Campath/Fludarabine/Melphalan Transplant Conditioning for Non-Malignant Diseases - Full Text View

Purpose

The purpose of this study is to determine if treatment with alemtuzumab, fludarabine and melphalan followed by related/unrelated bone marrow, peripheral blood stem cell, or umbilical cord blood cell transplant will result in donor engraftment on day +100. It is also to determine major toxicities from this conditioning regimen, within the first 100 days after transplantation.

Condition	Intervention	Phase
Metabolic Disorders Hematologic, Immune, or Bone Marrow Disorders Hemoglobinopathies	Drug: Transplant conditioning regimen of alemtuzumab, fludarabine, and melphalan Drug: Transplant conditioning regimen of hydroxyurea, campath, fludarabine, thiotepa, & melphalan	Phase 1 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 Study of Hematopoietic Stem Cell Transplantation (HSCT) in Non-Malignant Disease Using a Reduced-Intensity Preparatory Regime

Resource links provided by NLM:

MedlinePlus related topics: Bone Marrow Diseases Metabolic Disorders

Drug Information available for: Thiotepa Hydroxyurea Melphalan Melphalan hydrochloride Fludarabine Fludarabine phosphate Alemtuzumab

U.S. FDA Resources

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

Primary Outcome Measures:

Donor engraftment as measured by chimerism [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: Yes ]
Major toxicities as graded by the CTC v3 [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Time to neutrophil and platelet engraftment as measured by complete blood counts [ Time Frame: Notapplicable ] [ Designated as safety issue: Yes ]
Incidence of acute graft-versus-host disease as measured by protocol grading scale [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: Yes ]
Incidence of chronic graft-versus-host disease as measured by protocol grading scale [ Time Frame: 2 years post-transplant ] [ Designated as safety issue: Yes ]
Long-term donor engraftment by donor chimerism [ Time Frame: 2 years post-transplant ] [ Designated as safety issue: Yes ]
Immune reconstitution by laboratory evaluations [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: Yes ]
Overall and disease free survival [ Time Frame: 2 years post-transplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	183
Study Start Date:	December 2001
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Matched related HSCT for hemoglobinopathies	Drug: Transplant conditioning regimen of alemtuzumab, fludarabine, and melphalan Day -22 Campath-1H 3 mg IV... Day -21 Campath-1H 10 mg IV... Day -20 Campath-1H 15 mg IV... Day -19 Campath-1H 20 mg IV... Day -8 Fludarabine 30mg/m2 IV... Day -7 Fludarabine 30mg/m2 IV... Day -6 Fludarabine 30mg/m2 IV... Day -5 Fludarabine 30mg/m2 IV... Day -4 Fludarabine 30mg/m2 IV... Day -3 Melphalan 140 mg/m2 IV... (dose modifications for patients <10 kgs) Procedure/Surgery: Hematopoietic stem cell infusion Bone marrow or peripheral blood stem cell infusion on Day 0 Other Names: Alemtuzumab Campath
Experimental: Unrelated HSCT for thalassemia	Drug: Transplant conditioning regimen of hydroxyurea, campath, fludarabine, thiotepa, & melphalan Day -50 to -21 Hydroxyurea 30mg/kg PO… Day -22 Campath-1H 3 mg IV... Day -21 Campath-1H 10 mg IV... Day -20 Campath-1H 15 mg IV... Day -19 Campath-1H 20 mg IV... Day -8 Fludarabine 30mg/m2 IV... Day -7 Fludarabine 30mg/m2 IV... Day -6 Fludarabine 30mg/m2 IV... Day -5 Fludarabine 30mg/m2 IV... Day -4 Fludarabine 30mg/m2 IV... Day -4 Thiotepa 8mg/kg IV… Day -3 Melphalan 140 mg/m2 IV... (dose modifications for patients <10 kgs) Procedure/Surgery: Hematopoietic stem cell infusion Bone marrow or umbilical cord blood stem cell infusion on Day 0 Other Names: Alemtuzumab Campath
Experimental: Minimally mismatched unrelated HSCT for hemoglobinopathies	Drug: Transplant conditioning regimen of hydroxyurea, campath, fludarabine, thiotepa, & melphalan Day -50 to -21 Hydroxyurea 30mg/kg PO… Day -22 Campath-1H 3 mg IV... Day -21 Campath-1H 10 mg IV... Day -20 Campath-1H 15 mg IV... Day -19 Campath-1H 20 mg IV... Day -8 Fludarabine 30mg/m2 IV... Day -7 Fludarabine 30mg/m2 IV... Day -6 Fludarabine 30mg/m2 IV... Day -5 Fludarabine 30mg/m2 IV... Day -4 Fludarabine 30mg/m2 IV... Day -4 Thiotepa 8mg/kg IV… Day -3 Melphalan 140 mg/m2 IV... (dose modifications for patients <10 kgs) Procedure/Surgery: Hematopoietic stem cell infusion Bone marrow or umbilical cord blood stem cell infusion on Day 0 Other Names: Alemtuzumab Campath
Experimental: Minor mismatched unrelated HSCT for non-malignant disorders	Drug: Transplant conditioning regimen of hydroxyurea, campath, fludarabine, thiotepa, & melphalan Day -50 to -21 Hydroxyurea 30mg/kg PO… Day -22 Campath-1H 3 mg IV... Day -21 Campath-1H 10 mg IV... Day -20 Campath-1H 15 mg IV... Day -19 Campath-1H 20 mg IV... Day -8 Fludarabine 30mg/m2 IV... Day -7 Fludarabine 30mg/m2 IV... Day -6 Fludarabine 30mg/m2 IV... Day -5 Fludarabine 30mg/m2 IV... Day -4 Fludarabine 30mg/m2 IV... Day -4 Thiotepa 8mg/kg IV… Day -3 Melphalan 140 mg/m2 IV... (dose modifications for patients <10 kgs) Procedure/Surgery: Hematopoietic stem cell infusion Bone marrow or umbilical cord blood stem cell infusion on Day 0 Other Names: Alemtuzumab Campath

Eligibility

Ages Eligible for Study:	up to 20 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Stratum 1: Patient must have a hemoglobinopathy receiving a matched related transplant with bone marrow or peripheral blood stem cells.

Stratum 2: Patient must have thalassemia receiving an unrelated donor transplant with bone marrow or umbilical cord blood stem cells.

Stratum 3: Patient must have a hemoglobinopathy receiving a minimally mismatched unrelated donor transplant with bone marrow or single or double umbilical cord blood product.

Stratum 4: Patient must have a non-malignant disorder (excluding hemoglobinopathy) receiving a minor mismatched unrelated donor transplant with bone marrow or single or double umbilical cord blood product.

All strata:

Recipient age < 21 years
Lansky/Karnofsky >/= 40
Adequate pulmonary, renal, liver, and other organ function as defined in protocol
Negative pregnancy test
Adequate total nucleated cell or CD34+ dose of product as defined in protocol
If sickle cell, Hemoglobin S <30%

Exclusion Criteria:

HIV positive
Invasive infection
Pregnancy/lactating

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00920972

Contacts

Contact: Lisa Murray, MA, CCRP

3144544240

Murray_L@kids.wustl.edu

Locations

United States, Arizona
Phoenix Children's Hospital	Recruiting
Phoenix, Arizona, United States, 85016
Principal Investigator: Roberta Adams, MD
United States, California
University of California	Recruiting
San Diego, California, United States, 92123
Principal Investigator: Eric Anderson, MD
United States, District of Columbia
George Washington University School of Medicine	Recruiting
Washington DC, District of Columbia, United States, 20010
Principal Investigator: David Jacobsohn, MD
United States, Florida
Miami Children's Hospital	Recruiting
Miami, Florida, United States, 33155
Contact: John A Fort, MD
Principal Investigator: Guillermo De Angulo, MD
University of Miami	Recruiting
Miami, Florida, United States, 33136
Principal Investigator: Martin Andreansky, MD
All Children's Hospital	Recruiting
St. Petersburg, Florida, United States, 33701
Principal Investigator: Gregory Hale, MD
United States, Illinois
Children's Memorial Hospital	Recruiting
Chicago, Illinois, United States, 60614
Principal Investigator: Sonali Chaudhury, MD
United States, Indiana
Indiana University School of Medicine	Recruiting
Indianapolis, Indiana, United States, 46202
Principal Investigator: Paul Haut, MD
United States, Louisiana
Louisiana State University	Recruiting
New Orleans, Louisiana, United States, 70112
Principal Investigator: Lolie Yu, MD
United States, Missouri
Children's Mercy Hospitals and Clinics	Recruiting
Kansas City, Missouri, United States, 64108
Principal Investigator: Jignesh Dalal, MD
Washington University School of Medicine (in St. Louis)	Recruiting
St. Louis, Missouri, United States, 63110
Contact: Shalini Shenoy, MD 314-454-6018 shenoy@wustl.edu
Contact: Lisa Murray, MA, CCRP 3144544240 Murray_L@kids.wustl.edu
United States, New Jersey
Hackensack University Medical Center	Recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Columbia University Medical Center	Recruiting
New York, New York, United States, 10032
Contact: Monica Bhatia, MD
Principal Investigator: Monica Bhatia, MD
United States, North Carolina
Carolinas Medical Center	Recruiting
Charlotte, North Carolina, United States, 28232
Principal Investigator: Andrew Gilman, MD
United States, Texas
Cook Children's Health Care System	Recruiting
Fort Worth, Texas, United States, 76104
Principal Investigator: Richard P Howrey, MD
Texas Transplant Institute	Recruiting
San Antonio, Texas, United States, 78229
Principal Investigator: Ka-Wah Chan, MD
United States, Utah
Primary Children's Medical Center	Recruiting
Salt Lake City, Utah, United States, 84113
Principal Investigator: Michael Pulsipher, MD
Canada, British Columbia
British Columbia Children's Hospital	Recruiting
Vancouver, British Columbia, Canada, V6H3V4
Principal Investigator: Jeffrey Davis, MD

Sponsors and Collaborators

Washington University School of Medicine

St. Louis Children's Hospital

Investigators

Principal Investigator:

Shalini Shenoy, MD

Washington University School of Medicine (in St. Louis)

More Information

Publications:

Bhatla D, Davies SM, Shenoy S, Harris RE, Crockett M, Shoultz L, Smolarek T, Bleesing J, Hansen M, Jodele S, Jordan M, Filipovich AH, Mehta PA. Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman-Diamond syndrome. Bone Marrow Transplant. 2008 Aug;42(3):159-65. Epub 2008 May 26.

Hansen MD, Filipovich AH, Davies SM, Mehta P, Bleesing J, Jodele S, Hayashi R, Barnes Y, Shenoy S. Allogeneic hematopoietic cell transplantation (HCT) in Hurler's syndrome using a reduced intensity preparative regimen. Bone Marrow Transplant. 2008 Feb;41(4):349-53. Epub 2007 Nov 19.

Rao A, Kamani N, Filipovich A, Lee SM, Davies SM, Dalal J, Shenoy S. Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning. Blood. 2007 Jan 1;109(1):383-5. Epub 2006 Sep 21.

Shenoy S, Grossman WJ, DiPersio J, Yu LC, Wilson D, Barnes YJ, Mohanakumar T, Rao A, Hayashi RJ. A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders. Bone Marrow Transplant. 2005 Feb;35(4):345-52.

Responsible Party:	Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00920972 History of Changes
Other Study ID Numbers:	01-0923
Study First Received:	June 15, 2009
Last Updated:	January 14, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:

Bone marrow
Transplant
Transplantation
Hematopoietic
Umbilical cord
Related

Unrelated
Reduced
Non-myeloablative
Nonmyeloablative
Non-malignant
Nonmalignant

Additional relevant MeSH terms:

Bone Marrow Diseases
Hemoglobinopathies
Metabolic Diseases
Hematologic Diseases
Genetic Diseases, Inborn
Fludarabine
Fludarabine monophosphate
Alemtuzumab
Hydroxyurea
Melphalan
Thiotepa
Campath 1G
Vidarabine
Antineoplastic Agents
Therapeutic Uses

Pharmacologic Actions
Antisickling Agents
Hematologic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents

ClinicalTrials.gov processed this record on May 22, 2013