Clinical trial NCT02639559: Safety and Efficacy of BL-8040 for the Mobilization of Donor Hematopoietic Stem Cells and Allogeneic Transplantation in Patients With Advanced Hematological Malignancies
Official title: A Phase II Study Evaluating the Safety and Efficacy of BL-8040 for the Mobilization of Donor Hematopoietic Stem Cells and Allogeneic Transplantation in Patients With Advanced Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Chronic Myelogenous Leukemia
Non-Hodgkin's Lymphoma
Non-Hodgkin Lymphoma
Hodgkin Disease
Hodgkins Disease
Hodgkin's Disease
Multiple Myeloma
Myelodysplastic Syndrome
Myeloproliferative Neoplasm
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: BioLineRx, Ltd.
First posted: 2015-12-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 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.

Primary outcomes:
measure: 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)
timeFrame: Up to Day 2
Secondary outcomes:
measure: Safety and Tolerability of BL-8040 in Healthy Donors as Measured by Number and Grade of Adverse Events (Arm 1 Donors Only)
timeFrame: Up to 5 years
measure: Time to Neutrophil Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only)
timeFrame: Up to Day 28
measure: Time to Platelet Engraftment Post-transplant in Patients Undergoing Allogeneic Stem Cell Transplant (Arm 2 Recipients Only)
timeFrame: Through 90 days
measure: Number of Recipients With Primary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
timeFrame: Up to 1 year after transplantation
measure: Incidence of Secondary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
timeFrame: Up to 1 year after transplantation
measure: Cumulative Incidence of Grade 2-4 Acute Graft Versus Host Disease (GvHD) as Measured by Minnesota Acute GVHD Criteria (Arm 2 Recipients Only)
timeFrame: Day 100
measure: Cumulative Incidence of Chronic GvHD in Patients Who Have Undergone Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
timeFrame: From Day 100 through 1 year after transplantation
measure: 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)
timeFrame: Up to Day 2
measure: Incidence of CMV Reactivation After Transplantation of Hematopoietic Cells Mobilized With BL-8040 in CMV Seropositive Recipients
timeFrame: Up to 1 year after transplantation
measure: Cumulative Incidence of Treatment-related Mortality After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
timeFrame: Up to 1 year after transplantation
measure: Cumulative Incidence of Disease Relapse/Progression After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
timeFrame: At 1 year post-tranplantation
measure: Cumulative Incidence of Disease Relapse/Progression After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
timeFrame: At 2 years post-tranplantation
measure: Kaplan-Meier Estimate of Event Free Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
timeFrame: At 2 years post-transplantation
measure: Kaplan-Meier Estimate of Event Free Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
timeFrame: At 3 years post-transplantation
measure: Kaplan-Meier Estimate of Overall Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
timeFrame: At 2 years post-transplantation
measure: Kaplan-Meier Estimate of Overall Survival After Transplantation of Hematopoietic Cells Mobilized With BL-8040 (Arm 2 Recipients Only)
timeFrame: At 3 years post-transplantation
measure: Median Peripheral Blood CD34+ Cell Count (Arm 1 Donor Only)
timeFrame: At 3-4 hours after BL-8040
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Northside Hospital Cancer Institute
state: Georgia
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Washington University School of Medicine
name: Geoffrey Uy, M.D.
role: PRINCIPAL_INVESTIGATOR
References: