Allogeneic Mixed Chimerism Stem Cell Transplant Using Campath for Hemoglobinopathies & Bone Marrow Failure Syndromes

NCT00004143 | Completed Phase 2 Results DMC

• 4 other identifiers: Pro00008771DUMC-1340-99-7NCI-G99-1617CDR0000067374
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Although used primarily to treat malignant disorders of the blood, allogeneic stem cell transplantation can also cure a variety of non-cancerous, inherited or acquired disorders of the blood. Unfortunately, the conventional approach to allogeneic stem cell transplantation is a risky procedure. For some non-cancerous conditions, the risks of this procedure outweigh the potential benefits. This protocol is designed to test a new approach to allogeneic stem cell transplantation. It is hoped that this approach will be better suited for patients with non-cancerous blood and bone marrow disorders.

Conditions

Sickle Cell Anemia; Severe Aplastic Anemia; Paroxysmal Nocturnal Hemoglobinuria (PNH); Pure Red Cell Aplasia

Keywords

sickle cell anemia; severe aplastic anemia

Outcome Measures

Primary Outcomes (5)

• Number of Patients With Neutrophil Engraftment

  Number of patients with neutrophil engraftment: Absolute Neutrophil Count (ANC) \> 500/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).

  1 year post transplant

• Number of Patients With Platelet Engraftment

  Number of patients with platelet engraftment - 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).

  1 year post transplant

• Number of Patients With Grade 3-4 Acute Graft Versus Host Disease (GVHD)

  Number of patients with Grade 3-4 acute Graft Versus Host Disease (GVHD). GVHD will be monitored at least two times per week through day 45, then weekly through day 60 and graded by 2 persons at each institution, to ensure internal consistency in grading.

  60 days post transplant

• Number of Participants With Grade 3-4 Unexpected Adverse Events

  An unexpected adverse event is one that differs in the nature, severity, or frequency from (a) the research procedures that are described in the protocol-related documents, (such as the IRB-approved research protocol and informed consent document) as expected, and/or (b) the characteristics of the subject population being studied.

  45 days post transplant

• Number of Participants With Transplant-related Mortality

  Number of patients who died due to transplant-related complications

  100 days

Secondary Outcomes (1)

• Overall Survival

  2 years

Study Arms (2)

Campath SCT for hemoglobinopathies

EXPERIMENTAL

Campath, Chemo and/or TBI Allo SCT

Drug: Campath, Chemo and/or TBI Allo SCT

Campath SCT for Bone Marrow Failure

EXPERIMENTAL

Campath, Chemo and/or TBI Allo SCT

Drug: Campath, Chemo and/or TBI Allo SCT

Interventions

Campath, Chemo and/or TBI Allo SCT DRUG

Allogeneic PBSC/marrow will be collected/harvested from the donor after granulocyte colony-stimulating factor (G-CSF) priming. The allogeneic PBSCs will be infused as per current institutional practice.

Also known as: Alemtuzumab, Allogeneic Hematopoietic Stem Cell Transplant

Campath SCT for Bone Marrow Failure; Campath SCT for hemoglobinopathies

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 meet the following laboratory parameters unless due to disease status as determined by the treating physician:
• bilirubin and hepatic transaminases and creatinine must be reviewed by the transplantation center and deemed acceptable.
• HIV antibody negative.
• 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 transplant.
• 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
• 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.
• Paroxysmal nocturnal hemoglobinuria (PNH): Patients must have a history of either life-threatening thrombosis, cytopenia, transfusion dependence or recurrent, debilitating hemolytic crisis

You may not qualify if:

• 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

Sponsors & Collaborators

• David Rizzieri, MD: lead

Study Sites (2)

Florida Hospital Cancer Institute

Orlando, Florida, 32804, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Anemia, Aplastic; Hemoglobinuria, Paroxysmal; Red-Cell Aplasia, Pure

Interventions

Alemtuzumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bone Marrow Failure Disorders; Bone Marrow Diseases; Myelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Small number of subjects analyzed

Results Point of Contact

• Title: Mitchell Horwitz, MD
• Organization: Duke University Medical Center

Mitchell.Horwitz@duke.edu

919-668-1045

Study Officials

• David A. Rizzieri, MD

  Duke Cancer Institute

  STUDY CHAIR

• Mitchell Horwitz, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 10, 1999
• First Posted: January 27, 2003
• Study Start: September 1, 1999
• Primary Completion: May 1, 2008
• Study Completion: June 1, 2009
• Last Updated: December 5, 2014
• Results First Posted: November 11, 2013

Record last verified: 2014-11

Locations

US (2)