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

Phase 2

Completed

• Conditions: Hodgkin Disease; Chronic Myelogenous Leukemia; Non-Hodgkin's Lymphoma; Non-Hodgkin Lymphoma; Multiple Myeloma; Acute Myelogenous Leukemia; Hodgkin's Disease; Myeloproliferative Neoplasm; Acute Lymphoblastic Leukemia; Hodgkins Disease
• Interventions: Drug: BL-8040; Procedure: Hematopoietic cell transplant; Procedure: Leukapheresis

• Registration Number: NCT02639559
• Lead Sponsor: Washington University School of Medicine

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-12-17
• Study First Submitted QC: 2015-12-21
• Study First Posted: 2015-12-24
• Study Start: 2016-03-31
• Primary Completion: 2018-04-12
• Results First Submitted: 2019-04-09
• Results First Submitted QC: 2019-04-09
• Results First Posted: 2019-05-01
• Study Completion: 2023-04-07
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-18
• Last Update Posted: 2023-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Donors	BL-8040	-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.
Arm 1: Donors	Leukapheresis	-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.
Arm 2: Recipients	Hematopoietic cell transplant	-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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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
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.
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.
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 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
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
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
Median Peripheral Blood CD34+ Cell Count (Arm 1 Donor Only)	At 3-4 hours after BL-8040
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 Disease Relapse/Progression After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)	At 2 years 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 Overall Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)	At 3 years post-transplantation	-The time from Day 0 to death
Kaplan-Meier Estimate of Event Free Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)	At 3 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.

Trial Locations

Locations (3)

Northside Hospital Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States