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

NCT02639559 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 201602037
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

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.

Conditions

Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Non-Hodgkin's Lymphoma; Non-Hodgkin Lymphoma; Hodgkin Disease; Hodgkin's Disease; Multiple Myeloma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm

Outcome Measures

Primary Outcomes (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 Outcomes (17)

• 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

• Time to Neutrophil Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only)

  Up to Day 28

• Time to Platelet Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only)

  Through 90 days

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

  Up to 1 year after transplantation

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

  Up to 1 year after transplantation

Study Arms (2)

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

Interventions

BL-8040 DRUG

Arm 1: Donors

Leukapheresis PROCEDURE

Arm 1: Donors

Hematopoietic cell transplant PROCEDURE

Arm 2: Recipients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age 18 to 75 years

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• BioLineRx, Ltd.: collaborator

Study Sites (3)

Northside Hospital Cancer Institute

Atlanta, Georgia, 30342, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, Non-Hodgkin; Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndromes; Myeloproliferative Disorders

Interventions

4-fluorobenzoyl-TN-14003; Leukapheresis

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Results Point of Contact

• Title: Geoffrey Uy, M.D.
• Organization: Washington University School of Medicine

guy@wustl.edu

314-454-8304

Study Officials

• Geoffrey Uy, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2015
• First Posted: December 24, 2015
• Study Start: March 31, 2016
• Primary Completion: April 12, 2018
• Study Completion: April 7, 2023
• Last Updated: November 7, 2023
• Results First Posted: May 1, 2019

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)