safety and efficacy of bl-8040 for the mobilization of donor hematopoietic stem cells and allogeneic transplantation in patients with advanced hematological malignancies

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

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.