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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Washington University School of Medicine
Sponsor:
Collaborator:
St. Louis Children's Hospital
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00920972
First received: June 15, 2009
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Metabolic Disorders
Hematologic, Immune, or Bone Marrow Disorders
Hemoglobinopathies
Non-malignant Disorders
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:


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 v4 [ 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: 220
Study Start Date: December 2001
Estimated Primary Completion Date: December 2018 (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 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...

GVHD Prophylaxis:

Starting day -3: Tacrolimus or cyclosporine... Days +1, +3, +6: Methotrexate

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 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...

GVHD Prophylaxis Options:

Regimen 1= Starting day -3: Tacrolimus or cyclosporine... Days +1, +3, +6: Methotrexate.... Starting on day +7: Prednisone...

OR Regimen 2 = Starting day -3: tacrolimus or cyclosporine Starting day -3: mycophenolate mofetil

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 IVor 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...

GVHD Prophylaxis Regimen:

Children < 6 years of age, BM recipients:

Regimen 1 = Starting day -3: tacro or CsA... Days +1, +3, +6: MTX... Starting day +7: prednisone...

Children >/=6 years, BM recipients:

Regimen 3 = Starting day -3: tacro or CsA... Days +1, +3, +6: MTX... Days -1, +5, +14, +28: abatacept...

UCB recipients:

Regimen 1 (described above) OR Regimen 2 = Starting day -3: tacro or CsA... Starting day -3: MMF

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 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...

GVHD Prophylaxis Regimen:

Children < 6 years of age, BM recipients:

Regimen 1 = Starting day -3: tacro or CsA... Days +1, +3, +6: MTX... Starting day +7: prednisone...

Children >/=6 years, BM recipients:

Regimen 3 = Starting day -3: tacro or CsA... Days +1, +3, +6: MTX... Days -1, +5, +14, +28: abatacept...

UCB recipients:

Regimen 1 (described above) OR Regimen 2 = Starting day -3: tacro or CsA... Starting day -3: MMF

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 <45%

Exclusion Criteria:

  • HIV positive
  • Invasive infection
  • Pregnancy/lactating
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Lisa Murray, MA, CCRP 3144544240 Murray_L@kids.wustl.edu

  Show 21 Study Locations
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:
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: April 16, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

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
Disease
Metabolic Diseases
Hemoglobinopathies
Pathologic Processes
Hematologic Diseases
Genetic Diseases, Inborn
Fludarabine
Fludarabine phosphate
Alemtuzumab
Melphalan
Hydroxyurea
Thiotepa
Vidarabine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antisickling Agents
Hematologic Agents

ClinicalTrials.gov processed this record on September 18, 2014