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* 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

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

AMD3100

Leukopheresis

Stem cell transplant

John DiPersio, M.D., Ph.D.

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.

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

-Blood samples for pharmacokinetics were drawn on the following schedule:

* prior to IV infusion
* 15 minutes after start of infusion
* 30 minutes after start of infusion
* 1 hour after start of infusion
* 4 hours after start of infusion
* 6 hours after start of infusion
* 9 hours after start of infusion
* 24 hours after start of infusion

Measured by determine the first 3 consecutive measurement of neutrophil count = 500/ul following conditioning regimen induced nadir.

Measured by determining the first of 3 consecutive measurements of platelet count = 20,000/ul without platelet transfusion support for 7 days.

Death that results from a transplant procedure related complication rather than from relapse of the underlying disease or unrelated cause.

Assessed and graded according to NCI Common Terminology for Adverse Events Version 3.0.

Washington University School of Medicine

* Day 1

  * AMD3100 320 ug/kg IV
  * Leukopheresis
* Day 2 (if PBSC collected is not sufficient)

  * AMD3100 320 ug/kg IV
  * Leukopheresis

Arm 1 - Donor

Arm 2 - Recipient

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

One recipient was not transplanted because of donor withdrawal of consent to collect a second day after a failed first day apheresis attempt.

3 donors failed to reach target after two collections and 1 donor withdrew consent after failing to reach the goal on the first collection.

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

Number of Donors Who Experience Grade 3-4 Infusional Toxicity

Number of Recipients Who Have Neutrophil Engraftment

Pharmacokinetics of IV AMD3100 as Measured by the Mean Maximum Plasma Concentration (Cmax)

Pharmacokinetics of IV AMD3100 as Measured by Half Life

Pharmacokinetics of IV AMD3100 as Measured by Mean Area Under Curve (AUC)

Rate of Acute GVHD (Grade II-IV) in Recipients

Rate of Acute GVHD (Grade III-IV) in Recipients

Time to Neutrophil Engraftment for Recipients

Time to Platelet Engraftment for Recipients

Transplant Related Mortality Rate for Recipients

Grade 3 fatigue

Grade 3 thrombocytopenia

Grade 3 mucositis

Grade 3 GI fistula

Grade 3 increased transaminase

Grade 3 febrile neutropenia

Grade 3 bacteremia+

Grade 3 respiratory distress

Grade 3 renal failure

Grade 3-4 Toxicity for Recipients

8 patients are not evaluable because they were not alive for the outcome measure time frame.

Rate of Chronic GVHD in Recipients

Number of Donors Who Experience Grade 3-4 Mobilization Toxicity Due to Pheresis Procedure

* Day 1

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

  * AMD3100 320 ug/kg IV
  * Leukopheresis

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Intravenous (IV) AMD3100 for Mobilization and Matched Related Transplant for Advanced Hematological Malignancies	NCT00914849	Hematologic Neo...	AMD3100 Leukopheresis Stem cell trans...	18 Years - 65 Years	Washington University School of Medicine
Intravenous (IV) AMD3100 for Mobilization and Matched Related Transplant for Advanced Hematological Malignancies	NCT00914849	Hematologic Neo...	AMD3100 Leukopheresis Stem cell trans...	18 Years - 65 Years	Washington University School of Medicine

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