Study Evaluating AMD3100 for Transplantation of Sibling Donor Stem Cells in Patients With Hematological Malignancies

NCT00241358 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 03-0349
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if peripheral blood cells collected following AMD3100 mobilization can be used safely for hematopoietic cell transplantation into HLA-matched recipients.

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic; Leukemia, Lymphoblastic, Acute; Lymphocytic Leukemia, Chronic; Myelodysplastic Syndromes; Multiple Myeloma; Lymphoma, Non-Hodgkin; Hodgkin Disease

Keywords

Plerixafor; Stem cell transplantation; Stem cells; Mobilization

Outcome Measures

Primary Outcomes (3)

• Proportion of Donors From Whom a Sufficient Number of Cells for Transplantation Are Collected in no More Than 2 LP Procedures Following Mobilization With AMD3100 (Donor Only)

  -Defined as the proportion of donors collecting \>2.0x106 CD34+ cells/kg \[recipient weight\]

  Day 1-3

• Proportion of Recipients Who Experience Grade 2-4 Acute GVHD (Recipient Only)

  -Incidence and severity of acute GVHD (aGVHD) will be assessed based on the Seattle criteria

  By Day 100 after transplant

• Proportion of Recipients Who Successfully Engraft by Day +21 After Transplant (Recipient Only)

  -Defined as neutrophil count ≥ 500/ul following conditioning regimen induced nadir

  Day +21

Secondary Outcomes (6)

• Proportion of Recipients Who Experience Chronic GVHD (Recipient Only)

  Between Day +100 and +365 post-transplant

• Proportion of Recipients Who Experience Mortality Before Day 100 After Transplant (Recipient Only)

  100 days after transplant

• Quality of Life During Stem Cell Mobilization (Recipients Only)

  48-72 hours after last dose of AMD3100

• Proportion of Donors Who Experience Infusional Toxicity (Donor Only)

  Day +1 to +3 (SC donor arm) and Day -3 to +3 (IV donor arm)

• To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Cmax

  0 to 24 hours after dose of IV AMD3100

Study Arms (3)

Subcutaneous (SC) Treatment Plan - Donor

ACTIVE COMPARATOR

* Day 1: Mobilization with 240 mcg/kg SC AMD3100 and leukopheresis * If PBSC collected are not adequate, then donor will again be mobilized with AMD3100 and have leukopheresis collection on day 3.

Drug: AMD3100

Intravenous (IV) Treatment Plan - Donor

EXPERIMENTAL

* Day -3: Mobilization with 80-480 mcg/kg/day IV AMD3100 and PK analysis * Day 1: Mobilization with 240 mcg/kg/day SC AMD3100 and leukopheresis * If PBSC collected are not adequate, then donor will again be mobilized with AMD3100 and have leukopheresis collection on day 3.

Drug: AMD3100

Recipients

OTHER

* Conditioning Regimen * Cyclophosphamide 60mg/kg/day on Days -3 and -2 * TBI 550cGy on Day -1 * GVHD prophylaxis \*Cyclosporin 3.0mg/kg/day beginning on Day -1 then tapered through Day +100 * PBSC transplant on Day 0

Procedure: Stem Cell Transplant

Interventions

AMD3100 DRUG

Also known as: Plerixafor

Intravenous (IV) Treatment Plan - Donor; Subcutaneous (SC) Treatment Plan - Donor

Stem Cell Transplant PROCEDURE

Recipients

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Donor criteria:
• Donor is 18 to 70 years of age inclusive
• If female and of child-bearing age, must be:
• non-pregnant,
• not breast feeding and
• using adequate contraception
• Donor is a 6/6 HLA-matched sibling willing to donate peripheral blood stem cell 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 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
• Must be HIV-1 \& 2 antibody, HIV-1 antigen, and HTLV-I \& II antibody sero-negative, by FDA licensed test.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (4)

• Devine SM, Vij R, Rettig M, Todt L, McGlauchlen K, Fisher N, Devine H, Link DC, Calandra G, Bridger G, Westervelt P, Dipersio JF. Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction. Blood. 2008 Aug 15;112(4):990-8. doi: 10.1182/blood-2007-12-130179. Epub 2008 Apr 21.

  PMID: 18426988 BACKGROUND

• Devine SM, Flomenberg N, Vesole DH, Liesveld J, Weisdorf D, Badel K, Calandra G, DiPersio JF. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma. J Clin Oncol. 2004 Mar 15;22(6):1095-102. doi: 10.1200/JCO.2004.07.131.

  PMID: 15020611 BACKGROUND

• Flomenberg N, Devine SM, Dipersio JF, Liesveld JL, McCarty JM, Rowley SD, Vesole DH, Badel K, Calandra G. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood. 2005 Sep 1;106(5):1867-74. doi: 10.1182/blood-2005-02-0468. Epub 2005 May 12.

  PMID: 15890685 BACKGROUND

• Schroeder MA, Rettig MP, Lopez S, Christ S, Fiala M, Eades W, Mir FA, Shao J, McFarland K, Trinkaus K, Shannon W, Deych E, Yu J, Vij R, Stockerl-Goldstein K, Cashen AF, Uy GL, Abboud CN, Westervelt P, DiPersio JF. Mobilization of allogeneic peripheral blood stem cell donors with intravenous plerixafor mobilizes a unique graft. Blood. 2017 May 11;129(19):2680-2692. doi: 10.1182/blood-2016-09-739722. Epub 2017 Mar 14.

  PMID: 28292947 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Myelodysplastic Syndromes; Multiple Myeloma; Lymphoma, Non-Hodgkin; Hodgkin Disease

Interventions

plerixafor; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoma

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: John F. DiPersio, M.D., Ph.D.
• Organization: Washington University School of Medicine

jdipersi@wustl.edu

314-454-8603

Study Officials

• John F. DiPersio, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2005
• First Posted: October 18, 2005
• Study Start: May 1, 2004
• Primary Completion: December 1, 2009
• Study Completion: February 1, 2010
• Last Updated: June 6, 2017
• Results First Posted: June 6, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)