Aplastic AnemiaPhase 2NCT00343785
Cyclophosphamide and Anti-thymocyte Globulin Followed By Methotrexate and Cyclosporine in Preventing Chronic Graft-Versus-Host Disease in Patients With Severe Aplastic Anemia Undergoing Donor Bone Marrow Transplant
A Phase 2 study testing cyclophosphamide, anti-thymocyte globulin and cyclosporine in people with Aplastic Anemia, run by Fred Hutchinson Cancer Center at 3 sites in United States.
Trial summary
This clinical trial is studying how well giving cyclophosphamide together with anti-thymocyte globulin followed by methotrexate and cyclosporine works in preventing chronic graft-vs-host disease (GVHD) in patients with severe aplastic anemia undergoing donor bone marrow transplant. Read more about this study
- Who is it for?
- Ages Up to 65 years
- Conditions the study is for
- Aplastic Anemia
- What is being tested?
- cyclophosphamide, anti-thymocyte globulin and cyclosporine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2006to Aug 2012
- 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 Up to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Any patient who has aplastic anemia with marrow failure involving 2 of the three following criteria: granulocytes < 500/uL; a corrected reticulocyte count of < 1%; platelet count of < 20,000/uL
- Availability of an human leukocyte antigen (HLA)-matched family member
- DONOR: Family member who is HLA-matched
- DONOR: If more than one HLA-matched family member is available, priority will be given to a donor who is genotypically HLA-identical, of appropriate cytomegalovirus (CMV) serology, ABO compatible, and, in case of a female donor, non-parous
Who cannot join
- Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure:
- Patients who have developed clonal cytogenetic abnormalities or myelodysplastic syndrome (preleukemia)
- Patients with Fanconi's anemia
- Aplasia secondary to radiation or cytotoxic chemotherapy
- Patients with paroxysmal nocturnal hemoglobinuria who have not developed aplastic anemia
- Severe organ toxicities:
Show all 14Show fewer
- Cardiac insufficiency requiring treatment or symptomatic coronary artery disease;
- Severe hypoxemia , partial pressure of oxygen (pO2) < 70 mm Hg, with decreased diffusion capacity of carbon monoxide (DLCO) < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted;
- Impaired renal function (creatinine > 2 times upper limit of normal or estimated creatinine clearance < 60 ml/min)
- Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
- Human immunodeficiency virus (HIV)-positive patients
- Females who are pregnant or breast-feeding
- DONOR: Donors who have increase anesthetic risk and are not able psychologically and medically to tolerate the procedure
- DONOR: HIV-positive donors
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: Cyclophosphamide and Antithymocyte Globulin Conditioning Regimen for Marrow Transplantation From HLA-Matched Family Members for Severe Aplastic Anemia: Effect of Marrow Cell Dose on Chronic Graft-vs.-Host Disease: A Multi-Center Trial
This clinical trial is studying how well giving cyclophosphamide together with anti-thymocyte globulin followed by methotrexate and cyclosporine works in preventing chronic graft-vs-host disease (GVHD) in patients with severe aplastic anemia undergoing donor bone marrow transplant. Giving low doses of chemotherapy, such as cyclophosphamide, before a donor bone marrow transplant helps stop the growth of abnormal cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining abnormal cells. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving anti-thymocyte globulin before and methotrexate and cyclosporine after transplant may stop this from happening
Read the detailed description
PRIMARY OBJECTIVES:
- Minimize the incidence of chronic GVHD by restricting the transplanted marrow dose to 2.0-2.5 x 10^8 nucleated cells/kg.
SECONDARY OBJECTIVES:
- Engraftment and overall survival.
OUTLINE:
CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) on days -5 to -2 and anti-thymocyte globulin IV over 4-10 hours on days -4 to -2.
TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0.
GVHD PROPHYLAXIS: Patients receive methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or orally (PO) twice daily on days -1 to 50, followed by a taper until 6 months after grafting.
After completion of study treatment, patients are followed up at on day 180, 1 year, 1.5 years, 2 years, 3 years, and yearly thereafter.
- Conditions
- Aplastic Anemia
- Being tested
- cyclophosphamide, anti-thymocyte globulin, cyclosporine, allogeneic bone marrow transplantation, methotrexate
- Medical subject headings
- Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclophosphamideDrug
Also called CPM, CTX, Cytoxan, Endoxan
Given IV
anti-thymocyte globulinBiological
Also called ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin
Given IV
cyclosporineDrug
Also called ciclosporin, cyclosporin, cyclosporin A, CYSP
Given IV or PO
allogeneic bone marrow transplantationProcedure or surgery
Also called bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow
Undergo allogeneic bone marrow transplantation
methotrexateDrug
Also called amethopterin, Folex, methylaminopterin, Mexate
Given IV
DNA analysisGenetic
Correlative studies
flow cytometryOther
Correlative studies
polymorphism analysisGenetic
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (conditioning regimen, transplant, GVHD prophylaxis) | Experimental | Patients receive a conditioning regimen comprising cyclophosphamide IV on days -5 to -2 and anti-thymocyte globulin IV over 4-10 hours on days -4 to -2. Patients undergo allogeneic bone marrow transplantation on day 0. Patients then receive GVHD prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or PO twice daily on days -1 to 50, followed by a taper until 6 months after grafting. Receives: Drug: cyclophosphamide; Biological: anti-thymocyte globulin; Drug: cyclosporine; Procedure: allogeneic bone marrow transplantation; Drug: methotrexate; Genetic: DNA analysis; Other: flow cytometry; Genetic: polymorphism analysis; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Chronic GVHD
Analyzed using cumulative incidence estimates, treating death or rejection as competing risk events.
Measured: 2 years
Secondary outcomes (2)
Number of Days to Neutrophil Recovery to >500/uL
First of 3 consecutive days of neutrophils >500/uL
Measured: 100 days post-transplant
Overall Survival
Number of patients alive at one year
Measured: From the time of enrollment until death from any cause up to one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2006 (estimated)
- Study startFeb 2006
- Primary completionMay 2012
- Study completionAug 2012
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 Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Rainer Storb, Fred Hutchinson Cancer Center
- Investigators
- Rainer Storb, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00343785
- Sponsor's protocol ID
- 2054.00
- Other IDs
- NCI-2010-01781, P01HL036444
- Status last verified
- Mar 2017
- First submitted
- 22 Jun 2006
- Last updated
- 13 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cyclophosphamide and Antithymocyte Globulin Conditioning Regimen for Marrow Transplantation From HLA-Matched Family Members for Severe Aplastic Anemia: Effect of Marrow Cell Dose on Chronic Graft-vs.-Host Disease: A Multi-Center Trial
- ClinicalTrials.gov ID
- NCT00343785
- Acronym / sponsor ID
- 2054.00
- Conditions
- Aplastic Anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Feb 2006
- Primary completion
- May 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 23 Jun 2006 (estimated)
- Results
- Posted 16 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial is studying how well giving cyclophosphamide together with anti-thymocyte globulin followed by methotrexate and cyclosporine works in preventing chronic graft-vs-host disease (GVHD) in patients with severe aplastic anemia undergoing donor bone marrow transplant. Giving low doses of chemotherapy, such as cyclophosphamide, before a donor bone marrow transplant helps stop the growth of abnormal cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining abnormal cells. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving anti-thymocyte globulin before and methotrexate and cyclosporine after transplant may stop this from happening
Detailed description
PRIMARY OBJECTIVES:
- Minimize the incidence of chronic GVHD by restricting the transplanted marrow dose to 2.0-2.5 x 10^8 nucleated cells/kg.
SECONDARY OBJECTIVES:
- Engraftment and overall survival.
OUTLINE:
CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) on days -5 to -2 and anti-thymocyte globulin IV over 4-10 hours on days -4 to -2.
TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0.
GVHD PROPHYLAXIS: Patients receive methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or orally (PO) twice daily on days -1 to 50, followed by a taper until 6 months after grafting.
After completion of study treatment, patients are followed up at on day 180, 1 year, 1.5 years, 2 years, 3 years, and yearly thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (conditioning regimen, transplant, GVHD prophylaxis) | Experimental | Drug: cyclophosphamide, Biological: anti-thymocyte globulin, Drug: cyclosporine, Procedure: allogeneic bone marrow transplantation, Drug: methotrexate, Genetic: DNA analysis, Other: flow cytometry, Genetic: polymorphism analysis, Other: laboratory biomarker analysisPatients receive a conditioning regimen comprising cyclophosphamide IV on days -5 to -2 and anti-thymocyte globulin IV over 4-10 hours on days -4 to -2. Patients undergo allogeneic bone marrow transplantation on day 0. Patients then receive GVHD prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or PO twice daily on days -1 to 50, followed by a taper until 6 months after grafting. |
Who may qualify
- Ages
- Up to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Any patient who has aplastic anemia with marrow failure involving 2 of the three following criteria: granulocytes < 500/uL; a corrected reticulocyte count of < 1%; platelet count of < 20,000/uL
- Availability of an human leukocyte antigen (HLA)-matched family member
- DONOR: Family member who is HLA-matched
- DONOR: If more than one HLA-matched family member is available, priority will be given to a donor who is genotypically HLA-identical, of appropriate cytomegalovirus (CMV) serology, ABO compatible, and, in case of a female donor, non-parous
Key exclusion criteria (14 listed)
- Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure:
- Severe organ toxicities:
- Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
- Human immunodeficiency virus (HIV)-positive patients
- Females who are pregnant or breast-feeding
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 |
|---|---|---|
| cyclophosphamideAlso: CPM, CTX, Cytoxan, EndoxanGiven IV | Drug | Treatment (conditioning regimen, transplant, GVHD prophylaxis) |
| anti-thymocyte globulinAlso: ATG, ATGAM, lymphocyte immune globulin, ThymoglobulinGiven IV | Biological | Treatment (conditioning regimen, transplant, GVHD prophylaxis) |
| cyclosporineAlso: ciclosporin, cyclosporin, cyclosporin A, CYSPGiven IV or PO | Drug | Treatment (conditioning regimen, transplant, GVHD prophylaxis) |
| allogeneic bone marrow transplantationAlso: bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrowUndergo allogeneic bone marrow transplantation | Procedure or surgery | Treatment (conditioning regimen, transplant, GVHD prophylaxis) |
| methotrexateAlso: amethopterin, Folex, methylaminopterin, MexateGiven IV | Drug | Treatment (conditioning regimen, transplant, GVHD prophylaxis) |
| DNA analysisCorrelative studies | Genetic | Treatment (conditioning regimen, transplant, GVHD prophylaxis) |
| flow cytometryCorrelative studies | Other | Treatment (conditioning regimen, transplant, GVHD prophylaxis) |
| polymorphism analysisCorrelative studies | Genetic | Treatment (conditioning regimen, transplant, GVHD prophylaxis) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (conditioning regimen, transplant, GVHD prophylaxis) |
Primary outcome
Incidence of Chronic GVHD
Time frame: 2 years
Analyzed using cumulative incidence estimates, treating death or rejection as competing risk events.
2 secondary outcomes
Number of Days to Neutrophil Recovery to >500/uL
Time frame: 100 days post-transplant
Overall Survival
Time frame: From the time of enrollment until death from any cause up to one year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2017.
- 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.
Rainer Storb principal investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
3 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 cyclophosphamide, anti-thymocyte globulin and cyclosporine in people with Aplastic Anemia, run by Fred Hutchinson Cancer Center at 3 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 4 inclusion and 14 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 13 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 16 Mar 2017). 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?
Incidence of Chronic GVHD (time frame: 2 years). 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 13 Apr 2017.