Safety and Efficacy of BL-8040 for the Mobilization of Donor Hematopoietic Stem Cells and Allogeneic Transplantation in Patients With Advanced Hematological Malignancies

Sponsor
Washington University School of Medicine (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02639559
Collaborator
BioLineRx, Ltd. (Industry)
50
Enrollment
3
Locations
2
Arms
84.4
Anticipated Duration (Months)
16.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
50 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study Evaluating the Safety and Efficacy of BL-8040 for the Mobilization of Donor Hematopoietic Stem Cells and Allogeneic Transplantation in Patients With Advanced Hematological Malignancies
Actual Study Start Date :
Mar 31, 2016
Actual Primary Completion Date :
Apr 12, 2018
Anticipated Study Completion Date :
Apr 12, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: 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.

Drug: BL-8040

Procedure: Leukapheresis

Experimental: 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

Procedure: Hematopoietic cell transplant

Outcome Measures

Primary Outcome Measures

  1. 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 Outcome Measures

  1. 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

  2. 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.

  3. 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.

  4. 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]

  5. Incidence of Secondary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) [Up to 1 year after transplantation]

  6. 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.

  7. 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.

  8. 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]

  9. 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

  10. 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

  11. Incidence of Disease Relapse/Progression After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) [Up to 3 years after transplantation]

    -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

  12. Probability of Event Free Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) [Up to 3 years after 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.

  13. Probability of Overall Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) [Up to 3 years after transplantation]

    -The time from Day 0 to death

  14. Median Peripheral Blood CD34+ Cell Count (Arm 1 Donor Only) [At 3-4 hours after BL-8040]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts 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.

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.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Northside Hospital Cancer InstituteAtlantaGeorgiaUnited States30342
2Washington University School of MedicineSaint LouisMissouriUnited States63110
3Ohio State UniversityColumbusOhioUnited States43210

Sponsors and Collaborators

  • Washington University School of Medicine
  • BioLineRx, Ltd.

Investigators

  • Principal Investigator: Geoffrey Uy, M.D., Washington University School of Medicine

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT02639559
Other Study ID Numbers:
  • 201602037
First Posted:
Dec 24, 2015
Last Update Posted:
Apr 8, 2021
Last Verified:
Apr 1, 2021
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:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group TitleArm 1: DonorsArm 2: Recipients
Arm/Group Description-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.-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
Period Title: Overall Study
STARTED2525
COMPLETED2422
NOT COMPLETED13

Baseline Characteristics

Arm/Group TitleArm 1: DonorsArm 2: RecipientsTotal
Arm/Group Description-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.-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 0Total of all reporting groups
Overall Participants252550
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
55
58
55
Sex: Female, Male (Count of Participants)
Female
7
28%
10
40%
17
34%
Male
18
72%
15
60%
33
66%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
2
8%
2
8%
4
8%
Not Hispanic or Latino
21
84%
23
92%
44
88%
Unknown or Not Reported
2
8%
0
0%
2
4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
0
0%
0
0%
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
1
4%
1
4%
2
4%
White
20
80%
22
88%
42
84%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
4
16%
2
8%
6
12%
Region of Enrollment (participants) [Number]
United States
25
100%
25
100%
50
100%

Outcome Measures

1. Primary Outcome
TitleNumber 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)
Description
Time FrameUp to Day 2

Outcome Measure Data

Analysis Population Description
This outcome measure is for Arm 1 - Donors only.
Arm/Group TitleArm 1: DonorsArm 2: Recipients
Arm/Group Description-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.-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
Measure Participants240
Count of Participants [Participants]
22
88%
2. Secondary Outcome
TitleSafety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only)
Description-Adverse events will be graded according to the NCI CTCAE version 4.03
Time FrameUp to 5 years

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
3. Secondary Outcome
TitleTime to Neutrophil Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only)
Description-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 FrameUp to Day 28

Outcome Measure Data

Analysis Population Description
-Donors are not evaluable for this outcome measure.
Arm/Group TitleArm 1: DonorsArm 2: Recipients
Arm/Group Description-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.-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
Measure Participants022
Median (Full Range) [days]
13
4. Secondary Outcome
TitleTime to Platelet Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only)
Description-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 FrameThrough 90 days

Outcome Measure Data

Analysis Population Description
-Donors are not evaluable for this outcome measure. 1 recipient was not evaluable due to now platelet nadir and 1 recipient was not evaluable due to no engraftment.
Arm/Group TitleArm 1: DonorsArm 2: Recipients
Arm/Group Description-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.-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
Measure Participants020
Median (Full Range) [days]
20
5. Secondary Outcome
TitleNumber of Recipients With Primary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
Description
Time FrameUp to 1 year after transplantation

Outcome Measure Data

Analysis Population Description
-Donors are not evaluable for this outcome measure.
Arm/Group TitleArm 1: DonorsArm 2: Recipients
Arm/Group Description-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.-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
Measure Participants022
Count of Participants [Participants]
0
0%
6. Secondary Outcome
TitleIncidence of Secondary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
Description
Time FrameUp to 1 year after transplantation

Outcome Measure Data

Analysis Population Description
-Donors are not evaluable for this outcome measure.
Arm/Group TitleArm 1: DonorsArm 2: Recipients
Arm/Group Description-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.-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
Measure Participants022
Count of Participants [Participants]
0
0%
7. Secondary Outcome
TitleCumulative Incidence of Grade 2-4 Acute Graft Versus Host Disease (GvHD) as Measured by Minnesota Acute GVHD Criteria (Arm 2 Recipients Only)
DescriptionAcute 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 FrameDay 100

Outcome Measure Data

Analysis Population Description
-Donors are not evaluable for this outcome measure.
Arm/Group TitleArm 1: DonorsArm 2: Recipients
Arm/Group Description-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.-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
Measure Participants022
Number (95% Confidence Interval) [proportion of participants]
0.3636
1.5%
8. Secondary Outcome
TitleCumulative Incidence of Chronic GvHD in Patients Who Have Undergone Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
DescriptionChronic 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 FrameFrom Day 100 through 1 year after transplantation

Outcome Measure Data

Analysis Population Description
-Donors are not evaluable for this outcome measure.
Arm/Group TitleArm 1: DonorsArm 2: Recipients
Arm/Group Description-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.-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
Measure Participants022
Number (95% Confidence Interval) [proportion of participants]
0.5000
2%
9. Secondary Outcome
TitleNumber 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)
Description
Time FrameUp to Day 2

Outcome Measure Data

Analysis Population Description
-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/Group TitleArm 1: DonorsArm 2: Recipients
Arm/Group Description-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.-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
Measure Participants90
Count of Participants [Participants]
9
36%
10. Secondary Outcome
TitleIncidence of CMV Reactivation After Transplantation of Hematopoietic Cells Mobilized With BL-8040 in CMV Seropositive Recipients
Description-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 FrameUp to 1 year after transplantation

Outcome Measure Data

Analysis Population Description
-Donors are not evaluable for this outcome measure.
Arm/Group TitleArm 1: DonorsArm 2: Recipients
Arm/Group Description-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.-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
Measure Participants022
Count of Participants [Participants]
8
32%
11. Secondary Outcome
TitleCumulative Incidence of Treatment-related Mortality After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
Description-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 FrameUp to 1 year after transplantation

Outcome Measure Data

Analysis Population Description
-Donors are not evaluable for this outcome measure.
Arm/Group TitleArm 1: DonorsArm 2: Recipients
Arm/Group Description-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.-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
Measure Participants022
Number (95% Confidence Interval) [proportion of participants]
0.2273
0.9%
12. Secondary Outcome
TitleIncidence of Disease Relapse/Progression After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
Description-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 FrameUp to 3 years after transplantation

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
13. Secondary Outcome
TitleProbability of Event Free Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
Description-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 FrameUp to 3 years after transplantation

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
14. Secondary Outcome
TitleProbability of Overall Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
Description-The time from Day 0 to death
Time FrameUp to 3 years after transplantation

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
15. Secondary Outcome
TitleMedian Peripheral Blood CD34+ Cell Count (Arm 1 Donor Only)
Description
Time FrameAt 3-4 hours after BL-8040

Outcome Measure Data

Analysis Population Description
Recipients are not evaluable for this outcome measure.
Arm/Group TitleArm 1: DonorsArm 2: Recipients
Arm/Group Description-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.-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
Measure Participants250
Median (Full Range) [CD34/microliters]
15

Adverse Events

Time Frame-Adverse events for donors were collected from the date the participant signed the consent form through 30 days after the last dose of BL-8040. In addition, any adverse events at least possibly related to BL-8040 that occurs up to 5 years after the BL-8040 dose should be recorded. -Adverse events for recipients were collected from the start of the conditioning regimen until Day +100 post transplant. Only grade 3-5 non-hematologic adverse events will be collected.
Adverse Event Reporting Description
Arm/Group TitleArm 1: DonorsArm 2: Recipients
Arm/Group Description-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.-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
All Cause Mortality
Arm 1: DonorsArm 2: Recipients
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/25 (0%) 11/22 (50%)
Serious Adverse Events
Arm 1: DonorsArm 2: Recipients
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/25 (0%) 12/22 (54.5%)
Blood and lymphatic system disorders
Febrile neutropenia0/25 (0%) 2/22 (9.1%)
Gastrointestinal disorders
Diarrhea0/25 (0%) 3/22 (13.6%)
Mucositis oral0/25 (0%) 1/22 (4.5%)
Nausea0/25 (0%) 1/22 (4.5%)
Vomiting0/25 (0%) 1/22 (4.5%)
General disorders
Fever0/25 (0%) 1/22 (4.5%)
Generalized weakness0/25 (0%) 1/22 (4.5%)
Infections and infestations
Sepsis0/25 (0%) 2/22 (9.1%)
Upper respiratory infection0/25 (0%) 1/22 (4.5%)
Injury, poisoning and procedural complications
Fall0/25 (0%) 1/22 (4.5%)
Nervous system disorders
Headache0/25 (0%) 1/22 (4.5%)
Psychiatric disorders
Delirium0/25 (0%) 1/22 (4.5%)
Renal and urinary disorders
Acute kidney injury0/25 (0%) 3/22 (13.6%)
Reproductive system and breast disorders
Genital edema0/25 (0%) 1/22 (4.5%)
Testicular pain0/25 (0%) 1/22 (4.5%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure0/25 (0%) 1/22 (4.5%)
Other (Not Including Serious) Adverse Events
Arm 1: DonorsArm 2: Recipients
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total25/25 (100%) 22/22 (100%)
Blood and lymphatic system disorders
Anemia17/25 (68%) 0/22 (0%)
Febrile neutropenia0/25 (0%) 7/22 (31.8%)
Cardiac disorders
Acute systolic heart failure0/25 (0%) 1/22 (4.5%)
Atrial fibrillation1/25 (4%) 0/22 (0%)
Chest pain-cardiac0/25 (0%) 1/22 (4.5%)
Sinus brachycardia4/25 (16%) 0/22 (0%)
Sinus tachycardia2/25 (8%) 0/22 (0%)
Eye disorders
Eye pain1/25 (4%) 0/22 (0%)
Watering eyes1/25 (4%) 0/22 (0%)
Gastrointestinal disorders
Abdominal pain0/25 (0%) 1/22 (4.5%)
Colitis0/25 (0%) 1/22 (4.5%)
Diarrhea0/25 (0%) 1/22 (4.5%)
Esophagitis0/25 (0%) 1/22 (4.5%)
Gastrointestinal reflux disease1/25 (4%) 0/22 (0%)
Mucositis oral0/25 (0%) 7/22 (31.8%)
Nausea1/25 (4%) 2/22 (9.1%)
Oral dysesthesia6/25 (24%) 0/22 (0%)
Toothache1/25 (4%) 0/22 (0%)
Vomiting2/25 (8%) 0/22 (0%)
General disorders
Chills1/25 (4%) 0/22 (0%)
Edema limbs-anasarca0/25 (0%) 1/22 (4.5%)
Fatigue3/25 (12%) 2/22 (9.1%)
Fever1/25 (4%) 0/22 (0%)
Infusion related reaction1/25 (4%) 0/22 (0%)
Injection site reaction20/25 (80%) 0/22 (0%)
Localized edema1/25 (4%) 0/22 (0%)
Pain1/25 (4%) 0/22 (0%)
Vibration sensation1/25 (4%) 0/22 (0%)
Hepatobiliary disorders
Hepatic failure0/25 (0%) 1/22 (4.5%)
Immune system disorders
Allergic reaction20/25 (80%) 0/22 (0%)
Infections and infestations
Bacteremia-Klebsiella pneumoniae0/25 (0%) 1/22 (4.5%)
Bacteremia-VRE0/25 (0%) 1/22 (4.5%)
Catheter related infection0/25 (0%) 1/22 (4.5%)
Clostridium difficile0/25 (0%) 2/22 (9.1%)
Hepatitis B Core Ab positive2/25 (8%) 0/22 (0%)
Lung infection0/25 (0%) 2/22 (9.1%)
Mild head cold1/25 (4%) 0/22 (0%)
Oral thrush0/25 (0%) 1/22 (4.5%)
Papulopustular rash1/25 (4%) 0/22 (0%)
Skin infection0/25 (0%) 1/22 (4.5%)
Urinary tract infection0/25 (0%) 2/22 (9.1%)
Injury, poisoning and procedural complications
Bruising1/25 (4%) 0/22 (0%)
Investigations
Activated partial thromboplastin time prolonged1/25 (4%) 0/22 (0%)
Alanine aminotransferase increased1/25 (4%) 2/22 (9.1%)
Alkaline phosphatase increased1/25 (4%) 0/22 (0%)
Aspartate aminotransferase increased0/25 (0%) 1/22 (4.5%)
Blood bilirubin increased0/25 (0%) 1/22 (4.5%)
Cholesterol high6/25 (24%) 0/22 (0%)
GGT increased0/25 (0%) 1/22 (4.5%)
Hemoglobin increased2/25 (8%) 0/22 (0%)
Lymphocyte count decreased8/25 (32%) 0/22 (0%)
Lymphocyte count increased22/25 (88%) 0/22 (0%)
Neutrophil count decreased1/25 (4%) 0/22 (0%)
Platelet count decreased22/25 (88%) 0/22 (0%)
White blood cell decreased2/25 (8%) 0/22 (0%)
Metabolism and nutrition disorders
Anorexia0/25 (0%) 1/22 (4.5%)
Dehydration0/25 (0%) 1/22 (4.5%)
Hypercalcemia0/25 (0%) 1/22 (4.5%)
Hyperglycemia3/25 (12%) 4/22 (18.2%)
Hyperkalemia1/25 (4%) 2/22 (9.1%)
Hypermagnesemia0/25 (0%) 1/22 (4.5%)
Hypertriglyceridemia4/25 (16%) 0/22 (0%)
Hyperuricemia1/25 (4%) 2/22 (9.1%)
Hypocalcemia10/25 (40%) 0/22 (0%)
Hypokalemia0/25 (0%) 4/22 (18.2%)
Hypomagnesemia1/25 (4%) 0/22 (0%)
Hyponatremia1/25 (4%) 1/22 (4.5%)
Hypophosphatemia0/25 (0%) 6/22 (27.3%)
Type II diabetes1/25 (4%) 0/22 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia1/25 (4%) 0/22 (0%)
Back pain0/25 (0%) 2/22 (9.1%)
Bone pain2/25 (8%) 0/22 (0%)
Foot pain1/25 (4%) 0/22 (0%)
Leg/knee pain1/25 (4%) 0/22 (0%)
Pain in extremity1/25 (4%) 0/22 (0%)
Nervous system disorders
Dizziness1/25 (4%) 0/22 (0%)
Dysesthesia1/25 (4%) 0/22 (0%)
Dysgeusia1/25 (4%) 0/22 (0%)
Headache3/25 (12%) 3/22 (13.6%)
Paresthesia3/25 (12%) 0/22 (0%)
Syncope1/25 (4%) 1/22 (4.5%)
Psychiatric disorders
Anxiety1/25 (4%) 0/22 (0%)
Insomnia2/25 (8%) 0/22 (0%)
Renal and urinary disorders
Cystitis noninfective0/25 (0%) 1/22 (4.5%)
Renal failure0/25 (0%) 1/22 (4.5%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis2/25 (8%) 0/22 (0%)
Dyspnea1/25 (4%) 0/22 (0%)
Epistaxis0/25 (0%) 1/22 (4.5%)
Hypoxia0/25 (0%) 4/22 (18.2%)
Pneumonitis0/25 (0%) 1/22 (4.5%)
Pulmonary edema0/25 (0%) 1/22 (4.5%)
Respiratory failure0/25 (0%) 1/22 (4.5%)
Sore throat0/25 (0%) 1/22 (4.5%)
Skin and subcutaneous tissue disorders
Rash maculo-papular1/25 (4%) 0/22 (0%)
Scrotal pruritus0/25 (0%) 1/22 (4.5%)
Vascular disorders
Hypertension16/25 (64%) 11/22 (50%)
Hypotension2/25 (8%) 1/22 (4.5%)
Veno-occlusive disease0/25 (0%) 1/22 (4.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/TitleGeoffrey Uy, M.D.
OrganizationWashington University School of Medicine
Phone314-454-8304
Emailguy@wustl.edu
Responsible Party:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT02639559
Other Study ID Numbers:
  • 201602037
First Posted:
Dec 24, 2015
Last Update Posted:
Apr 8, 2021
Last Verified:
Apr 1, 2021