- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00920972
Campath/Fludarabine/Melphalan Transplant Conditioning for Non-Malignant Diseases
A Study of Hematopoietic Stem Cell Transplantation (HSCT) in Non-Malignant Disease Using a Reduced-Intensity Preparatory Regime
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Stephanie Hyde, CCRP
- Phone Number: 3142861180
- Email: stephanie.day@wustl.edu
Study Locations
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Calgary, Canada
- Recruiting
- University of Calgary
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Contact:
- Gregory Guilcher, MD
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Arizona
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Phoenix, Arizona, United States, 85016
- Recruiting
- Phoenix Children's Hospital
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California
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Orange, California, United States, 92868
- Recruiting
- Children's Hospital of Orange County
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Contact:
- David Buchbinder, MD
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Principal Investigator:
- David Buchbinder, MD
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San Diego, California, United States, 92123
- Recruiting
- University of California
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Connecticut
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New Haven, Connecticut, United States, 06510
- Recruiting
- Yale School of Medicine
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District of Columbia
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Washington, District of Columbia, United States, 20010
- Recruiting
- George Washington University School of Medicine
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Florida
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Miami, Florida, United States, 33136
- Recruiting
- University of Miami
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Principal Investigator:
- Edward Dela Ziga, MD
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Miami, Florida, United States, 33155
- Recruiting
- Miami Children's Hospital
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Principal Investigator:
- Kamar Godder, MD
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Saint Petersburg, Florida, United States, 33701
- Recruiting
- All Children's Hospital
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Illinois
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Chicago, Illinois, United States, 60614
- Completed
- Children's Memorial Hospital
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Indiana
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Indianapolis, Indiana, United States, 46202
- Recruiting
- Indiana University School of Medicine
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Principal Investigator:
- Scott Goebel, MD
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Missouri
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Saint Louis, Missouri, United States, 63104
- Recruiting
- St. Louis University
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Contact:
- Deepika Bhatla, MD
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Saint Louis, Missouri, United States, 63110
- Recruiting
- Washington University School of Medicine (in St. Louis)
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Contact:
- Stephanie Hyde, CCRP
- Phone Number: 3142861180
- Email: stephanie.day@wustl.edu
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New Jersey
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Hackensack, New Jersey, United States, 07601
- Completed
- Hackensack University Medical Center
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New York
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New York, New York, United States, 10032
- Recruiting
- Columbia University Medical Center
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Contact:
- Monica Bhatia, MD
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North Carolina
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Charlotte, North Carolina, United States, 28232
- Recruiting
- Carolinas Medical Center
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73104
- Completed
- The University of Oklahoma
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Texas
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San Antonio, Texas, United States, 78229
- Recruiting
- Texas Transplant Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Stratum 1
Recipients with non-malignant disorders, excluding thalassemia.
Related or unrelated 8/8 HLA-matched bone marrow
|
Day -50 to -21: Hydroxyurea 30mg/kg PO q day Day -22: Campath-1H 3 mg IV or SQ... Day -21: Campath-1H 10 mg IV or SQ... Day -20: Campath-1H 15 mg IV or SQ... Day -19: Campath-1H 20 mg IV or SQ... 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 on Day 0...
Day -3: Begin Tacrolimus or cyclosporine Begin MMF Day -1: Abatacept 10mg/kg IV Day +1: Methotrexate 7.5mg/m2 IV Day +3: Methotrexate 7.5mg/m2 IV Day +5: Abatacept 10mg/kg IV Day +6: Methotrexate 7.5mg/m2 IV Day +14: Abatacept 10mg/kg IV Day +28: Abatacept 10mg/kg IV Day +60: Abatacept 10mg/kg IV Day +100: Abatacept 10mg/kg IV Day +180: Abatacept 10mg/kg IV Day +270: Abatacept 10mg/kg IV Day +365: Abatacept 10mg/kg IV
|
EXPERIMENTAL: Stratum 2
Recipient with transfusion dependent thalassemia.
Related or unrelated.
8/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
|
Day -3: Begin Tacrolimus or cyclosporine Begin MMF Day -1: Abatacept 10mg/kg IV Day +1: Methotrexate 7.5mg/m2 IV Day +3: Methotrexate 7.5mg/m2 IV Day +5: Abatacept 10mg/kg IV Day +6: Methotrexate 7.5mg/m2 IV Day +14: Abatacept 10mg/kg IV Day +28: Abatacept 10mg/kg IV Day +60: Abatacept 10mg/kg IV Day +100: Abatacept 10mg/kg IV Day +180: Abatacept 10mg/kg IV Day +270: Abatacept 10mg/kg IV Day +365: Abatacept 10mg/kg IV
Day -50 to -21: Hydroxyurea 30mg/kg PO q day… Day -22: Campath-1H 3 mg IV or SQ... Day -21: Campath-1H 10 mg IV or SQ... Day -20: Campath-1H 15 mg IV or SQ... Day -19: Campath-1H 20 mg IV or SQ... 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 on day 0...
Day -3: Begin Tacrolimus or cyclosporine Begin MMF Day -1: Abatacept 10mg/kg IV Day +5: Abatacept 10mg/kg IV Day +14: Abatacept 10mg/kg IV Day +28: Abatacept 10mg/kg IV Day +60: Abatacept 10mg/kg IV Day +100: Abatacept 10mg/kg IV
|
EXPERIMENTAL: Stratum 3
Recipient with hemoglobinopathy Related or unrelated.
7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
|
Day -3: Begin Tacrolimus or cyclosporine Begin MMF Day -1: Abatacept 10mg/kg IV Day +1: Methotrexate 7.5mg/m2 IV Day +3: Methotrexate 7.5mg/m2 IV Day +5: Abatacept 10mg/kg IV Day +6: Methotrexate 7.5mg/m2 IV Day +14: Abatacept 10mg/kg IV Day +28: Abatacept 10mg/kg IV Day +60: Abatacept 10mg/kg IV Day +100: Abatacept 10mg/kg IV Day +180: Abatacept 10mg/kg IV Day +270: Abatacept 10mg/kg IV Day +365: Abatacept 10mg/kg IV
Day -50 to -21: Hydroxyurea 30mg/kg PO q day… Day -22: Campath-1H 3 mg IV or SQ... Day -21: Campath-1H 10 mg IV or SQ... Day -20: Campath-1H 15 mg IV or SQ... Day -19: Campath-1H 20 mg IV or SQ... 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 on day 0...
Day -3: Begin Tacrolimus or cyclosporine Begin MMF Day -1: Abatacept 10mg/kg IV Day +5: Abatacept 10mg/kg IV Day +14: Abatacept 10mg/kg IV Day +28: Abatacept 10mg/kg IV Day +60: Abatacept 10mg/kg IV Day +100: Abatacept 10mg/kg IV
|
EXPERIMENTAL: Stratum 4
Recipient with non-malignant disorder, excluding hemoglobinopathy Related or unrelated.
7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
|
Day -3: Begin Tacrolimus or cyclosporine Begin MMF Day -1: Abatacept 10mg/kg IV Day +1: Methotrexate 7.5mg/m2 IV Day +3: Methotrexate 7.5mg/m2 IV Day +5: Abatacept 10mg/kg IV Day +6: Methotrexate 7.5mg/m2 IV Day +14: Abatacept 10mg/kg IV Day +28: Abatacept 10mg/kg IV Day +60: Abatacept 10mg/kg IV Day +100: Abatacept 10mg/kg IV Day +180: Abatacept 10mg/kg IV Day +270: Abatacept 10mg/kg IV Day +365: Abatacept 10mg/kg IV
Day -50 to -21: Hydroxyurea 30mg/kg PO q day… Day -22: Campath-1H 3 mg IV or SQ... Day -21: Campath-1H 10 mg IV or SQ... Day -20: Campath-1H 15 mg IV or SQ... Day -19: Campath-1H 20 mg IV or SQ... 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 on day 0...
Day -3: Begin Tacrolimus or cyclosporine Begin MMF Day -1: Abatacept 10mg/kg IV Day +5: Abatacept 10mg/kg IV Day +14: Abatacept 10mg/kg IV Day +28: Abatacept 10mg/kg IV Day +60: Abatacept 10mg/kg IV Day +100: Abatacept 10mg/kg IV
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Donor engraftment as measured by chimerism
Time Frame: 100 days post-transplant
|
Engraftment is measured in myeloid and lymphoid lineage cells
|
100 days post-transplant
|
Major toxicities as graded by the CTC v4
Time Frame: 100 days post-transplant
|
Toxicity monitoring includes unanticipated side effects (new) and all severe irreversible toxicities Grade 3 and above unexpected Grade 4 and above - all toxicities that are possibly, probably or definitely related to protocol therapy All deaths irrespective of attribution
|
100 days post-transplant
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to neutrophil and platelet engraftment as measured by complete blood counts
Time Frame: Post transplant
|
Defined as an ANC >500/microliter and platelets >20,000 or 50,000/microliter depending on disorder
|
Post transplant
|
Incidence of acute graft-versus-host disease as measured by protocol grading scale
Time Frame: 100 days post-transplant
|
aGVHD - involving the skin, gut and liver.
Classified according to grading described by Thomas et al.
NEJM 1975; 292:895-902
|
100 days post-transplant
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Incidence of chronic graft-versus-host disease as measured by protocol grading scale
Time Frame: 2 years post-transplant
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cGVHD classified per Schulman et al.
Am J Med 69: 204-17, 1980.
|
2 years post-transplant
|
Long-term donor engraftment by donor chimerism
Time Frame: 2 years post-transplant
|
Donor chimerism is determined by PCR analysis after cell separation into lymphoid and myeloid lineage cells using antibodies.
Can also be detected by FISH analysis in the event of donor and recipient sex discrepancy.
|
2 years post-transplant
|
Immune reconstitution by laboratory evaluations
Time Frame: 1 year post-transplant
|
Immune reconstitution detected by absolute numbers of T cell phenotypes, B cells and NK cells.
T cell function determined by proliferative response to mitogens.
B cell function determined by evaluating anti-tetanus antibody titers.
|
1 year post-transplant
|
Overall and disease free survival
Time Frame: 2 years post-transplant
|
Overall survival is defined as survival with or without disease Event free survival is defined as disease free, severe GVHD free survival, monitoring quality of life and relevant parameters.
|
2 years post-transplant
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Shalini Shenoy, MD, Washington University School of Medicine (in St. Louis)
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 201110144
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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