A Phase II Study Evaluating the Safety and Efficacy of Subcutaneous Plerixafor

A Phase II Study Evaluating the Safety and Efficacy of Subcutaneous Plerixafor for the Mobilization and Transplantation of HLA-Matched Sibling Donor Hematopoietic Stem Cells in Recipients With Hematological Malignancies

This is a Phase II, open-label, two strata, multicenter, prospective study of plerixafor-mobilized HLA-identical sibling allografts in recipients with hematological malignancies. This study will establish the safety and efficacy of subcutaneous plerixafor for this purpose.

The primary objective is to determine the proportion of donors whose cells can be successfully mobilized and collected with a sufficient CD34+ cell dose using plerixafor as the mobilizing agent, using an intention-to-treat analysis. Donor mobilization following plerixafor will be considered successful if ≥ 2.0x10e6 CD34+ cells/kg recipient weight are collected in no more than two leukapheresis collections.

All donors receiving plerixafor will be included in the analysis of the primary objective based on the intention-to-treat principle.Recipients will be classified into one of the two strata, myeloablative or reduced intensity, according to his/her conditioning regimen. The target enrollment is 64 donor/recipient pairs, 32 pairs per stratum.

Inclusion Criteria:

Donor:

• Donor eligibility will be determined according to applicable federal, state and local regulations and institutional standards
• 18-65 years of age
• 6/6 HLA-matched sibling
• Fulfill individual Transplant Center criteria to serve as a mobilized blood cell donor
• Serum creatinine <2.0mg/dl

Recipient:

• 18 to 65 years of age

• 6/6 HLA antigen matched sibling willing to donate PBSC for transplant

• Fulfill individual Transplant Center Criteria for transplant

• One of the following diagnoses:

  • Acute myelogenous leukemia (AML) in 1st remission or beyond with <5% marrow blasts and no circulating blasts. Marrow must be done within 30 days of the start of transplant conditioning regimen in alignment with other pre-transplant assessments.
  • Acute lymphoblastic leukemia (ALL) in 1st remission or beyond with <5% marrow blasts and no circulating blasts
  • Myelodysplastic syndrome, either intermediate-1,2, or high risk by International Prognostic Scoring System or transfusion dependent
  • Chronic myelogenous leukemia (CML) failing or intolerant to tyrosine kinase inhibitor based therapy
  • Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete remission, partial remission, or in relapse (but with at least stable disease after most recent therapy)
  • Chronic lymphocytic leukemia (CLL), relapsing after at least one prior regimen, or in remission with 17p deletion

• Serum creatinine must be <2.0mg/dl

• Total bilirubin and aspartate aminotransferase (AST) <3x normal

• Infectious disease marker (IDM) monitoring will be performed per institutional standards

• Karnofsky performance status of 70% or greater.

• Patients who have undergone a prior autologous transplantation are eligible for a reduced intensity transplant only

Exclusion Criteria:

Donor:

• Donor unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
• Donor already enrolled on another investigational agent study
• Pregnant or breast feeding females, or females not willing or able to use adequate contraception if sexually active

Recipient:

• Patient unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
• Patients with active, uncontrolled infection at the time of the transplant preparative regimen
• Pregnant or breast feeding females, or females not willing or able to use adequate contraception if sexually active
• Patients with a history of previous central nervous system (CNS) tumor involvement showing active symptoms or signs along with documented disease on lumbar puncture and MRI of the brain within 30 days of start of conditioning
• A condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of primary and secondary endpoints.