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

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The Washington University

Status and phase

Completed
Phase 2

Conditions

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

Treatments

Drug: BL-8040
Procedure: Hematopoietic cell transplant
Procedure: Leukapheresis

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT02639559
201602037

Details and patient eligibility

About

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.

Enrollment

50 patients

Sex

All

Ages

18 to 75 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

50 participants in 2 patient groups

Arm 1: Donors
Experimental 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.
Treatment:
Procedure: Leukapheresis
Drug: BL-8040
Arm 2: Recipients
Experimental group
Description:
-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
Treatment:
Procedure: Hematopoietic cell transplant

Trial documents
1

Trial contacts and locations

3

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Data sourced from clinicaltrials.gov

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