,000/μL without platelet transfusion support for 7 days. |
| Number of Recipients With Primary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | Up to 1 year after transplantation | — |
| Incidence of Secondary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | Up to 1 year after transplantation | — |
| Cumulative Incidence of Grade 2-4 Acute Graft Versus Host Disease (GvHD) as Measured by Minnesota Acute GVHD Criteria (Arm 2 Recipients Only) | Day 100 | * Acute GVHD rate and worst severity is noted * 4 organ categories (skin, liver, lower GI, and upper GI) * Skin: Grade I: 1-2 , Grade II: 3, Grade III: N/A, Grade IV: 4 * Liver: Grade I: 0, Grade II: 1, Grade III: 2-4, Grade IV: N/A * Lower GI: Grade I: 0, Grade II: 1: Grade II: 2-3: Grade IV: 4 * Upper GI: Grade I: 0, Grade II: 1, Grade III: N/A, Grade IV: N/A * The cumulative incidence of grade 2-4 acute GVHD was determined using competing risk analysis. Competing risks for acute GVHD were death, relapse, and graft failure. |
| Cumulative Incidence of Chronic GvHD in Patients Who Have Undergone Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | From Day 100 through 1 year after transplantation | * Chronic GVHD rate and severity for the first 365 days after PBSC infusion will be assessed based on the NIH criteria * The cumulative incidence of chronic GVHD was determined using competing risk analysis. Competing risks for acute GVHD were death, relapse, and graft failure. |
| Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Up to 5 years | -Adverse events will be graded according to the NCI CTCAE version 4.03 |
| Incidence of CMV Reactivation After Transplantation of Hematopoietic Cells Mobilized With BL-8040 in CMV Seropositive Recipients | Up to 1 year after transplantation | -CMV reactivation will be defined as a positive test for CMV viremia as determined by an antigenemia assay or quantitative PCR that results in the administration of antiviral treatment directed against CMV |
| Cumulative Incidence of Treatment-related Mortality After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | Up to 1 year after transplantation | -Death that results from a transplant procedure related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause |
| Cumulative Incidence of Disease Relapse/Progression After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | At 1 year post-tranplantation | -Disease relapse occurs in recipients who entered transplant in CR. Progression occurs in recipients with existent disease at transplant who meet criteria for progressive disease post-transplant. A recipient will be considered relapsed when there is a recurrence of the original malignant disease after transplantation. Date of relapse/progression is defined as the date at which the first observation of hematologic, radiographic, or cytogenetic changes which signify progression/relapse is made |
| Kaplan-Meier Estimate of Event Free Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | At 2 years post-transplantation | -An event is defined as either graft failure, disease relapse as evidenced by hematologic, radiographic, or cytogenetic changes, or death. The event free survival is the time from Day 0 to occurrence of the first event. |
| Kaplan-Meier Estimate of Overall Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | At 2 years post-transplantation | -The time from Day 0 to death |
| Median Peripheral Blood CD34+ Cell Count (Arm 1 Donor Only) | At 3-4 hours after BL-8040 | — |
| Number of Participants Who Collect 5 x 106 CD34+ Cells/kg of Recipient Weight in a Single Leukapheresis and in 2 Leukapheresis Sessions (Arm 1 Donors Only) | Up to Day 2 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Donors -Donors will receive subcutaneous (SC) BL-8040 in the morning (Day 1) followed by leukapheresis approximately 180 minutes (up to 270 minutes) after the injection per institutional protocol. If the donor does not reach the collection goal for mobilization (≥ 5.0 x 10\^6 CD34+ cells/kg), a second leukapheresis will be performed on Day 2 (24 hours ± 2 hours from the BL-8040 injection) in an effort to reach a total of ≥ 5 x 10\^6 CD34+ cells/kg and at least ≥ 2 x 10\^6 CD34+ cells/kg from the combined collections. | 25 |
| Arm 2: Recipients -All or part of the leukapheresis product will be infused into the recipient per institutional guidelines. The day of the infusion will be considered Day 0; if the infusion occurs over multiple days, the final day of infusion will be considered Day 0 | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Issues with vascular acess | 1 | 0 |
| Overall Study | Mobilization failure | 0 | 3 |
Baseline characteristics
| Characteristic | Arm 1: Donors | Total | Arm 2: Recipients |
|---|---|---|---|
| Age, Continuous | 55 years | 55 years | 58 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 44 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) White | 20 Participants | 42 Participants | 22 Participants |
| Region of Enrollment United States | 25 participants | 50 participants | 25 participants |
| Sex: Female, Male Female | 7 Participants | 17 Participants | 10 Participants |
| Sex: Female, Male Male | 18 Participants | 33 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 13 / 22 |
| other Total, other adverse events | 25 / 25 | 22 / 22 |
| serious Total, serious adverse events | 0 / 25 | 12 / 22 |
Outcome results
Primary
Number of Donors That Mobilize ≥ 2 x 10^6 CD34+ Cells/kg of Recipients Weight After a Single Injection of BL-8040 After no More Than Two Leukapheresis Collections (Arm 1 - Donors Only)
Time frame: Up to Day 2
Population: This outcome measure is for Arm 1 - Donors only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Donors | Number of Donors That Mobilize ≥ 2 x 10^6 CD34+ Cells/kg of Recipients Weight After a Single Injection of BL-8040 After no More Than Two Leukapheresis Collections (Arm 1 - Donors Only) | 22 Participants |
Secondary
Cumulative Incidence of Chronic GvHD in Patients Who Have Undergone Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
* Chronic GVHD rate and severity for the first 365 days after PBSC infusion will be assessed based on the NIH criteria * The cumulative incidence of chronic GVHD was determined using competing risk analysis. Competing risks for acute GVHD were death, relapse, and graft failure.
Time frame: From Day 100 through 1 year after transplantation
Population: -Donors are not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 2: Recipients | Cumulative Incidence of Chronic GvHD in Patients Who Have Undergone Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | 0.5000 proportion of participants |
Secondary
Cumulative Incidence of Disease Relapse/Progression After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
-Disease relapse occurs in recipients who entered transplant in CR. Progression occurs in recipients with existent disease at transplant who meet criteria for progressive disease post-transplant. A recipient will be considered relapsed when there is a recurrence of the original malignant disease after transplantation. Date of relapse/progression is defined as the date at which the first observation of hematologic, radiographic, or cytogenetic changes which signify progression/relapse is made
Time frame: At 2 years post-tranplantation
Population: Donors are not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 2: Recipients | Cumulative Incidence of Disease Relapse/Progression After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | 0.273 proportion of participants |
Secondary
Cumulative Incidence of Disease Relapse/Progression After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
-Disease relapse occurs in recipients who entered transplant in CR. Progression occurs in recipients with existent disease at transplant who meet criteria for progressive disease post-transplant. A recipient will be considered relapsed when there is a recurrence of the original malignant disease after transplantation. Date of relapse/progression is defined as the date at which the first observation of hematologic, radiographic, or cytogenetic changes which signify progression/relapse is made
Time frame: At 1 year post-tranplantation
Population: Donors are not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 2: Recipients | Cumulative Incidence of Disease Relapse/Progression After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | 0.227 proportion of participants |
Secondary
Cumulative Incidence of Grade 2-4 Acute Graft Versus Host Disease (GvHD) as Measured by Minnesota Acute GVHD Criteria (Arm 2 Recipients Only)
* Acute GVHD rate and worst severity is noted * 4 organ categories (skin, liver, lower GI, and upper GI) * Skin: Grade I: 1-2 , Grade II: 3, Grade III: N/A, Grade IV: 4 * Liver: Grade I: 0, Grade II: 1, Grade III: 2-4, Grade IV: N/A * Lower GI: Grade I: 0, Grade II: 1: Grade II: 2-3: Grade IV: 4 * Upper GI: Grade I: 0, Grade II: 1, Grade III: N/A, Grade IV: N/A * The cumulative incidence of grade 2-4 acute GVHD was determined using competing risk analysis. Competing risks for acute GVHD were death, relapse, and graft failure.
Time frame: Day 100
Population: -Donors are not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 2: Recipients | Cumulative Incidence of Grade 2-4 Acute Graft Versus Host Disease (GvHD) as Measured by Minnesota Acute GVHD Criteria (Arm 2 Recipients Only) | 0.3636 proportion of participants |
Secondary
Cumulative Incidence of Treatment-related Mortality After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
-Death that results from a transplant procedure related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause
Time frame: Up to 1 year after transplantation
Population: -Donors are not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 2: Recipients | Cumulative Incidence of Treatment-related Mortality After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | 0.2273 proportion of participants |
Secondary
Incidence of CMV Reactivation After Transplantation of Hematopoietic Cells Mobilized With BL-8040 in CMV Seropositive Recipients
-CMV reactivation will be defined as a positive test for CMV viremia as determined by an antigenemia assay or quantitative PCR that results in the administration of antiviral treatment directed against CMV
Time frame: Up to 1 year after transplantation
Population: -Donors are not evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 2: Recipients | Incidence of CMV Reactivation After Transplantation of Hematopoietic Cells Mobilized With BL-8040 in CMV Seropositive Recipients | 8 Participants |
Secondary
Incidence of Secondary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
Time frame: Up to 1 year after transplantation
Population: -Donors are not evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 2: Recipients | Incidence of Secondary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | 0 Participants |
Secondary
Kaplan-Meier Estimate of Event Free Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
-An event is defined as either graft failure, disease relapse as evidenced by hematologic, radiographic, or cytogenetic changes, or death. The event free survival is the time from Day 0 to occurrence of the first event.
Time frame: At 3 years post-transplantation
Population: Donors are not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 2: Recipients | Kaplan-Meier Estimate of Event Free Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | 34.1 percentage of participants |
Secondary
Kaplan-Meier Estimate of Event Free Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
-An event is defined as either graft failure, disease relapse as evidenced by hematologic, radiographic, or cytogenetic changes, or death. The event free survival is the time from Day 0 to occurrence of the first event.
Time frame: At 2 years post-transplantation
Population: Donors are not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 2: Recipients | Kaplan-Meier Estimate of Event Free Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | 50.0 percentage of participants |
Secondary
Kaplan-Meier Estimate of Overall Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
-The time from Day 0 to death
Time frame: At 3 years post-transplantation
Population: Donors are not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 2: Recipients | Kaplan-Meier Estimate of Overall Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | 49.0 percentage of participants |
Secondary
Kaplan-Meier Estimate of Overall Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
-The time from Day 0 to death
Time frame: At 2 years post-transplantation
Population: Donors are not evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 2: Recipients | Kaplan-Meier Estimate of Overall Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | 63.6 percentage of participants |
Secondary
Median Peripheral Blood CD34+ Cell Count (Arm 1 Donor Only)
Time frame: At 3-4 hours after BL-8040
Population: Recipients are not evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Donors | Median Peripheral Blood CD34+ Cell Count (Arm 1 Donor Only) | 15 CD34/microliters |
Secondary
Number of Participants Who Collect 5 x 106 CD34+ Cells/kg of Recipient Weight in a Single Leukapheresis and in 2 Leukapheresis Sessions (Arm 1 Donors Only)
Time frame: Up to Day 2
Population: -Recipients are not evaluable for this outcome measure. -Only donors who received 1.25 mg/kg of BL-8040 were evaluable for this outcome measure (the 1st 10 donors received 1.00 mg/kg of BL-8040)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Donors | Number of Participants Who Collect 5 x 106 CD34+ Cells/kg of Recipient Weight in a Single Leukapheresis and in 2 Leukapheresis Sessions (Arm 1 Donors Only) | 9 Participants |
Secondary
Number of Recipients With Primary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
Time frame: Up to 1 year after transplantation
Population: -Donors are not evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 2: Recipients | Number of Recipients With Primary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) | 0 Participants |
Secondary
Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only)
-Adverse events will be graded according to the NCI CTCAE version 4.03
Time frame: Up to 5 years
Population: This outcome measure is for Donor Arm only.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 anemia | 17 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 bruising | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 hemoglobin increased | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 lymphocyte count decreased | 6 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 3 lymphocyte count decreased | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 lymphocyte count increased | 22 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 platelet count decreased | 22 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 weight loss | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 hypocalcemia | 10 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 hypomagnesemia | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 arthralgia | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 bone pain | 2 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 dysgeusia | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 headache | 3 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 paresthesia | 3 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 insomnia | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 sinus bradycardia | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 sinus tachycardia | 2 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 eye pain | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 watering eyes | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 nausea | 5 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 oral dysesthesia | 6 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 vomiting | 2 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 chills | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 fatigue | 3 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 fever | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 infusion related reaction | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 injection site reaction | 20 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 localized edema | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 pain | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 vibration sensation | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 allergic reaction | 20 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 papulopustular rash | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 white blood cell decreased | 2 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 A1c increased | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 hyperglycemia | 2 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 hyperkalemia | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 foot pain | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 numbness in arms | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 pain in extremity | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 dysesthesia | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 dizziness | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 dyspnea | 1 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 hypertension | 7 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 3 hypertension | 4 Participants |
| Arm 1: Donors | Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) | Grade 1/2 hypotension | 2 Participants |
Secondary
Time to Neutrophil Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only)
-Time to neutrophil engraftment is measured by determining the first of 3 consecutive measurements of neutrophil count ≥ 500/μL following conditioning regimen induced nadir.
Time frame: Up to Day 28
Population: -Donors are not evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 2: Recipients | Time to Neutrophil Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only) | 13 days |
Secondary
Time to Platelet Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only)
-Time to platelet engraftment is measured by determining the first of 3 consecutive measurements of platelet count ≥ 20,000/μL without platelet transfusion support for 7 days.
Time frame: Through 90 days
Population: -Donors are not evaluable for this outcome measure. 1 recipient was not evaluable due to no platelet nadir and 1 recipient was not evaluable due to no engraftment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 2: Recipients | Time to Platelet Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only) | 20 days |