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Trial record 1 of 1 for:    NCT01158118
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Plerixafor and Sargramostim (GM-CSF) for Mobilization of Allogeneic Sibling Donors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01158118
First received: July 6, 2010
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Lymphoma, Non-Hodgkin
Hodgkin Disease
Leukemia, Lymphocytic, Chronic, B-Cell
Multiple Myeloma
Drug: Sargramostim
Drug: Plerixafor
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial Evaluating the Safety and Efficacy of Plerixafor and Sargramostim (GM-CSF) for the Mobilization of Peripheral Blood Stem Cells (PBSC) From Normal, HLA-Matched Allogeneic Sibling Donors

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Reduce the number of donors requiring a second collection [ Time Frame: 6 days (donor) ] [ Designated as safety issue: No ]
    The primary endpoint is to reduce the number of donors treated with GM-CSF who require a second collection to obtain a minimum CD34/Kg (2 x 106) necessary for allogeneic stem cell transplantation when compared to historic controls mobilized with GM-CSF or plerixafor alone. A reduction in failed first leukapheresis from 40% to less than 10% as seen with G-CSF alone would be considered clinically meaningful.


Secondary Outcome Measures:
  • Donor toxicity [ Time Frame: 30 days after completion of therapy ] [ Designated as safety issue: Yes ]
    To estimate the 95% confidence intervals of the proportion of HLA-identical sibling donors who experience grade 3-4 infusion toxicity.

  • Donor stem cell collection in 1 or 2 apheresis [ Time Frame: 6 days ] [ Designated as safety issue: Yes ]
    To estimate the 95% confidence intervals of the proportion of HLA-identical sibling donors who mobilize ≥ 2x106 CD34+ cells/Kg recipient weight safely following one or two aphereses and to estimate the 95% confidence intervals the proportion of HLA-identical sibling donors who reach 5x106 CD34+cells/Kg recipient weight in 1 or 2 aphereses.

  • Kinetics of stems cell, lymphocyte and dendritic cell mobilization [ Time Frame: Day 21 ] [ Designated as safety issue: Yes ]
    To determine the kinetics of stem cell, lymphocyte and dendritic cell mobilization using IV plerixafor and GM-CSF and to determine if peripheral blood stem cell products collected after mobilization with IV plerixafor can be used safely for hematopoietic cell transplantation in HLA-matched recipients as measured by neutrophil engraftment by day +21.

  • Pharmacokinetics and pharmacodynamics [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    Determine the pharmacokinetics and pharmacodynamics of GM-CSF on IV plerixafor.

  • Engraftment post transplant [ Time Frame: 100 days ] [ Designated as safety issue: No ]
    Determine the kinetics of immune reconstitution measured by engraftment of neutrophils, platelets, lymphocyte subsets, TREC analysis, and quantitative immunoglobulins after transplantation.

  • Rate of acute and chronic Graft vs. Host Disease (GvHD) [ Time Frame: 100 days ] [ Designated as safety issue: No ]
    Determine the rate of acute GvHD and chronic GvHD in recipients who receive GM-CSF + IV plerixafor mobilized peripheral blood stem cells.

  • Transplant related mortality [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    Determine transplant related mortality at day +100

  • Relapse, disease progression and death of any cause [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Determine relapse, disease progression and death of any cause


Enrollment: 48
Study Start Date: April 2011
Estimated Study Completion Date: January 2015
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 - Donor

Days 1-5: Mobilization with 5 mcg/kg/day GM-CSF

Day 5: Mobilization with 320 mcg/kg plerixafor IV

Day 5: Leukopheresis

If PBSC collected are not adequate, then donor will be mobilized with GM-CSF and plerixafor IV on day 6 and have leukopheresis collection on day 6.

Drug: Sargramostim
Other Name: GM-CSF, Leukine
Drug: Plerixafor
Other Name: AMD3100, Mozobil
No Intervention: Arm 2 - Recipient

Conditioning Regimens

  • fludarabine and busulfan +/- thymoglobulin
  • fractionated total body irradiation and cyclophosphamide
  • busulfan and cyclophosphamide
  • single dose total body irradiation and cyclophosphamide

Day -2 = GvHD prophylaxis

Day 0 or +1 = PBSC transplant

Day +7 until neutrophil engraftment = G-CSF 5 ug/kg/day


Detailed Description:

The main purpose of this study is to gather information about the combination the drugs plerixafor with sargramostim in donors of blood-forming cells (stem cells). Stem cells can be taken from the bone marrow of the pelvic bones or from the blood following treatment with drugs called growth factors; sargramostim is such a drug. Once stem cells leave the bone marrow and circulate in the blood, they are called peripheral blood stem cells (PBSCs). These cells can be collected through a routine procedure called apheresis, which involves placing two IVs into the arm which are connected to an apheresis machine; the machine then takes blood from the body, removes the stem cells, and returns the blood to the body.

Normally, a growth factor called filgrastim is given to donors in order to collect the stem cells used for transplantation. However, when stem cells collected using filgrastim are transplanted in patients, a possible unpredictable complication is graft versus host disease. It's thought that using a different growth factor such as sargramostim might reduce the occurrences of graft versus host disease in patients. However, sargramostim alone does not provide as many stem cells for transplantation as other growth factors. Plerixafor is another drug that can increase the number of PBSCs in a donor, but like with sargramostim, plerixafor alone does not always provide enough stem cells. This is why sargramostim and plerixafor are being combined in this study: 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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01158118

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Mark Schroeder, M.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01158118     History of Changes
Other Study ID Numbers: 10-1154 / 201108083
Study First Received: July 6, 2010
Last Updated: February 27, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Additional relevant MeSH terms:
Hodgkin Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Myelodysplastic Syndromes
Neoplasms, Plasma Cell
Preleukemia
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Precancerous Conditions
Vascular Diseases
JM 3100
Anti-HIV Agents

ClinicalTrials.gov processed this record on November 25, 2014