Plerixafor and Sargramostim (GM-CSF) for Mobilization of Allogeneic Sibling Donors
Condition: Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin; Hodgkin Disease; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma
MeSH terms: Leukemia; Multiple Myeloma; Hodgkin Disease; Lymphoma, Non-Hodgkin; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Myelodysplastic Syndromes
Intervention: Sargramostim; Plerixafor
Intervention MeSH terms: Plerixafor; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Summary:

      This study will gather information about the combination the drugs plerixafor with
      sargramostim in donors of blood-forming cells (stem cells). These stem cells will be
      collected from the donor and transplanted into their sibling. The investigators believe that
      the two drugs together will provide enough stem cells for transplantation and may also reduce
      the risk of graft versus host disease.
    

Eligibility criteria:

        Inclusion Criteria:

        Donor Eligibility

          -  Donor is 18 to 65 years of age inclusive.

          -  If female and of child-bearing age, donor must be non-pregnant, not breastfeeding, and
             agree to use adequate contraception.

          -  Donor is a 6/6 HLA-matched sibling willing to donate PBSC for transplant.

          -  Donor has adequate cardiac function with no history of congestive heart failure and no
             history of atrial fibrillation or ventricular tachyarrhythmia.

          -  Donor has adequate renal function as defined by a calculated serum creatinine
             clearance of ≥56 ml/min for females and ≥64 ml/min for males.

          -  Donor has adequate hepatic function as defined by a total bilirubin <2x normal or
             absence of hepatic fibrosis/cirrhosis.

          -  Donor has adequate neurologic function as defined by NO evidence of a severe central
             or peripheral neurologic abnormality. No history of cerebrovascular accident or
             seizure disorder requiring anticonvulsant medication.

          -  Donor must be HIV-1&2 antibody and HTLV-I&II 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.

          -  Donor must not have an active infection at the time of study entry.

          -  Donor does not have active alcohol or substance abuse within 6 months of study entry.

          -  Donor is not currently enrolled on another investigational agent study.

          -  Donor does not have any medical condition, which, in the opinion of the clinical
             investigator, would interfere with his/her evaluation.

          -  Ability of the donor to understand and the willingness to sign a written informed
             consent document.

        Recipient Eligibility

          -  Recipient must have available the successful collection of a GM-CSF + plerixafor
             mobilized product. When an adequate collection cannot be obtained, G-CSF will be used
             and some recipients may need to receive a combined product of mobilized cells with
             plerixafor + GM-CSF and G-CSF mobilized cells. Recipients who receive less than 2.0 X
             106 CD34+ cells/kg/actual recipient weight after six days of GM-CSF and two days of IV
             plerixafor will not be considered "eligible" but followed per protocol for safety
             purposes only.

          -  Recipient is 18 to 65 years of age inclusive.

          -  Recipient is willing and has a 6/6 HLA-matched sibling willing to donate PBSC for
             transplant.

          -  Recipient must provide signed informed consent.

          -  If female and of child-bearing age, recipient must be non-pregnant, not breastfeeding,
             and using adequate contraception.

          -  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.

               -  Myeloproliferative disorder or neoplasm

          -  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 renal function as defined by a serum creatinine clearance
             (Cockcroft-Gault equation)of ≥56 ml/min for females and ≥64 ml/min for males of normal

          -  Recipient must have adequate hepatic function as defined by a total bilirubin <2x
             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 have no evidence of active infection at the time of the transplant
             preparative regimen or at time of transplantation.

          -  Recipient must be HIV-1&2 antibody and HTLV-I & II antibody sero-negative, by FDA
             licensed test.

          -  Recipient has an ECOG performance status of 0 or 1.

          -  Recipient must demonstrate ability to be compliant with medical regimen.

          -  Recipient must not have active alcohol or substance abuse within 6 months of study
             entry.

          -  Recipient must not be enrolled on another investigational agent concurrently.

          -  Recipient must not have any medical condition, which, in the opinion of the clinical
             investigator, would interfere with the evaluation of the patient.

          -  Recipient must have a life expectancy of greater than 4 weeks.

          -  Both men and women and members of all races and ethnic groups are eligible for this
             trial.

        Exclusion Criteria:

        Donor Exclusion Criteria in addition to that stated above

          -  Donor may not be receiving any other investigational agents.

          -  Donor may not have a history of allergic reactions attributed to compounds of similar
             chemical or biologic composition to plerixafor or GM-CSF, or known hypersensitivity to
             yeast-derived products or any component of the product.