Clinical trial NCT00920972: Campath/Fludarabine/Melphalan Transplant Conditioning for Non-Malignant Diseases
Official title: A Study of Hematopoietic Stem Cell Transplantation (HSCT) in Non-Malignant Disease Using a Reduced-Intensity Preparatory Regime
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metabolic Disorders
Hematologic, Immune, or Bone Marrow Disorders
Hemoglobinopathies
Non-malignant Disorders
Keywords: Bone marrow
Transplant
Transplantation
Hematopoietic
Umbilical cord
Related
Unrelated
Reduced
Non-myeloablative
Nonmyeloablative
Non-malignant
Nonmalignant
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: St. Louis Children's Hospital
First posted: 2009-06-16
Enrollment: 220
Sex: ALL
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The hypothesis for this study is that a preparative regimen that maximizes host immunosuppression without myeloablation will be well tolerated and sufficient for engraftment of donor hematopoietic cells. It is also to determine major toxicities from these conditioning regimens, within the first 100 days after transplantation.

Detailed description: The study uses reduced intensity conditioning that is immune suppressive to achieve donor cell engraftment without exposure to radiation or high dose chemotherapy in children with non-malignant disorders. The intent is to minimize early and late regimen related toxicities in the context of a reduced intensity regimen.

In addition to maximizing opportunity for donor cell engraftment, the trial seeks to minimize toxicities associated with transplant such as graft versus host disease and employs GVHD prophylaxis that seeks to decrease rates of acute and chronic GVHD in the setting of matched and mismatched donor stem cell transplants from marrow and cord blood sources.

Eligibility criteria: Inclusion Criteria:

Stratum 1: Patient must have non-malignant disorder, excluding thalassemia. Must be receiving a 8/8 HLA-matched bone marrow, related or unrelated Stratum 2: Patient must have thalassemia receiving 8/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated.

Stratum 3: Patient must have a hemoglobinopathy receiving 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated.

Stratum 4: Patient must have a non-malignant disorder (excluding hemoglobinopathy) receiving 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated.

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

Primary outcomes:
measure: Donor engraftment as measured by chimerism
timeFrame: 100 days post-transplant
measure: Major toxicities as graded by the CTC v4
timeFrame: 100 days post-transplant
Secondary outcomes:
measure: Time to neutrophil and platelet engraftment as measured by complete blood counts
timeFrame: Post transplant
measure: Incidence of acute graft-versus-host disease as measured by protocol grading scale
timeFrame: 100 days post-transplant
measure: Incidence of chronic graft-versus-host disease as measured by protocol grading scale
timeFrame: 2 years post-transplant
measure: Long-term donor engraftment by donor chimerism
timeFrame: 2 years post-transplant
measure: Immune reconstitution by laboratory evaluations
timeFrame: 1 year post-transplant
measure: Overall and disease free survival
timeFrame: 2 years post-transplant
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Diego
country: United States
facility: University of California
state: California
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Washington
country: United States
facility: George Washington University School of Medicine
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine (in St. Louis)
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: The University of Oklahoma
state: Oklahoma
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Calgary
country: Canada
facility: University of Calgary
Study officials:
affiliation: Washington University School of Medicine (in St. Louis)
name: Shalini Shenoy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1038/bmt.2008.151. Epub 2008 May 26.
citation: 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. doi: 10.1038/sj.bmt.1705926. Epub 2007 Nov 19.
citation: 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. doi: 10.1182/blood-2006-05-025072. Epub 2006 Sep 21.
citation: 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. doi: 10.1038/sj.bmt.1704795.
citation: King AA, Kamani N, Bunin N, Sahdev I, Brochstein J, Hayashi RJ, Grimley M, Abraham A, Dioguardi J, Chan KW, Douglas D, Adams R, Andreansky M, Anderson E, Gilman A, Chaudhury S, Yu L, Dalal J, Hale G, Cuvelier G, Jain A, Krajewski J, Gillio A, Kasow KA, Delgado D, Hanson E, Murray L, Shenoy S. Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies. Am J Hematol. 2015 Dec;90(12):1093-8. doi: 10.1002/ajh.24183. Epub 2015 Oct 6.