Expanded Use of G-CSF Mobilized Donor CD34+ Selected Cells for Allogeneic Transplantation

NCT02258490 | Unknown

• 2 other identifiers: IRB00051037EPIC-HPC001
• Study Type: expanded_access
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Allogeneic hematopoietic stem cell transplantation (HSCT) is an established form of treatment for hematological abnormalities. Poor graft function, occurs when there poor donor engraftment. A second infusion of unselected donor hematopoietic stem cells (HSC) can result in improvement, but can potentially increase the incidence of graft versus host disease. Cluster of differentiation 34+ (CD34+) selected stem cells depleted of T-cells is an attractive alternative for treatment of poor graft function as it may be associated with less Graft versus Host Disease (GVHD) and enhanced count recovery. The investigators are using the Miltenyi CliniMACS device and CD34 cell selection reagents for the preparation of allogeneic hematopoietic progenitor cell (HPC) transplants for patients who have had prior stem cell transplants and require a stem cell "boost" from the original donor.

Conditions

Chronic Myeloid Leukemia; Myelodysplastic Syndrome; Acute Myeloid Leukemia

Keywords

chronic myeloid leukemia; myelodysplastic syndrome; acute myeloid leukemia; CD34+ cell mobilization therapy; graft versus host disease; allogeneic hematopoietic stem cell; G-CSF

Interventions

G-CSF mobilized CD34+ selected cells for transplantation BIOLOGICAL

After screening and enrollment, donor will receive mobilization therapy with G-CSF (10 ug/Kg S/C daily x5-6 days) using standard National Marrow Donor Program guidelines. CD34+ cell selection will be performed according to procedures given in CliniMACS Operating Manual and institutional Standard Operating Procedures. If storage after CD34+ selection is necessary, product will be kept in a monitored refrigerator. During storage, leukocyte concentration should not exceed 2 x 108 cells/ml using platelet poor plasma to adjust cell concentration. If donor's plasma is not available, CliniMACS buffer will be used. Cell processing will be performed by personnel trained by Miltenyi on CliniMACS system prior to initiation of clinical product selection. After tests are performed and product passes release criteria, patient will receive final product. No conditioning regimen will be administered prior to cell infusion.

Eligibility Criteria

• Age: 17 Years - 75 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Donors must be eligible and approved for a hematopoietic stem cell graft according to institutional criteria (related donor) or NMDP criteria (volunteer unrelated donor)
• Donors must be ≥ 17 years old and ≤ 75 years old
• Donors must be agreeable to receive G-CSF for CD34 cell mobilization and undergo apheresis for the second donation of peripheral blood mononuclear cells (PBMC)
• Donor must have adequate peripheral venous catheter access for apheresis or must agree to placement of a central catheter
• The following laboratory tests/evaluations will be performed for all donors registered in the study. Additional evaluations/studies may also be performed by the site as dictated by the donor's clinical situation or standard practice for monitoring normal donors
• History and physical examination
• Automated complete blood count (WBC, red blood cells \[RBC\], hematocrit, hemoglobin) with differential and platelet counts
• Serum chemistries panel including electrolytes, glucose, blood urea nitrogen (BUN), alanine aminotransferase (ALT), creatinine, bilirubin, alkaline phosphatase, lactate dehydrogenase (LDH) and albumin. Electrolytes to include sodium, potassium, chloride, carbon dioxide, calcium and magnesium.
• Infections disease titers by FDA licensed tests for:
• Cytomegalovirus (CMV) antibody
• Hepatitis panel (Hepatitis B including HBsAg, HBcAb \[immunoglobulin M {IgM} and immunoglobulin G {IgG}\]; hepatitis C antibody)
• HIV 1+2 antibodies
• Hepatitis C virus (HCV) antibodies
• Human T-lymphotropic virus (HTLV) I/II antibodies
• Rapid plasmin reagin (RPR)

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (11)

• Davies SM, Weisdorf DJ, Haake RJ, Kersey JH, McGlave PB, Ramsay NK, Blazar BR. Second infusion of bone marrow for treatment of graft failure after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1994 Jul;14(1):73-7.

  PMID: 7951123 BACKGROUND

• Elmaagacli AH, Peceny R, Steckel N, Trenschel R, Ottinger H, Grosse-Wilde H, Schaefer UW, Beelen DW. Outcome of transplantation of highly purified peripheral blood CD34+ cells with T-cell add-back compared with unmanipulated bone marrow or peripheral blood stem cells from HLA-identical sibling donors in patients with first chronic phase chronic myeloid leukemia. Blood. 2003 Jan 15;101(2):446-53. doi: 10.1182/blood-2002-05-1615. Epub 2002 Sep 12.

  PMID: 12393406 BACKGROUND

• Lang P, Handgretinger R, Niethammer D, Schlegel PG, Schumm M, Greil J, Bader P, Engel C, Scheel-Walter H, Eyrich M, Klingebiel T. Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia. Blood. 2003 Feb 15;101(4):1630-6. doi: 10.1182/blood-2002-04-1203. Epub 2002 Oct 10.

  PMID: 12393439 BACKGROUND

• Urbano-Ispizua A, Brunet S, Solano C, Moraleda JM, Rovira M, Zuazu J, de La Rubia J, Bargay J, Caballero D, Diez-Martin JL, Ojeda E, Perez de Oteiza JP, Ferra C, Espigado I, Alegre A, de La Serna J, Torres P, Riu C, Odriozola J, Rozman C, Sierra J, Garcia-Conde J, Montserrat E; Spanish Group of Allo-PBT. Allogeneic transplantation of CD34+-selected cells from peripheral blood in patients with myeloid malignancies in early phase: a case control comparison with unmodified peripheral blood transplantation. Bone Marrow Transplant. 2001 Aug;28(4):349-54. doi: 10.1038/sj.bmt.1703154.

  PMID: 11571506 BACKGROUND

• Larocca A, Piaggio G, Podesta M, Pitto A, Bruno B, Di Grazia C, Gualandi F, Occhini D, Raiola AM, Dominietto A, Bregante S, Lamparelli T, Tedone E, Oneto R, Frassoni F, Van Lint MT, Pogliani E, Bacigalupo A. Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. Haematologica. 2006 Jul;91(7):935-40.

  PMID: 16818281 BACKGROUND

• Tabilio A, Falzetti F, Zei T, De Ioanni M, Bonifacio E, Battelli F, Iacucci Ostini R, Ballanti S, Cimminiello M, Capponi M, Silvani C, Minelli O, Fettucciari K, Marconi P, Rosati E, Santucci A, Di Ianni M, Aversa F, Martelli MF. Graft engineering for allogeneic haploidentical stem cell transplantation. Blood Cells Mol Dis. 2004 Nov-Dec;33(3):274-80. doi: 10.1016/j.bcmd.2004.08.016.

  PMID: 15528144 BACKGROUND

• Markiewicz M, Holowiecki J, Wojnar J, Krawczyk-Kulis M, Jagoda K, Giebel S, Kruzel T. Allogeneic transplantation of selected peripheral CD34+ cells with controlled CD3+ cells add-back in high-risk patients. Transplant Proc. 2004 Dec;36(10):3194-9. doi: 10.1016/j.transproceed.2004.09.052.

  PMID: 15686727 BACKGROUND

• Oyekunle A, Koehl U, Schieder H, Ayuk F, Renges H, Fehse N, Zabelina T, Fehse B, Klingebiel T, Sputtek A, Zander A, Kroger N. CD34(+)-selected stem cell boost for delayed or insufficient engraftment after allogeneic stem cell transplantation. Cytotherapy. 2006;8(4):375-80. doi: 10.1080/14653240600735784.

  PMID: 16923613 BACKGROUND

• Ringhoffer M, Wiesneth M, Harsdorf S, Schlenk RF, Schmitt A, Reinhardt PP, Moessner M, Grimminger W, Mertens T, Reske SN, Dohner H, Bunjes D. CD34 cell selection of peripheral blood progenitor cells using the CliniMACS device for allogeneic transplantation: clinical results in 102 patients. Br J Haematol. 2004 Aug;126(4):527-35. doi: 10.1111/j.1365-2141.2004.05062.x.

  PMID: 15287946 BACKGROUND

• Kao GS, Kim HT, Daley H, Ritz J, Burger SR, Kelley L, Vierra-Green C, Flesch S, Spellman S, Miller J, Confer D. Validation of short-term handling and storage conditions for marrow and peripheral blood stem cell products. Transfusion. 2011 Jan;51(1):137-47. doi: 10.1111/j.1537-2995.2010.02758.x.

  PMID: 20609197 BACKGROUND

• Antonenas V, Garvin F, Webb M, Sartor M, Bradstock KF, Gottlieb D. Fresh PBSC harvests, but not BM, show temperature-related loss of CD34 viability during storage and transport. Cytotherapy. 2006;8(2):158-65. doi: 10.1080/14653240600620994.

  PMID: 16698689 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Graft vs Host Disease

Interventions

Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Immune System Diseases

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative

Study Officials

• Edmund Waller, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: expanded access
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 16, 2014
• First Posted: October 7, 2014
• Last Updated: March 15, 2022

Record last verified: 2022-02

Locations

US (1)