Sickle Cell AnemiaPhase 2NCT00004143
Allogeneic Mixed Chimerism Stem Cell Transplant Using Campath for Hemoglobinopathies & Bone Marrow Failure Syndromes
A Phase 2 study testing Campath, Chemo and/or TBI Allo SCT in people with Sickle Cell Anemia and Severe Aplastic Anemia, run by David Rizzieri, MD at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sickle Cell Anemia, Severe Aplastic Anemia, Paroxysmal Nocturnal Hemoglobinuria (PNH)
- What is being tested?
- Campath, Chemo and/or TBI Allo SCT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 1999to Jun 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- bilirubin and hepatic transaminases and creatinine must be reviewed by the transplantation center and deemed acceptable.
- HIV antibody negative.
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- 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.
- 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.
- 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.
- 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
- Pure red cell aplasia: Patients must be transfusion dependent.
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Duke Cancer Institute
Durham, North Carolina, 27710
Florida Hospital Cancer Institute
Orlando, Florida, 32804
About this study
Official title: Allogeneic Mixed Chimerism Stem Cell Transplantation Utilizing In Vivo and In Vitro Campath for Hemoglobinopathies and Bone Marrow Failure Syndromes
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.
Read the detailed description
OBJECTIVES:
Primary Objective(s):
- 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).
- 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):
- 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.
- Evaluate the recovery of immune function post engraftment with this regimen.
- Conditions
- Sickle Cell Anemia, Severe Aplastic Anemia, Paroxysmal Nocturnal Hemoglobinuria (PNH), Pure Red Cell Aplasia
- Being tested
- Campath, Chemo and/or TBI Allo SCT
- Keywords
- sickle cell anemia, severe aplastic anemia
- Medical subject headings
- Anemia, Sickle Cell, Anemia, Aplastic, Hemoglobinuria, Paroxysmal, Red-Cell Aplasia, Pure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Campath, Chemo and/or TBI Allo SCTDrug
Also called Alemtuzumab, Allogeneic Hematopoietic Stem Cell Transplant
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.
| Study group | Role | What they receive |
|---|---|---|
| Campath SCT for hemoglobinopathies | Experimental | Campath, Chemo and/or TBI Allo SCT Receives: Drug: Campath, Chemo and/or TBI Allo SCT |
| Campath SCT for Bone Marrow Failure | Experimental | Campath, Chemo and/or TBI Allo SCT Receives: Drug: Campath, Chemo and/or TBI Allo SCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 45 days post transplant
Number of Participants With Transplant-related Mortality
Number of patients who died due to transplant-related complications
Measured: 100 days
Secondary outcomes (1)
Overall Survival
Number of patients alive 2 years after transplant
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startSep 1999
- Primary completionMay 2008
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Sickle Cell AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Rizzieri, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, David Rizzieri, MD, Duke University
- Investigators
- David A. Rizzieri, MD, Study chair, Duke Cancer InstituteMitchell Horwitz, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00004143
- Sponsor's protocol ID
- Pro00008771
- Other IDs
- DUMC-1340-99-7, NCI-G99-1617, CDR0000067374
- Status last verified
- Nov 2014
- First submitted
- 10 Dec 1999
- Last updated
- 5 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Mixed Chimerism Stem Cell Transplantation Utilizing In Vivo and In Vitro Campath for Hemoglobinopathies and Bone Marrow Failure Syndromes
- ClinicalTrials.gov ID
- NCT00004143
- Acronym / sponsor ID
- Pro00008771
- Conditions
- Sickle Cell Anemia, Severe Aplastic Anemia, Paroxysmal Nocturnal Hemoglobinuria (PNH), Pure Red Cell Aplasia
- Keywords
- sickle cell anemia, severe aplastic anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- David Rizzieri, MDUniversity, hospital or other
- Study start
- Sep 1999
- Primary completion
- May 2008 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Posted 11 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary Objective(s):
- 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).
- 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):
- 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.
- Evaluate the recovery of immune function post engraftment with this regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Campath SCT for hemoglobinopathies | Experimental | Drug: Campath, Chemo and/or TBI Allo SCTCampath, Chemo and/or TBI Allo SCT |
| Campath SCT for Bone Marrow Failure | Experimental | Drug: Campath, Chemo and/or TBI Allo SCTCampath, Chemo and/or TBI Allo SCT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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:
- 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.
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Campath, Chemo and/or TBI Allo SCTAlso: Alemtuzumab, Allogeneic Hematopoietic Stem Cell TransplantAllogeneic 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. | Drug | Campath SCT for Bone Marrow Failure, Campath SCT for hemoglobinopathies |
Primary outcome
Number of Patients With Neutrophil Engraftment
Time frame: 1 year post transplant
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).
Number of Patients With Platelet Engraftment
Time frame: 1 year post transplant
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).
Number of Patients With Grade 3-4 Acute Graft Versus Host Disease (GVHD)
Time frame: 60 days post transplant
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.
Number of Participants With Grade 3-4 Unexpected Adverse Events
Time frame: 45 days post transplant
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.
Number of Participants With Transplant-related Mortality
Time frame: 100 days
Number of patients who died due to transplant-related complications
1 secondary outcome
Overall Survival
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David A. Rizzieri, MD study chair
Duke Cancer Institute
Mitchell Horwitz, MD principal investigator
Duke University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Campath, Chemo and/or TBI Allo SCT in people with Sickle Cell Anemia and Severe Aplastic Anemia, run by David Rizzieri, MD at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Neutrophil Engraftment (time frame: 1 year post transplant). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2014.