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NCT Number: NCT00920972

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

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.

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Key information

Conditions

Metabolic Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hematologic, Immune, or Bone Marrow Disorders Hemic and Lymphatic Diseases Hemoglobinopathies Metabolic Diseases Non-malignant Disorders Nutritional and Metabolic Diseases

Age range

Up to 20 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

BC Children's Hospital, Vancouver, British Columbia, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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...

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...

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

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

Primary outcomes

  1. Donor engraftment as measured by chimerism

    Time frame: 100 days post-transplant

    Engraftment is measured in myeloid and lymphoid lineage cells

  2. 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 outcomes

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Ian Snyder, CCRP

CONTACT

[email protected]

3142735953

Lissy Keller, CCRP

CONTACT

[email protected]

3142861168

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Collaborators

  • St. Louis Children's Hospital

Registry information

Official study title

A Study of Hematopoietic Stem Cell Transplantation (HSCT) in Non-Malignant Disease Using a Reduced-Intensity Preparatory Regime

Important dates

Study start
2001
Primary completion
2026
Study completion
2031
First posted
Jun 16, 2009
Registry last updated
Mar 25, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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