Overview
Safety and Efficacy of BL-8040 for the Mobilization of Donor Hematopoietic Stem Cells and Allogeneic Transplantation in Patients With Advanced Hematological Malignancies
Status:
Active, not recruiting
Active, not recruiting
Trial end date:
2023-04-12
2023-04-12
Target enrollment:
0
0
Participant gender:
All
All
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.Phase:
Phase 2Accepts Healthy Volunteers?
Accepts Healthy VolunteersDetails
Lead Sponsor:
Washington University School of MedicineCollaborator:
BioLineRx, Ltd.
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.