Myelodysplastic SyndromesPhase 2NCT00593645
Clofarabine, Cytarabine, and Thymoglobulin for Allogeneic Transplantation
A Phase 2 study testing Clofarabine, Cytarabine and Thymoglobulin in people with Myelodysplastic Syndromes and Acute Myeloid Leukemia, run by Washington University School of Medicine at 1 site in United States.
Trial summary
This study will test the combination of clofarabine, cytarabine, and thymoglobulin as a non-myeloablative conditioning regimen for patients with myelodysplastic syndromes or acute myeloid leukemia undergoing allogeneic stem cell transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Acute Myeloid Leukemia
- What is being tested?
- Clofarabine, Cytarabine and Thymoglobulin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Jul 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
- Myelodysplastic Syndrome (MDS), as defined by the World Health Organization criteria, OR Chronic Myelomonocytic Leukemia (CMML) as defined by the French American British classification OR Acute Myeloid Leukemia (AML) in complete remission [excluding FAB-M3] diagnosed by standard criteria and meet the criteria below:
- Patients may be in any CR
- No more than 2 cycles of consolidation. Any consolidation regimen may be used.
- No more than 6 months from documented CR to transplant.
- Age 18 years or older.
- ECOG performance status <=2
Show all 20Show fewer
- Identification of suitable donor
- DLCO >=40% with no symptomatic pulmonary disease
- LVEF by MUGA >= 30%
- Serum creatinine <=1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black).
- Bilirubin <=2 times the upper limit of normal
- AST <=3 times the upper limit of normal
- Donor criteria:
- HLA-Matched Sibling: The donor must be an adequate HLA match as determined by serologic typing for class (A, B) and low resolution molecular typing for class II (DRB1) as defined by institutional standards.
- Matched Unrelated Donor: An acceptable match per NMDP standards based on high resolution molecular typing.
- The donor must be healthy and must be an acceptable donor as per institutional standards for stem cell collection.
- The donor must have no significant cardiopulmonary, renal, endocrine, or hepatic disease.
- There is no upper age restriction for donors, but they must be at least 18 years of age.
- Syngeneic donors are not eligible.
- No known HIV.
Who cannot join
- Pregnant or nursing.
- Active systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment.
- Severe concurrent disease, including severe insulin-dependent diabetes, uncontrolled hypertension, transient ischemic attacks, uncontrolled symptomatic coronary artery disease, or symptomatic CNS involvement or psychiatric illness/social situations that would limit compliance with study requirements.
- Known HIV disease.
- History of other malignancy except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast unless the subject has been off treatment and free from disease for > 3 years.
- Active disease at the time of transplant.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Non-Myeloablative Conditioning Regimen for Allogeneic Transplantation With Clofarabine, Cytarabine, and Thymoglobulin for Myelodysplastic Syndrome and Acute Myeloid Leukemia
This study will test the combination of clofarabine, cytarabine, and thymoglobulin as a non-myeloablative conditioning regimen for patients with myelodysplastic syndromes or acute myeloid leukemia undergoing allogeneic stem cell transplant.
Read the detailed description
Current reduced intensity conditioning regimens have been able to decrease TRM (treatment related mortality) but suffer from increased rates of disease relapse. Disease burden at transplantation, as measured by percent myeloblasts, predicts relapse. Current regimens employ fludarabine and busulfan with various adjutants, but these agents are not part of the usual armamentarium used versus leukemia and have questionable anti-leukemic activity. By substituting clofarabine and cytarabine, a combination with proven anti-leukemic activity in the relapsed and refractory setting as well as activity versus MDS, as the back bone of the regimen we hope overcome residual disease and improve post-transplant relapse rates. Furthermore the principal toxicity of this regimen is myelosuppression, which should be abrogated by the infusion of stem cells. Thymoglobulin is included due to its minimal contribution to toxicity but significant benefits in engraftment, and controlling acute and chronic GVHD, which are major contributors to TRM and disease specific activity in MDS.
- Conditions
- Myelodysplastic Syndromes, Acute Myeloid Leukemia
- Being tested
- Clofarabine, Cytarabine, Thymoglobulin, Stem cell infusion
- Keywords
- Conditioning regimens, Stem Cell Transplantation, Hematopoietic Stem Cell Transplantation, Allogeneic Stem Cell Transplantation, Nonmyeloablative conditioning, Clofarabine, Cytarabine, Anti-thymocyte globulin
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClofarabineDrug
Also called Clolar
CytarabineDrug
Also called Ara-C, Cytosar
ThymoglobulinDrug
Also called Anti-thymocyte globulin
Stem cell infusionProcedure or surgery
Also called Stem cell transplant, Hematopoietic stem cell transplant, Peripheral blood stem cell transplant, Bone marrow transplant
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Non-myeloablative conditioning regimen | Experimental | * Clofarabine 40mg/m2/day IV over two hours daily x 5 days on Days -6 thru -2
* Cytarabine 1gm/m2/day IV over two hours daily x 5 days on Days -6 thru -2 after the START of Clofarabine.
* Thymoglobulin 1.0mg/kg IV over 6 hours X 1 day on Day -4, then 2.5mg/kg/day x 2 days on Days -3 and -2.
* Stem Cell Transplant - On day 0 a minimum of total CD34+ cell dose of 2 x10E6/kg (actual weight of recipient) will be infused. Receives: Drug: Clofarabine; Drug: Cytarabine; Drug: Thymoglobulin; Procedure: Stem cell infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Six-month Treatment Related Mortality
Measured: 6 months
Secondary outcomes (10)
Disease Specific Response Rates
Disease-specific partial response and complete response.
Measured: One, three, six and twelve months.
Engraftment as Measured by Percent Donor Chimerism
Measured: Day +30
Engraftment as Measured by Percent Donor Chimerism
Measured: Day +40-+60
Engraftment as Measured by Percent Donor Chimerism
Measured: Day +80-+90
Overall Survival
Measured: 5 years from time of restaging
Disease-free Survival
Disease-free survival is defined as the length of time after treatment ends that the participant survives without any signs or symptoms of that cancer.
Measured: 5 years from time of restaging
Rate of Acute Graft-versus-host Disease (GVHD)
Acute GVHD occurs within 100 days of transplant.
Measured: Up to 100 days after transplant
Rate of Chronic Graft-versus-host Disease (GVHD)
Measured: 100 days-1 year after transplant
Use Conventional STR-PCR Method for Monitoring Engraftment
Includes assessment of mixed chimerism in the whole blood, myeloid cells, T cells, and B cells.
Measured: Up to 1 year after transplant
Median Time to Progression
Time to progression is defined as the length of time from the start of treatment until the disease starts to get worse or spread to other parts of the body.
Measured: 5 years from time of restaging
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2008 (estimated)
- Study startNov 2007
- Primary completionDec 2008
- Study completionJul 2009
Why it stopped: toxicities were worse than expected
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 Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ravi Vij, M.D., Principal investigator, Washington Universtiy of St. Louis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00593645
- Sponsor's protocol ID
- 07-0702
- Other IDs
- No grant number
- Status last verified
- Sep 2014
- First submitted
- 2 Jan 2008
- Last updated
- 12 Sep 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 12 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-Myeloablative Conditioning Regimen for Allogeneic Transplantation With Clofarabine, Cytarabine, and Thymoglobulin for Myelodysplastic Syndrome and Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT00593645
- Acronym / sponsor ID
- 07-0702
- Conditions
- Myelodysplastic Syndromes, Acute Myeloid Leukemia
- Keywords
- Conditioning regimens, Stem Cell Transplantation, Hematopoietic Stem Cell Transplantation, Allogeneic Stem Cell Transplantation, Nonmyeloablative conditioning, Clofarabine, Cytarabine, Anti-thymocyte globulin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: toxicities were worse than expected
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Nov 2007
- Primary completion
- Dec 2008 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 15 Jan 2008 (estimated)
- Results
- Posted 12 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test the combination of clofarabine, cytarabine, and thymoglobulin as a non-myeloablative conditioning regimen for patients with myelodysplastic syndromes or acute myeloid leukemia undergoing allogeneic stem cell transplant.
Detailed description
Current reduced intensity conditioning regimens have been able to decrease TRM (treatment related mortality) but suffer from increased rates of disease relapse. Disease burden at transplantation, as measured by percent myeloblasts, predicts relapse. Current regimens employ fludarabine and busulfan with various adjutants, but these agents are not part of the usual armamentarium used versus leukemia and have questionable anti-leukemic activity. By substituting clofarabine and cytarabine, a combination with proven anti-leukemic activity in the relapsed and refractory setting as well as activity versus MDS, as the back bone of the regimen we hope overcome residual disease and improve post-transplant relapse rates. Furthermore the principal toxicity of this regimen is myelosuppression, which should be abrogated by the infusion of stem cells. Thymoglobulin is included due to its minimal contribution to toxicity but significant benefits in engraftment, and controlling acute and chronic GVHD, which are major contributors to TRM and disease specific activity in MDS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Non-myeloablative conditioning regimen | Experimental | Drug: Clofarabine, Drug: Cytarabine, Drug: Thymoglobulin, Procedure: Stem cell infusion* Clofarabine 40mg/m2/day IV over two hours daily x 5 days on Days -6 thru -2 * Cytarabine 1gm/m2/day IV over two hours daily x 5 days on Days -6 thru -2 after the START of Clofarabine. * Thymoglobulin 1.0mg/kg IV over 6 hours X 1 day on Day -4, then 2.5mg/kg/day x 2 days on Days -3 and -2. * Stem Cell Transplant - On day 0 a minimum of total CD34+ cell dose of 2 x10E6/kg (actual weight of recipient) will be infused. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Myelodysplastic Syndrome (MDS), as defined by the World Health Organization criteria, OR Chronic Myelomonocytic Leukemia (CMML) as defined by the French American British classification OR Acute Myeloid Leukemia (AML) in complete remission [excluding FAB-M3] diagnosed by standard criteria and meet the criteria below:
- Age 18 years or older.
- ECOG performance status <=2
- Identification of suitable donor
- DLCO >=40% with no symptomatic pulmonary disease
Key exclusion criteria (6 listed)
- Pregnant or nursing.
- Active systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment.
- Severe concurrent disease, including severe insulin-dependent diabetes, uncontrolled hypertension, transient ischemic attacks, uncontrolled symptomatic coronary artery disease, or symptomatic CNS involvement or psychiatric illness/social situations that would limit compliance with study requirements.
- Known HIV disease.
- History of other malignancy except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast unless the subject has been off treatment and free from disease for > 3 years.
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 |
|---|---|---|
| ClofarabineAlso: Clolar | Drug | Arm 1: Non-myeloablative conditioning regimen |
| CytarabineAlso: Ara-C, Cytosar | Drug | Arm 1: Non-myeloablative conditioning regimen |
| ThymoglobulinAlso: Anti-thymocyte globulin | Drug | Arm 1: Non-myeloablative conditioning regimen |
| Stem cell infusionAlso: Stem cell transplant, Hematopoietic stem cell transplant, Peripheral blood stem cell transplant, Bone marrow transplant | Procedure or surgery | Arm 1: Non-myeloablative conditioning regimen |
Primary outcome
Six-month Treatment Related Mortality
Time frame: 6 months
10 secondary outcomes
Disease Specific Response Rates
Time frame: One, three, six and twelve months.
Engraftment as Measured by Percent Donor Chimerism
Time frame: Day +30
Engraftment as Measured by Percent Donor Chimerism
Time frame: Day +40-+60
Engraftment as Measured by Percent Donor Chimerism
Time frame: Day +80-+90
Overall Survival
Time frame: 5 years from time of restaging
Disease-free Survival
Time frame: 5 years from time of restaging
Rate of Acute Graft-versus-host Disease (GVHD)
Time frame: Up to 100 days after transplant
Rate of Chronic Graft-versus-host Disease (GVHD)
Time frame: 100 days-1 year after transplant
Use Conventional STR-PCR Method for Monitoring Engraftment
Time frame: Up to 1 year after transplant
Median Time to Progression
Time frame: 5 years from time of restaging
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
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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.
Ravi Vij, M.D. principal investigator
Washington Universtiy of St. Louis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Clofarabine, Cytarabine and Thymoglobulin in people with Myelodysplastic Syndromes and Acute Myeloid Leukemia, run by Washington University School of Medicine at 1 site 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 20 inclusion and 6 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: stopped early, as of the sponsor's last update on 12 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 12 Sep 2014). 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?
Six-month Treatment Related Mortality (time frame: 6 months). 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 12 Sep 2014; AzTrials last refreshed its copy on 8 Nov 2026.