Phase 2
N=50
Safety and Efficacy of BL-8040 for the Mobilization of Donor Hematopoietic Stem Cells and Allogeneic Transplantation in Patients With Advanced Hematological Malignancies
Acute Myelogenous Leukemia · Acute Lymphoblastic Leukemia · Chronic Myelogenous Leukemia · Non-Hodgkin's Lymphoma · Non-Hodgkin Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT02639559 ↗Enrolled (actual)
50
Serious AEs
25.5%
Results posted
May 2019
Primary outcome: Primary: 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) — 22 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- BL-8040 (Drug); Leukapheresis (Procedure); Hematopoietic cell transplant (Procedure)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Washington University School of Medicine
- Primary completion
- Apr 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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) |
22 | — |
| SECONDARY Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only) |
17; 1; 2; 1; 1; 5 | — |
| SECONDARY Time to Neutrophil Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only) |
13 | — |
| SECONDARY Time to Platelet Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only) |
20 | — |
| SECONDARY Number of Recipients With Primary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) |
— | — |
| SECONDARY Incidence of Secondary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) |
— | — |
| SECONDARY Cumulative Incidence of Grade 2-4 Acute Graft Versus Host Disease (GvHD) as Measured by Minnesota Acute GVHD Criteria (Arm 2 Recipients Only) |
0.3636 | — |
| SECONDARY Cumulative Incidence of Chronic GvHD in Patients Who Have Undergone Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) |
0.5000 | — |
| SECONDARY 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) |
9 | — |
| SECONDARY Incidence of CMV Reactivation After Transplantation of Hematopoietic Cells Mobilized With BL-8040 in CMV Seropositive Recipients |
8 | — |
| SECONDARY Cumulative Incidence of Treatment-related Mortality After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) |
0.2273 | — |
| SECONDARY Cumulative Incidence of Disease Relapse/Progression After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) |
0.273 | — |
| SECONDARY Cumulative Incidence of Disease Relapse/Progression After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) |
0.273 | — |
| SECONDARY Kaplan-Meier Estimate of Event Free Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) |
34.1 | — |
| SECONDARY Kaplan-Meier Estimate of Event Free Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) |
34.1 | — |
| SECONDARY Kaplan-Meier Estimate of Overall Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) |
49.0 | — |
| SECONDARY Kaplan-Meier Estimate of Overall Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only) |
49.0 | — |
| SECONDARY Median Peripheral Blood CD34+ Cell Count (Arm 1 Donor Only) |
15 | — |
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.
Eligibility 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 o
Data sourced from ClinicalTrials.gov (NCT02639559). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.