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Campath/Fludarabine/Melphalan Transplant Conditioning for Non-Malignant Diseases

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ClinicalTrials.gov Identifier: NCT00920972

Recruitment Status : Recruiting

First Posted : June 16, 2009

Last Update Posted : January 31, 2023

See Contacts and Locations

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

St. Louis Children's Hospital

Information provided by (Responsible Party):

Washington University School of Medicine

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Metabolic Disorders Hematologic, Immune, or Bone Marrow Disorders Hemoglobinopathies Non-malignant Disorders	Drug: Treatment Plan 1: Stratum 1 Drug: Treatment Plan 2: Strata 2, 3, or 4 Drug: GVHD Regimen A: UCB Recipients Drug: GVHD Regimen B: BM Recipients	Phase 1 Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	220 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (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
Study Start Date :	December 2001
Estimated Primary Completion Date :	December 2026
Estimated Study Completion Date :	December 2031

Arms and Interventions

Arm	Intervention/treatment
Experimental: Stratum 1 Recipients with non-malignant disorders, excluding thalassemia. Related or unrelated 8/8 HLA-matched bone marrow	Drug: Treatment Plan 1: Stratum 1 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... Drug: GVHD Regimen B: BM Recipients 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	Drug: Treatment Plan 2: Strata 2, 3, or 4 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... Drug: GVHD Regimen A: UCB Recipients 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 Drug: GVHD Regimen B: BM Recipients 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 3 Recipient with hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB	Drug: Treatment Plan 2: Strata 2, 3, or 4 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... Drug: GVHD Regimen A: UCB Recipients 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 Drug: GVHD Regimen B: BM Recipients 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 4 Recipient with non-malignant disorder, excluding hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB	Drug: Treatment Plan 2: Strata 2, 3, or 4 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... Drug: GVHD Regimen A: UCB Recipients 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 Drug: GVHD Regimen B: BM Recipients 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

Outcome Measures

Primary Outcome Measures :

Donor engraftment as measured by chimerism [ Time Frame: 100 days post-transplant ]
Engraftment is measured in myeloid and lymphoid lineage cells
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

Secondary Outcome Measures :

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
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
Incidence of chronic graft-versus-host disease as measured by protocol grading scale [ Time Frame: 2 years post-transplant ]
cGVHD classified per Schulman et al. Am J Med 69: 204-17, 1980.
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.
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.
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.

Eligibility Criteria

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Ages Eligible for Study:	up to 20 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00920972

Contacts

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Contact: Stephanie Hyde, CCRP	3142861180	stephanie.day@wustl.edu

Locations

Show 18 study locations

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United States, Arizona
Phoenix Children's Hospital	Recruiting
Phoenix, Arizona, United States, 85016
Principal Investigator: Roberta Adams, MD
United States, California
Children's Hospital of Orange County	Recruiting
Orange, California, United States, 92868
Contact: David Buchbinder, MD
Principal Investigator: David Buchbinder, MD
University of California	Recruiting
San Diego, California, United States, 92123
Principal Investigator: Eric Anderson, MD
United States, Connecticut
Yale School of Medicine	Recruiting
New Haven, Connecticut, United States, 06510
Contact: Niketa Shah, MD
Principal Investigator: Niketa Shah, MD
United States, District of Columbia
George Washington University School of Medicine	Recruiting
Washington, District of Columbia, United States, 20010
Principal Investigator: David Jacobsohn, MD
United States, Florida
University of Miami	Recruiting
Miami, Florida, United States, 33136
Principal Investigator: Edward Dela Ziga, MD
Miami Children's Hospital	Recruiting
Miami, Florida, United States, 33155
Principal Investigator: Kamar Godder, MD
All Children's Hospital	Recruiting
Saint Petersburg, Florida, United States, 33701
Principal Investigator: Gregory Hale, MD
United States, Illinois
Children's Memorial Hospital	Completed
Chicago, Illinois, United States, 60614
United States, Indiana
Indiana University School of Medicine	Recruiting
Indianapolis, Indiana, United States, 46202
Principal Investigator: Scott Goebel, MD
United States, Missouri
St. Louis University	Recruiting
Saint Louis, Missouri, United States, 63104
Contact: Deepika Bhatla, MD
Principal Investigator: Deepika Bhatla, MD
Washington University School of Medicine (in St. Louis)	Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Shalini Shenoy, MD 314-454-6018 shalinishenoy@wustl.edu
Contact: Stephanie Hyde, CCRP 3142861180 stephanie.day@wustl.edu
United States, New Jersey
Hackensack University Medical Center	Completed
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: Michael Kent, MD
United States, Oklahoma
The University of Oklahoma	Completed
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
Texas Transplant Institute	Recruiting
San Antonio, Texas, United States, 78229
Principal Investigator: Troy Quigg, MD
Canada
University of Calgary	Recruiting
Calgary, Canada
Contact: Gregory Guilcher, MD
Principal Investigator: Gregory Guilcher, MD

Sponsors and Collaborators

Washington University School of Medicine

St. Louis Children's Hospital

Investigators

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Principal Investigator:	Shalini Shenoy, MD	Washington University School of Medicine (in St. Louis)

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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Responsible Party:	Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00920972
Other Study ID Numbers:	201110144
First Posted:	June 16, 2009 Key Record Dates
Last Update Posted:	January 31, 2023
Last Verified:	January 2023

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:

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Hemoglobinopathies Bone Marrow Diseases Metabolic Diseases Disease	Pathologic Processes Hematologic Diseases Genetic Diseases, Inborn

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