Have you or your loved ones been diagnosed with hematologic, immune, or bone marrow disorders?

You may be eligible to participate in a hematologic, immune, or bone marrow disorders clinical trial.

Have you or your loved ones been diagnosed with hematologic, immune, or bone marrow disorders? You may be eligible to participate in a hematologic, immune, or bone marrow disorders clinical trial.

What is a clinical trial? Is participating in a clinical trial right for you? Learn more

Hematologic, Immune, or Bone Marrow Disorders Clinical Trial

NCT00920972 | Phase 1 phase 2 | Interventional

Have you or your loved ones been diagnosed with hematologic, immune, or bone marrow disorders?

You may be eligible to participate in a hematologic, immune, or bone marrow disorders clinical trial.

Have you or your loved ones been diagnosed with hematologic, immune, or bone marrow disorders? You may be eligible to participate in a hematologic, immune, or bone marrow disorders clinical trial.

Recruiting

Male & Female

Up to 20

Years old

This study is looking to recruit 220 Participants

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.

Show me more details

Details for the study

Brief Title

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

Official Title

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

Brief Summary

The hypothesis for this study is that a preparative regimen that maximizes host <br /> immunosuppression without myeloablation will be well tolerated and sufficient for engraftment <br /> of donor hematopoietic cells. It is also to determine major toxicities from these <br /> conditioning regimens, within the first 100 days after transplantation.

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.

Treatments and/or Procedures

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...

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...

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

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

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.

Primary

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

Primary

Donor engraftment as measured by chimerism

Engraftment is measured in myeloid and lymphoid lineage cells

100 days post-transplant

Secondary

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

Post transplant

Secondary

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.

2 years post-transplant

Secondary

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.

2 years post-transplant

Secondary

Immune reconstitution by laboratory evaluations

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.

1 year post-transplant

Secondary

Overall and disease free survival

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.

2 years post-transplant

Secondary

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

100 days post-transplant

Study 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