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

NCT00920972 | Recruiting Phase 1 DMC

• 1 other identifier: 201110144
• Study Type: interventional
• Target: 220
• Locations: 2 countries
• Sites: 28

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.

Conditions

Metabolic Disorders; Hemoglobinopathies; Non-malignant Disorders; Hematologic, Immune, or Bone Marrow Disorders

Keywords

Bone marrow; Transplant; Transplantation; Hematopoietic; Umbilical cord; Related; Unrelated; Reduced; Non-myeloablative; Nonmyeloablative; Non-malignant; Nonmalignant

Outcome Measures

Primary Outcomes (2)

• Donor engraftment as measured by chimerism

  Engraftment is measured in myeloid and lymphoid lineage cells

  100 days post-transplant

• Major toxicities as graded by the CTC v4

  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 Outcomes (6)

• Time to neutrophil and platelet engraftment as measured by complete blood counts

  Post transplant

• Incidence of acute graft-versus-host disease as measured by protocol grading scale

  100 days post-transplant

• Incidence of chronic graft-versus-host disease as measured by protocol grading scale

  2 years post-transplant

• Long-term donor engraftment by donor chimerism

  2 years post-transplant

• Immune reconstitution by laboratory evaluations

  1 year post-transplant

Study Arms (4)

Stratum 1

EXPERIMENTAL

Recipients with non-malignant disorders, excluding thalassemia. Related or unrelated 8/8 HLA-matched bone marrow

Drug: Treatment Plan 1: Stratum 1; Drug: GVHD Regimen B: BM Recipients

Stratum 2

EXPERIMENTAL

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; Drug: GVHD Regimen A: UCB Recipients; Drug: GVHD Regimen B: BM Recipients

Stratum 3

EXPERIMENTAL

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; Drug: GVHD Regimen A: UCB Recipients; Drug: GVHD Regimen B: BM Recipients

Stratum 4

EXPERIMENTAL

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; Drug: GVHD Regimen A: UCB Recipients; Drug: GVHD Regimen B: BM Recipients

Interventions

GVHD Regimen B: BM Recipients DRUG

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

Stratum 1; Stratum 2; Stratum 3; Stratum 4

Treatment Plan 2: Strata 2, 3, or 4 DRUG

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...

Stratum 2; Stratum 3; Stratum 4

GVHD Regimen A: UCB Recipients DRUG

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

Stratum 2; Stratum 3; Stratum 4

Treatment Plan 1: Stratum 1 DRUG

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...

Stratum 1

Eligibility Criteria

• Age: Up to 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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%

You may not qualify if:

• HIV positive
• Invasive infection
• Pregnancy/lactating

Sponsors & Collaborators

• St. Louis Children's Hospital: collaborator
• Washington University School of Medicine: lead

Study Sites (28)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

University of California

San Diego, California, 92123, United States

RECRUITING

Yale School of Medicine

New Haven, Connecticut, 06510, United States

RECRUITING

George Washington University School of Medicine

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Nemours Children's Health

Jacksonville, Florida, 32207, United States

COMPLETED

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Miami Children's Hospital

Miami, Florida, 33155, United States

COMPLETED

All Children's Hospital

St. Petersburg, Florida, 33701, United States

COMPLETED

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

COMPLETED

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

RECRUITING

Children's Hospital of New Orleans

New Orleans, Louisiana, 70118, United States

COMPLETED

Children's Mercy

Kansas City, Missouri, 64108, United States

COMPLETED

St. Louis University

St Louis, Missouri, 63104, United States

RECRUITING

Washington University School of Medicine (in St. Louis)

St Louis, Missouri, 63110, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

COMPLETED

Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Carolinas Medical Center

Charlotte, North Carolina, 28232, United States

COMPLETED

Duke Children's Hospital

Durham, North Carolina, 27705, United States

COMPLETED

The University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

COMPLETED

University of Pittsburg

Pittsburgh, Pennsylvania, 15224, United States

COMPLETED

Cook Children's Hospital

Forth Worth, Texas, 76104, United States

COMPLETED

Texas Transplant Institute

San Antonio, Texas, 78229, United States

COMPLETED

University of Utah

Salt Lake City, Utah, 84132, United States

RECRUITING

BC Children's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

COMPLETED

University of Manitoba

Winnipeg, Manitoba, MB R3E 0T4, Canada

COMPLETED

University of Calgary

Calgary, Canada

COMPLETED

Related Publications (5)

• 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.

  PMID: 18500373 RESULT

• 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.

  PMID: 18026148 RESULT

• 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.

  PMID: 16990602 RESULT

• 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.

  PMID: 15592491 RESULT

• 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.

  PMID: 26348869 DERIVED

MeSH Terms

Conditions

Metabolic Diseases; Hemoglobinopathies

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Shalini Shenoy, MD

  Washington University School of Medicine (in St. Louis)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lissy Keller, CCRP

CONTACT

3142861168; kellerl@wustl.edu

Ian Snyder, CCRP

CONTACT

3142735953; ian.s@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2009
• First Posted: June 16, 2009
• Study Start: December 1, 2001
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2031
• Last Updated: March 25, 2026

Record last verified: 2026-03

Locations

US (25); CA (3)