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

ConditionsMetabolic DisordersHematologic, Immune, or Bone Marrow DisordersHemoglobinopathiesNon-malignant Disorders
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
AgeUp to 20
SponsorWashington University School of Medicine

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Recipient age < 21 years

Lansky/Karnofsky >/= 40

Adequate pulmonary, renal, liver, and other organ function as defined in protocol

Negative pregnancy test

Disqualifiers

HIV positive

Invasive infection

Pregnancy/lactating

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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

Treatment groups

220 Participants
are divided into 4 treatment groups
Group A: Stratum 1Experimental treatment 2 interventions
Group B: Stratum 2Experimental treatment 3 interventions
Group C: Stratum 3Experimental treatment 3 interventions
Group D: Stratum 4Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Donor engraftment as measured by chimerism

Engraftment is measured in myeloid and lymphoid lineage cells

Time frame
100 days post-transplant
2

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

Time frame
100 days post-transplant

Secondary outcomes

1

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

Defined as an ANC \>500/microliter and platelets \>20,000 or 50,000/microliter depending on disorder

Time frame
Post transplant
2

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

aGVHD - involving the skin, gut and liver. Classified according to grading described by Thomas et al. NEJM 1975; 292:895-902

Time frame
100 days post-transplant
3

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

cGVHD classified per Schulman et al. Am J Med 69: 204-17, 1980.

Time frame
2 years post-transplant
4

Long-term donor engraftment by donor chimerism

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.

Time frame
2 years post-transplant

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Washington University School of Medicine

Lead sponsor

St. Louis Children's Hospital

Collaborator

Source ClinicalTrials.gov
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