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

The Washington University

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: GVHD Regimen B: BM Recipients; Drug: Treatment Plan 1: Stratum 1; Drug: GVHD Regimen A: UCB Recipients; Drug: Treatment Plan 2: Strata 2, 3, or 4

Study type: Interventional

Funder types: Other

Identifiers

NCT00920972

201110144

Details and patient eligibility

About

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.

Full 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.

Enrollment: 220 estimated patients

Sex: All

Ages: Under 20 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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220 participants in 4 patient groups

Stratum 1

Experimental group

Description:

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

Treatment:

Drug: Treatment Plan 1: Stratum 1

Drug: GVHD Regimen B: BM Recipients

Stratum 2

Experimental group

Description:

Recipient with transfusion dependent thalassemia. Related or unrelated. 8/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB

Treatment:

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

Drug: GVHD Regimen A: UCB Recipients

Drug: GVHD Regimen B: BM Recipients

Stratum 3

Experimental group

Description:

Recipient with hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB

Treatment:

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

Drug: GVHD Regimen A: UCB Recipients

Drug: GVHD Regimen B: BM Recipients

Stratum 4

Experimental group

Description:

Recipient with non-malignant disorder, excluding hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB

Treatment:

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

Drug: GVHD Regimen A: UCB Recipients

Drug: GVHD Regimen B: BM Recipients