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Allogeneic Mixed Chimerism Stem Cell Transplantation Utilizing In Vivo and In Vitro Campath for Hemoglobinopathies and Bone Marrow Failure Syndromes

Phase 2
18 Years
Not Enrolling
Sickle Cell Anemia, Severe Aplastic Anemia, Paroxysmal Nocturnal Hemoglobinuria (PNH), Pure Red Cell Aplasia

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Trial Information

Allogeneic Mixed Chimerism Stem Cell Transplantation Utilizing In Vivo and In Vitro Campath for Hemoglobinopathies and Bone Marrow Failure Syndromes


Primary Objective(s):

1. Evaluate the feasibility in terms of mortality, occurrence of acute graft versus host
disease, and grades 3-4/4 toxicity of in vivo and in vitro Campath coupled with
concomitantly administered nonmyeloablative fludarabine, cyclophosphamide and total
body irradiation (TBI) followed by Human Leukocyte Antigen (HLA) 5-6/6 matched family
member allo peripheral blood stem cell transplant (PBSCT).

2. Evaluate the engraftment rate of HLA 5-6/6 matched family member patients who receive
in vivo Campath followed by concomitantly administered fludarabine, cyclophosphamide
and total body irradiation (TBI) as a conditioning regimen with Campath-treated
peripheral blood stem cells (in vitro and in vivo exposure).

Secondary Objective(s):

1. Evaluate the response rate and survival of patients who receive a non-myeloablative
conditioning regimen of in vivo Campath followed by concomitantly administered
fludarabine, cyclophosphamide and total body irradiation (TBI) with Campath-treated
peripheral blood stem cells.

2. Evaluate the recovery of immune function post engraftment with this regimen.

Inclusion Criteria:

- Patients must have their clinical material reviewed at the transplanting institution
and the diagnosis confirmed

- Performance status must be Cancer and Leukemia Group B (CALGB) Performance Status
(PS) 0, 1, or 2.

- Patients must have a 5/6 to 6/6 HLA matched family member donor who is evaluated and
deemed able to provide PBSCs and/or marrow by the transplant team. Donor must have <
50% Hemoglobin S (HgS) on hemoglobin electrophoresis. Cytomegalovirus (CMV) status
of the donor will be assessed, but not used as an exclusion criterion.

- Patients must meet the following laboratory parameters unless due to disease status
as determined by the treating physician:

1. bilirubin and hepatic transaminases and creatinine must be reviewed by the
transplantation center and deemed acceptable.

2. HIV antibody negative.

3. hematocrit, white cell count, platelet counts and hematologic status will be
reviewed by the treating physician before patient is deemed acceptable.

- Patient must agree to use some form of adequate birth control during the periods that
they receive chemotherapy and any post-chemotherapy medications related to the

- Patients must also have a resting multiple gated acquisition scan (MUGA) or
echocardiogram and Pulmonary Function Tests (PFTs) with Diffusing Capacity of the
Lung for Carbon Monoxide (DLCO) performed before transplant. Recommended minimum
standards include an Ejection Fraction (EF) greater than 40% and DLCO greater than
40% for this less toxic regimen.

- Appropriate cardiology or pulmonary consultations should be considered if the patient
has severe cardiac or lung disease at the initiation of therapy.

I) Hemoglobinopathies:

(a)Sickle Cell Anemia having history of one or more of the following despite treatment
with standard therapies such as hydroxyurea: i) 2 or more episodes of acute chest syndrome
since age 13 years ii) pulmonary hypertension as measured by tricuspid regurgitant jet
velocity of greater than 2.5m/s iii) 2 or more painful crisis per year requiring medical
care and analgesia in excess of what is needed at baseline.

iv) history of cerebrovascular accident (b)Thalassemia major: Those eligible will have
either cardiac or hepatic sequela of thalassemia as documented by biopsy or functional
studies. For those with hepatic damage, this would be an increase in size by 50% of the
liver or a doubling of the total bilirubin, aspartate transaminase (AST), alanine
aminotransferase (ALT), or alkaline phosphatase. To be eligible for transplant due to
cardiac damage, there must be evidence of left ventricular dysfunction as measured by MUGA
scan or echocardiography.

II) Bone marrow failure Disorders

1. Severe Aplastic Anemia: Cytopenia consisting of at least 2 of the following 3:
absolute neutrophil count less than 500/μL, platelet count less than 20,000/μL, and
reticulocyte count less than 50,000/μL.

2. Paroxysmal nocturnal hemoglobinuria (PNH): Patients must have a history of either
life-threatening thrombosis, cytopenia, transfusion dependence or recurrent,
debilitating hemolytic crisis

3. Pure red cell aplasia: Patients must be transfusion dependent.

Exclusion Criteria:

- pregnant or lactating women,

- patients with other major medical or psychiatric illnesses which the treating or
transplant physician feels could seriously compromise compliance to this protocol

- patients with known history of allergies to murine protein

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Engraftment rate as indicated by chimerism studies

Outcome Description:

Absolute Neutrophil Count (ANC) > 500/μL and platelets > 20,000/μL and hemoglobin level remaining above 10 g/dL without transfusion support, with tests showing at least 2.5% donor cells present. Primary graft failure is defined as absence of establishment of adequate donor hematopoiesis by day 42 with bone marrow cellularity < 5%, peripheral White Blood Count (WBC) < 500/μL, peripheral ANC < 100/μL, and/or platelets < 10,000/μL by day 120 with absence of megakaryocytes in the bone marrow (in the absence of disease relapse). Mixed chimerism is defined as 2.5% to 97.5% donor stem cells in the microchimerism, Restriction Fragment Length Polymorphism (RFLP), or Florescence In Situ Hybridization (FISH) assay used to determine the origination of the stem cells (donor or recipient).

Outcome Time Frame:

1 year post transplant

Safety Issue:


Principal Investigator

David A. Rizzieri, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Duke Cancer Institute


United States: Federal Government

Study ID:

Pro00008771 (CDR0000067374)



Start Date:

September 1999

Completion Date:

June 2009

Related Keywords:

  • Sickle Cell Anemia
  • Severe Aplastic Anemia
  • Paroxysmal Nocturnal Hemoglobinuria (PNH)
  • Pure Red Cell Aplasia
  • sickle cell anemia
  • severe aplastic anemia
  • Anemia
  • Anemia, Aplastic
  • Anemia, Sickle Cell
  • Hemoglobinopathies
  • Hemoglobinuria
  • Hemoglobinuria, Paroxysmal
  • Pancytopenia
  • Red-Cell Aplasia, Pure



Florida Hospital Cancer Institute Orlando, Florida  32804
Duke Cancer Institute Durham, North Carolina  27710