Intravenous (IV) AMD3100 for Mobilization and Matched Related Transplant for Advanced Hematological Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00914849
First received: June 1, 2009
Last updated: July 14, 2016
Last verified: July 2016

June 1, 2009
July 14, 2016
August 2009
January 2011   (final data collection date for primary outcome measure)
Number of Donors Treated With IV AMD3100 Who Required a Second Collection to Obtain the Minimum CD34/kg (2 X 106) Necessary for Allogeneic Stem Cell Transplant [ Time Frame: Completion of enrollment of all donors (17 months) ] [ Designated as safety issue: Yes ]
To reduce the number of donors treated with IV AMD3100 who require a second collection to obtain the minimum CD34/kg (2 X 106) necessary for allogeneic stem cell transplant when compared to our historic group who received 240ug SC AMD3100. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00914849 on ClinicalTrials.gov Archive Site
  • Number of Donors Who Experience Grade 3-4 Infusional Toxicity [ Time Frame: Up to Day 2 ] [ Designated as safety issue: Yes ]
  • Number of Recipients Who Have Neutrophil Engraftment [ Time Frame: Day 21 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of IV AMD3100 as Measured by the Mean Maximum Plasma Concentration (Cmax) [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]
  • Pharmacokinetics of IV AMD3100 as Measured by Half Life [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]
  • Pharmacodynamics of IV AMD3100 on Stem Cell and T-cell Phenotyping and on Immune Reconstitution After Transplantation. [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]
  • Rate of Acute GVHD (Grade II-IV) in Recipients [ Time Frame: Day 0-Day 100 (acute) ] [ Designated as safety issue: Yes ]
  • Rate of Acute GVHD (Grade III-IV) in Recipients [ Time Frame: Day 0-Day 100 (acute) ] [ Designated as safety issue: Yes ]
  • Time to Neutrophil Engraftment for Recipients [ Time Frame: Up through Day 100 ] [ Designated as safety issue: No ]
    Measured by determine the first 3 consecutive measurement of neutrophil count = 500/ul following conditioning regimen induced nadir.
  • Time to Platelet Engraftment for Recipients [ Time Frame: Up to Day 100 ] [ Designated as safety issue: No ]
    Measured by determining the first of 3 consecutive measurements of platelet count = 20,000/ul without platelet transfusion support for 7 days.
  • Transplant Related Mortality Rate for Recipients [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    Death that results from a transplant procedure related complication rather than from relapse of the underlying disease or unrelated cause.
  • Grade 3-4 Toxicity for Recipients [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Assessed and graded according to NCI Common Terminology for Adverse Events Version 3.0.
  • Rate of Chronic GVHD in Recipients [ Time Frame: Day 101-1 year ] [ Designated as safety issue: Yes ]
  • Number of Donors Who Experience Grade 3-4 Mobilization Toxicity Due to Pheresis Procedure [ Time Frame: Up to Day 2 ] [ Designated as safety issue: No ]
  • To estimate with 95% confidence intervals the proportion of donors who experience grade 3-4 infusional toxicity & the proportion from whom ≥ 2.0 x 10e6 CD34+ cells/kg recipient weight are safely mobilized following 1 or 2 intravenous infusions. [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • To determine the kinetics of mobilization using IV AMD3100 and to determine if stem cell products collected after mobilization with IV AMD3100 can be used safely for transplant in HLA-matched recipients as measured by neutrophil engraftment by day +21. [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • To determine the pharmacokinetics and pharmacodynamics of IV AMD3100 on stem cell and T-cell phenotyping and on immune reconstitution after transplantation. [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • To determine the rate of acute GVHD and chronic GVHD in patients who receive IV AMD3100 mobilized peripheral blood stem cells. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Intravenous (IV) AMD3100 for Mobilization and Matched Related Transplant for Advanced Hematological Malignancies
A Phase II Study Evaluating the Safety and Efficacy of Intravenous AMD3100 for the Mobilization and Transplantation of HLA-Matched Sibling Donor Hematopoietic Stem Cells in Patients With Advanced Hematological Malignancies
To reduce the number of donors treated with IV AMD3100 who require a second collection to obtain the minimum cells necessary for allogeneic stem cell transplant.
  • To reduce the number of donors treated with intravenous (IV) AMD3100 who require a second collection to obtain the minimum CD34/kg (2 X 106) necessary for allogeneic stem cell transplantation when compared to our historic group who received 240ug SC AMD3100 from 33% (8 in 24) to 11% (3 in 27).
  • To estimate with 95% confidence intervals the proportion of human leukocyte antigen (HLA)-identical sibling donors who experience grade 3-4 infusional toxicity and the proportion from whom ≥ 2.0 x 10e6 CD34+ cells/kg recipient weight are safely mobilized following one or two intravenous infusions.
  • To determine the kinetics of stem cell and lymphocyte mobilization using IV AMD3100 and to determine if peripheral blood stem cell products collected after mobilization with IV AMD3100 can be used safely for hematopoietic cell transplantation in HLA-matched recipients as measured by neutrophil engraftment by day +21.
  • To determine the pharmacokinetics and pharmacodynamics of IV AMD3100 on stem cell and T-cell phenotyping and on immune reconstitution after transplantation.
  • To determine the rate of acute graft-versus-host disease (GVHD) and chronic GVHD in patients who receive IV AMD3100 mobilized peripheral blood stem cells.
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Hematologic Neoplasms
  • Drug: AMD3100
    Other Names:
    • Mozobil
    • Plerixafor
  • Procedure: Leukopheresis
  • Procedure: Stem cell transplant
  • Experimental: Arm 1 - Donor
    • Day 1

      • AMD3100 320 ug/kg IV
      • Leukopheresis
    • Day 2 (if peripheral blood stem cell (PBSC) collected is not sufficient)

      • AMD3100 320 ug/kg IV
      • Leukopheresis
    Interventions:
    • Drug: AMD3100
    • Procedure: Leukopheresis
  • Experimental: Arm 2 - Recipient

    Standard of care and physician choice myeloablative or non-myeloablative chemotherapy with or without total body irradiation (permitted = cyclophosphamide and single dose total body irradiation (TBI) / fludarabine and busulfan / fractionated TBI and cyclophosphamide / fractionated TBI, etoposide, and cyclophosphamide / busulfan and cyclophosphamide / fludarabine, busulfan, and ATGAM

    Day 0 = Stem Cell Transplant

    Intervention: Procedure: Stem cell transplant

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
68
February 2012
January 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

Donor Eligibility

  • Donor is 18 to 70 years of age inclusive.
  • If female and of child-bearing age: must be non-pregnant, not breast feeding and agree to use adequate contraception.
  • Donor is a 6/6 HLA-matched sibling willing to donate PBSC for transplant.
  • Donor must be willing to provide written informed consent.
  • Adequate cardiac function with no history of congestive heart failure and no history of atrial fibrillation or ventricular tachyarrhythmia.
  • Adequate renal function as defined by a calculated serum creatinine clearance of ≥75% of normal (Cockcroft-Gault equation).
  • Adequate hepatic function as defined by a total bilirubin <2x normal or absence of hepatic fibrosis/cirrhosis.
  • 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 Food and Drug Administration (FDA) licensed test.
  • Donor must have an Eastern Cooperative Oncology Group (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.

Recipient Eligibility

  • Recipient must have available the successful collection of an AMD3100 mobilized product. When an adequate collection cannot be obtained using G-CSF, some recipients may need to receive a combined product of mobilized cells with AMD3100 and g granulocyte-colony stimulating factor (G-CSF). Recipients who receive less than 2.0 X 106 CD34+ cells/kg/actual recipient weight after two days of IV AMD3100 will not be considered "eligible" but followed per protocol for safety purposes only.
  • Patient is 18 to 65 years of age inclusive.
  • Patient is willing and has a 6/6 HLA-matched sibling willing to donate PBSC for transplant.
  • Patient must provide signed informed consent.
  • If female and of child-bearing age: must be non-pregnant, not breast feeding, and uses adequate contraception.
  • Patient 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.
  • 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.
  • Adequate renal function as defined by a serum creatinine clearance of ≥75% of normal (Cockcroft-Gault equation).
  • Adequate hepatic function as defined by a total bilirubin <2x normal or absence of hepatic fibrosis/cirrhosis.
  • Adequate neurologic function as defined by NO evidence of a severe central or peripheral neurologic abnormality. Patients with a history of previous central nervous system (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.
  • No evidence of active infection at the time of the transplant preparative regimen or at time of transplantation.
  • Patient must be HIV-1&2 antibody and HTLV-I & II antibody sero-negative, by FDA licensed test.
  • Patient has an ECOG performance status of 0 or 1.
  • Patient must demonstrate ability to be compliant with medical regimen.
  • Patient must not have active alcohol or substance abuse within 6 months of study entry.
  • Patient must not be enrolled on another investigational agent concurrently.
  • Patient must not have any medical condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of the patient.

Exclusion Criteria:

  • See Inclusion criteria above
Both
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00914849
09-0713 / 201103429
No
No
Not Provided
Washington University School of Medicine
Washington University School of Medicine
Not Provided
Principal Investigator: John DiPersio, M.D., Ph.D. Washington University School of Medicine
Washington University School of Medicine
July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP