Safety and Efficacy of BL-8040 for the Mobilization of Do... | NCT02639559

Name	Class
BioLineRx, Ltd.	INDUSTRY

Label	Type	Description	Intervention Names
Arm 1: Donors	Experimental	-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.	Drug: BL-8040 Procedure: Leukapheresis
Arm 2: Recipients	Experimental	-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	Procedure: Hematopoietic cell transplant

Name	Type	Description	Arm Group Labels	Other Names
BL-8040	Drug		Arm 1: Donors
Leukapheresis

Measure	Description	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

Measure	Description	Time Frame
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	Up to 5 years
Time to Neutrophil Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only)

Eligibility Module

Eligibility Criteria

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.

Exclusion Criteria (RECIPIENT):

Recipient must not have received any investigational drug within 30 days of starting conditioning treatment.
Pregnant or breastfeeding.
Active HIV or hepatitis B or C infection.
Any medical condition which, in the opinion of the clinical investigator, would interfere with the evaluation of the patient. Subjects with a clinically significant or unstable medical or surgical condition or any other condition that cannot be well-controlled by the allowed medications permitted in the study protocol that would preclude safe and complete study participation, as determined by medical history, physical examinations, ECG, laboratory tests, or chest-X-ray and according to the investigator's judgment.

Name	Affiliation	Role
Geoffrey Uy, M.D.	Washington University School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Northside Hospital Cancer Institute		Atlanta	Georgia	30342	United States
Washington University School of Medicine

Label	URL
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine	View source

ID	Title	Description
FG000	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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Oct 25, 2017

ID	Title	Description
BG000	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.
BG001	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
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00025 BG00125 BG00250

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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)

This outcome measure is for Arm 1 - Donors only.

Posted

Count of Participants

Participants

Up to Day 2

ID	Title	Description
OG000	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.
OG001	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

Units	Counts
Participants	OG00024 OG0010

Title

Denominators

Categories

Title	Measurements
	OG00022

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

This outcome measure is for Donor Arm only.

Posted

Count of Participants

Participants

Up to 5 years

ID	Title	Description
OG000	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.
OG001	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

Units	Counts

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.

-Donors are not evaluable for this outcome measure.

Posted

Median

Full Range

days

Up to Day 28

ID	Title	Description
OG000	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.
OG001	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

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.

-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.

Posted

Median

Full Range

days

Through 90 days

ID	Title	Description
OG000	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.
OG001	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

Secondary

Number of Recipients With Primary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)

-Donors are not evaluable for this outcome measure.

Posted

Count of Participants

Participants

Up to 1 year after transplantation

ID	Title	Description
OG000	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.
OG001	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

Units	Counts
Participants

Secondary

Incidence of Secondary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)

-Donors are not evaluable for this outcome measure.

Posted

Count of Participants

Participants

Up to 1 year after transplantation

ID	Title	Description
OG000	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.
OG001	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

Units	Counts
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.

-Donors are not evaluable for this outcome measure.

Posted

Number

95% Confidence Interval

proportion of participants

Day 100

ID	Title	Description
OG000	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.
OG001	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

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.

-Donors are not evaluable for this outcome measure.

Posted

Number

95% Confidence Interval

proportion of participants

From Day 100 through 1 year after transplantation

ID	Title	Description
OG000	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.
OG001	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

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)

-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)

Posted

Count of Participants

Participants

Up to Day 2

ID	Title	Description
OG000	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.
OG001	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

Units

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

-Donors are not evaluable for this outcome measure.

Posted

Count of Participants

Participants

Up to 1 year after transplantation

ID	Title	Description
OG000	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.
OG001	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

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

-Donors are not evaluable for this outcome measure.

Posted

Number

95% Confidence Interval

proportion of participants

Up to 1 year after transplantation

ID	Title	Description
OG000	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.
OG001	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

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

Donors are not evaluable for this outcome measure.

Posted

Number

95% Confidence Interval

proportion of participants

At 1 year post-tranplantation

ID	Title	Description
OG000	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.
OG001	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

Secondary

Cumulative Incidence of Disease Relapse/Progression After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)

Donors are not evaluable for this outcome measure.

Posted

Number

95% Confidence Interval

proportion of participants

At 2 years post-tranplantation

ID	Title	Description
OG000	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.
OG001	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

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.

Donors are not evaluable for this outcome measure.

Posted

Number

percentage of participants

At 2 years post-transplantation

ID	Title	Description
OG000	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.
OG001	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

Secondary

Kaplan-Meier Estimate of Event Free Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)

Donors are not evaluable for this outcome measure.

Posted

Number

percentage of participants

At 3 years post-transplantation

ID	Title	Description
OG000	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.
OG001	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

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

Donors are not evaluable for this outcome measure.

Posted

Number

percentage of participants

At 2 years post-transplantation

ID	Title	Description
OG000	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.
OG001	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

Units	Counts

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

Donors are not evaluable for this outcome measure.

Posted

Number

percentage of participants

At 3 years post-transplantation

ID	Title	Description
OG000	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.
OG001	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

Units	Counts

Secondary

Median Peripheral Blood CD34+ Cell Count (Arm 1 Donor Only)

Recipients are not evaluable for this outcome measure.

Posted

Median

Full Range

CD34/microliters

At 3-4 hours after BL-8040

ID	Title	Description
OG000	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.
OG001	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

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment	EG00017 affected25 at risk EG0010 affected22 at risk
Febrile neutropenia	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0017 affected22 at risk
Acute systolic heart failure	Cardiac disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Chest pain-cardiac	Cardiac disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Sinus brachycardia	Cardiac disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Sinus tachycardia	Cardiac disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected25 at risk EG0010 affected22 at risk
Eye pain	Eye disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Watering eyes	Eye disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Abdominal pain	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Colitis	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Diarrhea	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Esophagitis	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Mucositis oral	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0017 affected22 at risk
Nausea	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0005 affected25 at risk EG0012 affected22 at risk
Oral dysesthesia	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0006 affected25 at risk EG0010 affected22 at risk
Vomiting	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected25 at risk EG0010 affected22 at risk
Chills	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Edema limbs-anasarca	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Fatigue	General disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected25 at risk EG0012 affected22 at risk
Fever	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Infusion related reaction	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Injection site reaction	General disorders	CTCAE (4.0)	Systematic Assessment	EG00020 affected25 at risk EG0010 affected22 at risk
Localized edema	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Pain	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Vibration sensation	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Hepatic failure	Hepatobiliary disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Allergic reaction	Immune system disorders	CTCAE (4.0)	Systematic Assessment	EG00020 affected25 at risk EG0010 affected22 at risk
Bacteremia-Klebsiella pneumoniae	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Bacteremia-VRE	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Catheter related infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Clostridium difficile	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0012 affected22 at risk
Lung infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0012 affected22 at risk
Oral thrush	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Papulopustular rash	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Skin infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Urinary tract infection	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0012 affected22 at risk
Bruising	Injury, poisoning and procedural complications	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Alanine aminotransferase increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0012 affected22 at risk
Aspartate aminotransferase increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Blood bilirubin increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
GGT increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Hemoglobin increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Lymphocyte count decreased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0007 affected25 at risk EG0010 affected22 at risk
Lymphocyte count increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG00022 affected25 at risk EG0010 affected22 at risk
Platelet count decreased	Investigations	CTCAE (4.0)	Systematic Assessment	EG00022 affected25 at risk EG0010 affected22 at risk
Weight loss	Investigations	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
White blood cell decreased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0002 affected25 at risk EG0010 affected22 at risk
A1c increased	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Dehydration	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Hypercalcemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected25 at risk EG0014 affected22 at risk
Hyperkalemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0012 affected22 at risk
Hypermagnesemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Hyperuricemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0012 affected22 at risk
Hypocalcemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG00010 affected25 at risk EG0010 affected22 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0014 affected22 at risk
Hypomagnesemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Hyponatremia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Hypophosphatemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0016 affected22 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Back pain	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0012 affected22 at risk
Bone pain	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected25 at risk EG0010 affected22 at risk
Foot pain	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Numbness in arms	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Dizziness	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Dysesthesia	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Dysgeusia	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Headache	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected25 at risk EG0013 affected22 at risk
Paresthesia	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected25 at risk EG0010 affected22 at risk
Syncope	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Insomnia	Psychiatric disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Cystitis noninfective	Renal and urinary disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Renal failure	Renal and urinary disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected22 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0014 affected22 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Pulmonary edema	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Sore throat	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Scrotal pruritus	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk
Hypertension	Vascular disorders	CTCAE (4.0)	Systematic Assessment	EG00011 affected25 at risk EG00111 affected22 at risk
Hypotension	Vascular disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected25 at risk EG0011 affected22 at risk
Veno-occlusive disease	Vascular disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected22 at risk

ID	Term
D015470	Leukemia, Myeloid, Acute
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma
D015464	Leukemia, Myelogenous, Chronic, BCR-ABL Positive
D008228	Lymphoma, Non-Hodgkin
D006689	Hodgkin Disease
D009101	Multiple Myeloma
D009190	Myelodysplastic Syndromes
D009196	Myeloproliferative Disorders

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007945	Leukemia, Lymphoid
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D001855	Bone Marrow Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D008223	Lymphoma
D054219	Neoplasms, Plasma Cell
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006474	Hemorrhagic Disorders

ID	Term
D016238	Cytapheresis
D001691	Biological Therapy
D013812	Therapeutics
D001781	Blood Component Removal
D047589	Leukocyte Reduction Procedures
D002469	Cell Separation
D003584	Cytological Techniques
D019411	Clinical Laboratory Techniques
D008919	Investigative Techniques

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	0	25	0	25	25	25
EG001	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	13	22	12	22	22	22