Safety and Efficacy of POL6326 for Mobilization/Transplant of Sibling Donor in Patients With Hematologic Malignancies

Inclusion Criteria:

Donor Inclusion Criteria

• Donor must be 18 to 70 years of age inclusive.
• Donor must be a 6/6 HLA-matched sibling willing to donate PBSC for transplant.
• Donor must have adequate cardiac function with no history of congestive heart failure and no history of atrial fibrillation or ventricular tachyarrhythmia.
• Donor must have adequate renal function as defined by a minimum creatinine clearance (CrCl) value of >30 ml/min. In the ongoing study of multiple myeloma patients, those treated with POL6326 who had a creatinine clearance of 35-58 ml/min showed no indication that this mild to moderate renal impairment had an impact on safety.
• Donor must have adequate hepatic function as defined by a total bilirubin <3x upper limit of normal.
• Donor must have adequate neurologic function as defined by NO evidence of a severe central or peripheral neurologic abnormality and no history of cerebrovascular accident or seizure disorder requiring anticonvulsant medication.
• Donor must be HIV-1&2 antibody and HTLV-1&2 antibody sero-negative by FDA licensed test.
• Donor must have an ECOG performance status of 0 or 1.
• Donor must demonstrate ability to be compliant with study regimen.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Donor must be able to understand and willing to sign an IRB approved written informed consent document.

Recipient Inclusion Criteria

• Recipient must have available the successful collection of a POL62326 mobilized product. When an adequate collection (2.0 X 10^6 CD34+ cells/kg/actual recipient weight) cannot be obtained using two days of IV POL6326, the mobilization will be considered unsuccessful and G-CSF will be administered per standard institutional procedures. Some recipients may need to receive a combined product of cells mobilized with POL6326 and G-CSF. These recipients will not be considered "eligible" but will be followed per protocol for safety purposes only.
• Recipient must be 18 to 65 years of age inclusive.
• Recipient must have a 6/6 HLA-matched sibling willing to donate PBSC for transplant.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

• Recipient must have one of the following diagnoses:

  • Acute myelogenous leukemia (AML) in 1st or subsequent remission or in relapse,
  • Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission or in relapse,
  • Myelodysplastic syndrome either intermediate 1 or 2, or high risk by the International Prognostic Scoring System,
  • Chronic myelogenous leukemia (CML) in accelerated or second chronic phase,
  • Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete remission, partial remission, or refractory relapse,
  • Chronic lymphocytic leukemia (CLL), Rai Stage 2-4, failing at least 2 prior regimens, OR
  • Multiple myeloma (MM), Stage 2-3.
• Recipient must have adequate cardiac function with a left ventricular ejection fraction > 40%.
• Recipient must have 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.
• Recipient must have adequate hepatic function as defined by a total bilirubin <3x upper limit of normal or absence of hepatic fibrosis/cirrhosis.
• Recipient must have adequate neurologic function as defined by NO evidence of a severe central or peripheral neurologic abnormality. Patients with a history of previous CNS tumor involvement are eligible provided they are without symptoms or signs and the CNS is now free of disease on lumbar puncture and CT scan of the brain.
• Recipient must be HIV-1&2 antibody and HTLV-1&2 antibody sero-negative by FDA licensed test.
• Recipient must have an ECOG performance status of 0 or 1.
• Recipient must demonstrate ability to be compliant with medical regimen.
• Recipient must have life expectancy of greater than 2 months.
• Recipient must be able to understand and willing to sign an IRB approved written informed consent document.

Exclusion Criteria:

Donor Exclusion Criteria

• Donor must not have an active infection at the time of study entry.
• Donor must not have active alcohol or substance abuse within 6 months of study entry.
• Donor must not be currently enrolled on another investigational agent study.
• Donor must not have any medical condition, which, in the opinion of the clinical investigator, would interfere with his/her evaluation.
• Donor must not have an 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.
• If female and of child-bearing age, donor must not be pregnant or breastfeeding.

Recipient Exclusion Criteria

• Recipient must not have had (the following therapies within the following timeframe):

  • Previous allogeneic transplant
  • Previous treatment with plerixafor
  • Investigative drugs within 21 days
• Recipient must have no evidence of active infection at the time of the transplant preparative regimen or at time of transplantation.
• Recipient must have no active alcohol or substance abuse within 6 months of study entry.
• Recipient must not have a history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
• Recipients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Recipient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to POL6326 or other agents used in the study.
• Recipient must not be pregnant and/or breastfeeding.
• Recipient must not have any medical condition which, in the opinion of the clinical investigator, would interfere with the evaluation of the patient.