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
  Purpose
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.

Condition Intervention Phase
Hematologic Neoplasms
Drug: AMD3100
Procedure: Leukopheresis
Procedure: Stem cell transplant
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 68
Study Start Date: August 2009
Study Completion Date: February 2012
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: AMD3100
Other Names:
  • Mozobil
  • Plerixafor
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

Procedure: Stem cell transplant

Detailed Description:
  • 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.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00914849

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: John DiPersio, M.D., Ph.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:
Broxmeyer HE, Hangoc G, Cooper S, Bridger G. Interference of the SDF-1/CXCR4 axis in mice with AMD3100 induces rapid high level mobilization of hematopoietic progenitor cells, and AMD3100 acts synergistically with G-CSF and MIP-1 alpha to mobilize progenitors. Blood. 2001;96:3371a
Broxmeyer HE, Hangoc G, Cooper S, Li X, Bridger G, Clapp DW. AMD3100, an antagonist of CXCR4 and mobilizer of myeloid progenitor cells, is a potent mobilizer of competitive repopulating long term marrow self renewing stem cells in mice. Blood. 2002;98:2397a
Liles WC, Broxmeyer HE, Rodger E, Hubel K, Cooper S, Hangoc G, Bridger GJ, Henson GW, Calandra G, Dale D. Leucocytosis and mobilization of pluripotent hematopoietic progenitor cells in healthy volunteers induced by single dose administration of AMD-3100, a CXCR4 antagonist. Blood. 2001;96:3071a
Devine S, Adkins D, Khoury H, Vij R, Goodnough LT, Graubert T, Tomasson M, Blum W, DiPersio J, Brown R. Mobilization of donors with GM-CSF plus G-CSF or GM-CSF alone results in significantly different graft composition compared to G-CSF alone. Blood. 2002;100:825a

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00914849     History of Changes
Other Study ID Numbers: 09-0713 / 201103429 
Study First Received: June 1, 2009
Results First Received: July 14, 2016
Last Updated: July 14, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Hematologic Diseases
JM 3100
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 23, 2016