Safety and Efficacy of BL-8040 for the Mobilization of Donor Hematopoietic Stem Cells and Allogeneic Transplantation in Patients With Advanced Hematological Malignancies
Condition: 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
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Hematologic Neoplasms; Hodgkin Disease; Myelodysplastic Syndromes; Myeloproliferative Disorders
Intervention: BL-8040; Leukapheresis; Hematopoietic cell transplant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

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.