LeukemiaNCT00660400
Pre-Transplant 5-Azacitidine In Patients With High-Risk Myelodysplastic Syndrome Who Are Candidates For Allogeneic Hematopoietic Cell Transplant
A study testing 5-azacitidine and Allogeneic Hematopoietic Cell Transplantation (HCT) in people with Leukemia, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The purpose of this study is to find out if treating people who have high-risk myelodysplastic syndrome (MDS) with 5-Azacitidine (Vidaza) prior to their allogeneic hematopoietic cell transplant (HCT) is helpful in preventing their myelodysplastic syndrome from coming back. Read more about this study
- Who is it for?
- Ages 18 to 68 years
- Conditions the study is for
- Leukemia
- What is being tested?
- 5-azacitidine and Allogeneic Hematopoietic Cell Transplantation (HCT)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2008to Jun 2014
- Phase
- Interventional
- 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 to 68 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Potential candidate for HCT.
- Histologically confirmed diagnosis by pathologic review of previous diagnosis of high-risk myelodysplastic syndrome (MDS): International Prognostic Scoring System (IPSS) > 1 or AML-MDS or treatment related MDS.
- Serum bilirubin levels ≤1.5 times the upper limit of the normal (ULN) range for the laboratory. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis; Serum glutamic-oxaloacetic transaminase (SGOT) [aspartate aminotransferase (AST)] or serum glutamic pyruvic transaminase (SGPT) [alanine aminotransferase (ALT)] levels ≤2 x ULN.
- Serum creatinine levels ≤1.5 x ULN
- Karnofsky performance status greater or equal to 70%
- Signed informed consent form in accordance with institutional policies
Who cannot join
- Known or suspected hypersensitivity to Vidaza or mannitol
- Pregnant or lactating women
- Human immunodeficiency virus (HIV) or seropositive, confirmed by nucleic acid amplification testing (NAT)
- Active central nervous system (CNS) malignancy
- Active infection
- History or presence of primary hepatoma
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
About this study
Official title: A Pilot Study Of Pre-Transplant 5-Azacitidine (Vidaza) In Patients With High-Risk Myelodysplastic Syndrome (MDS) Who Are Candidates For Allogeneic Hematopoietic Cell Transplantation
The purpose of this study is to find out if treating people who have high-risk myelodysplastic syndrome (MDS) with 5-Azacitidine (Vidaza) prior to their allogeneic hematopoietic cell transplant (HCT) is helpful in preventing their myelodysplastic syndrome from coming back.
In previous research, 5-Azacitidine appeared to help the bone marrow of a patient with MDS begin to function more normally. This means bone marrow cells can grow and do their work the way they were meant to. 5-Azacitidine is approved by the Food and Drug Administration (FDA) for the treatment of MDS. The effect of 5-Azacitidine in patients receiving hematopoietic cell transplants have not been studied.
Read the detailed description
RESEARCH PLAN
- This will be a single-center prospective trial
- Patients with high risk MDS that are potentially eligible for HCT will be enrolled.
- A donor search will be initiated, and 5-Azacitidine will be given per standard practice.
- 5-Azacitidine dose is 75 mg/M^2/day subcutaneously by standard practice (generally this is 7 days per monthly cycle, but alterations occur depending on clinical and laboratory parameters).
- Patients where a suitable donor is not found can continue with 5-Azacitidine per standard treatment. These patients will be followed until progression of MDS to acute myelogenous leukemia (AML) or death, for up to one year.
- If a suitable donor is obtained, the patient will proceed to HCT. The HCT conditioning regimen will be dictated by the Blood and Marrow Transplant (BMT) physician. While waiting HCT, additional cycles 5-Azacitidine may be given. Pre-HCT conditioning regimen therapy will begin no more than 8 weeks and no less than 4 weeks after the last administration of 5-Azacitidine.
- As the number of cycles of 5-Azacitidine is not standardized and the retrospective review of our patients noted above indicated a benefit to ANY exposure to 5-Azacitidine, the actual number of cycles of 5-Azacitidine delivered will not be specified. In addition, as high risk MDS patients have an average time to death of 0.4 years, any delay to HCT once it is available is to be avoided.
- A bone marrow biopsy will be performed to reassess disease response to therapy after the last cycle of 5-Azacitidine before transplant, or after the fourth cycle of 5-Azacitidine, whichever comes first. Note that both the biopsy and the timing of the biopsy is a standard evaluation procedure.
- Donor progenitor cell collection will be prescribed by the BMT Attending Physician.
HCT
- The patient will undergo HCT designated per attending BMT physician.
- Supportive care will be based on institutional guidelines, Stem cell collections, processing and laboratory studies
Stem cell collections, processing and laboratory studies
- Graft assessment, processing, and characterization will be done as per institutional guidelines
- Chimerism testing will be obtained to document post-transplant engraftment, per standard practice.
- Conditions
- Leukemia
- Being tested
- 5-azacitidine, Allogeneic Hematopoietic Cell Transplantation (HCT)
- Keywords
- Myeloid, Monocytic
- Medical subject headings
- Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-azacitidineDrug
Also called Vidaza
Once enrolled, the patients will receive pre-transplant 5-azacitidine (Vidaza) 75 mg/M^2/day subcutaneously for 5-7 days every 28 days). Adjustments in dose and timing may occur based on clinical and hematological parameters.
Allogeneic Hematopoietic Cell Transplantation (HCT)Procedure or surgery
Also called HCT
Patients will receive transplantation if there is either a suitable sibling or an unrelated donor.
- Response will be evaluated by bone marrow biopsy after 4 cycles of 5-azacitidine or prior to HCT whichever comes first. Due to the very high risk of progression to AML or death in this patient population, the HCT will be done as soon as possible.
- The patients may have additional cycles of 5-azacitidine per standard hematology practice until scheduled for transplant or until progression of disease.
- All patients will be followed until time to progression of MDS, AML or death or a maximum of 1 year. For patients that are transplanted, follow up will be to one year post-transplant.
| Study group | Role | What they receive |
|---|---|---|
| Combined Therapy | Experimental | 5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT). Receives: Drug: 5-azacitidine; Procedure: Allogeneic Hematopoietic Cell Transplantation (HCT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Relapse-free Survival (RFS)
Relapse-free survival one year after allogeneic HCT in MDS patients receiving at least one complete cycle of 5-azacitidine (Vidaza) in the pre-transplantation setting. Relapsed disease: if with complete remission (CR) - greater than 5% blasts in bone marrow; if with partial response (PR) - greater than 30% increase in blasts in the marrow; if with stable disease (SD) - return to pretreatment peripheral blood levels and transfusion requirements due to disease.
Measured: One year post allogeneic HCT
Secondary outcomes (3)
Overall Response Rate (ORR)
Pre-allogeneic HCT responses to 5-azacitidine (Vidaza), based on the International Working Group criteria: Complete Remission (CR); Partial Response (PR); Stable Disease (SD). Point estimates and 95% confidence intervals were calculated for the response rate to 5-azacitidine, evaluated at marrow evaluation after 4 cycles of 5-azacitidine or prior to HCT whichever came first. CR: Bone marrow with 5% myeloblasts and normal maturation of all cell lines. PR: All CR criteria if abnormal before treatment except bone marrow blasts decreased by 50% over pretreatment but still > 5%. SD: Failure to attain CR, PR, relapsed (or progressive) disease.
Measured: At the end of up to six (28 day) cycles of 5-azacitidine
Percentage of Participants Who Proceed to Hematopoietic Cell Transplantation (HCT)
Proportion of patients enrolled who subsequently proceeded to allogeneic HCT.
Measured: Up to 3 years
Percentage of Participants With Overall Survival (OS)
Overall survival for all participants at one year after first dose of 5-azacitidine (Vidaza). Overall survival was calculated by the method of Kaplan-Meier with standard errors computed using Greenwood's formula.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2008 (estimated)
- Study startMar 2008
- Primary completionDec 2013
- Study completionJun 2014
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- Teresa Field, M.D., Ph.D., Principal investigator, H. Lee Moffitt Cancer Center and Research InstituteJanelle Perkins, Pharm.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00660400
- Sponsor's protocol ID
- MCC-15158
- Other IDs
- 106349
- Status last verified
- Sep 2014
- First submitted
- 16 Apr 2008
- Last updated
- 22 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Nishihori T, Perkins J, Mishra A, Komrokji R, Kim J, Kharfan-Dabaja MA, Perez L, Lancet J, Fernandez H, List A, Anasetti C, Field T. Pretransplantation 5-azacitidine in high-risk myelodysplastic syndrome. Biol Blood Marrow Transplant. 2014 Jun;20(6):776-80. doi: 10.1016/j.bbmt.2014.02.008. Epub 2014 Feb 15.
PubMed 24534108
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Of Pre-Transplant 5-Azacitidine (Vidaza) In Patients With High-Risk Myelodysplastic Syndrome (MDS) Who Are Candidates For Allogeneic Hematopoietic Cell Transplantation
- ClinicalTrials.gov ID
- NCT00660400
- Acronym / sponsor ID
- MCC-15158
- Conditions
- Leukemia
- Keywords
- Myeloid, Monocytic
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- Mar 2008
- Primary completion
- Dec 2013 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 17 Apr 2008 (estimated)
- Results
- Posted 16 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out if treating people who have high-risk myelodysplastic syndrome (MDS) with 5-Azacitidine (Vidaza) prior to their allogeneic hematopoietic cell transplant (HCT) is helpful in preventing their myelodysplastic syndrome from coming back.
In previous research, 5-Azacitidine appeared to help the bone marrow of a patient with MDS begin to function more normally. This means bone marrow cells can grow and do their work the way they were meant to. 5-Azacitidine is approved by the Food and Drug Administration (FDA) for the treatment of MDS. The effect of 5-Azacitidine in patients receiving hematopoietic cell transplants have not been studied.
Detailed description
RESEARCH PLAN
- This will be a single-center prospective trial
- Patients with high risk MDS that are potentially eligible for HCT will be enrolled.
- A donor search will be initiated, and 5-Azacitidine will be given per standard practice.
- 5-Azacitidine dose is 75 mg/M^2/day subcutaneously by standard practice (generally this is 7 days per monthly cycle, but alterations occur depending on clinical and laboratory parameters).
- Patients where a suitable donor is not found can continue with 5-Azacitidine per standard treatment. These patients will be followed until progression of MDS to acute myelogenous leukemia (AML) or death, for up to one year.
- If a suitable donor is obtained, the patient will proceed to HCT. The HCT conditioning regimen will be dictated by the Blood and Marrow Transplant (BMT) physician. While waiting HCT, additional cycles 5-Azacitidine may be given. Pre-HCT conditioning regimen therapy will begin no more than 8 weeks and no less than 4 weeks after the last administration of 5-Azacitidine.
- As the number of cycles of 5-Azacitidine is not standardized and the retrospective review of our patients noted above indicated a benefit to ANY exposure to 5-Azacitidine, the actual number of cycles of 5-Azacitidine delivered will not be specified. In addition, as high risk MDS patients have an average time to death of 0.4 years, any delay to HCT once it is available is to be avoided.
- A bone marrow biopsy will be performed to reassess disease response to therapy after the last cycle of 5-Azacitidine before transplant, or after the fourth cycle of 5-Azacitidine, whichever comes first. Note that both the biopsy and the timing of the biopsy is a standard evaluation procedure.
- Donor progenitor cell collection will be prescribed by the BMT Attending Physician.
HCT
- The patient will undergo HCT designated per attending BMT physician.
- Supportive care will be based on institutional guidelines, Stem cell collections, processing and laboratory studies
Stem cell collections, processing and laboratory studies
- Graft assessment, processing, and characterization will be done as per institutional guidelines
- Chimerism testing will be obtained to document post-transplant engraftment, per standard practice.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combined Therapy | Experimental | Drug: 5-azacitidine, Procedure: Allogeneic Hematopoietic Cell Transplantation (HCT)5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT). |
Who may qualify
- Ages
- 18 to 68 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Potential candidate for HCT.
- Histologically confirmed diagnosis by pathologic review of previous diagnosis of high-risk myelodysplastic syndrome (MDS): International Prognostic Scoring System (IPSS) > 1 or AML-MDS or treatment related MDS.
- Serum bilirubin levels ≤1.5 times the upper limit of the normal (ULN) range for the laboratory. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis; Serum glutamic-oxaloacetic transaminase (SGOT) [aspartate aminotransferase (AST)] or serum glutamic pyruvic transaminase (SGPT) [alanine aminotransferase (ALT)] levels ≤2 x ULN.
- Serum creatinine levels ≤1.5 x ULN
- Karnofsky performance status greater or equal to 70%
Key exclusion criteria (6 listed)
- Known or suspected hypersensitivity to Vidaza or mannitol
- Pregnant or lactating women
- Human immunodeficiency virus (HIV) or seropositive, confirmed by nucleic acid amplification testing (NAT)
- Active central nervous system (CNS) malignancy
- Active infection
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 |
|---|---|---|
| 5-azacitidineAlso: VidazaOnce enrolled, the patients will receive pre-transplant 5-azacitidine (Vidaza) 75 mg/M^2/day subcutaneously for 5-7 days every 28 days). Adjustments in dose and timing may occur based on clinical and hematological parameters. | Drug | Combined Therapy |
| Allogeneic Hematopoietic Cell Transplantation (HCT)Also: HCTPatients will receive transplantation if there is either a suitable sibling or an unrelated donor. * Response will be evaluated by bone marrow biopsy after 4 cycles of 5-azacitidine or prior to HCT whichever comes first. Due to the very high risk of progression to AML or death in this patient population, the HCT will be done as soon as possible. * The patients may have additional cycles of 5-azacitidine per standard hematology practice until scheduled for transplant or until progression of disease. * All patients will be followed until time to progression of MDS, AML or death or a maximum of 1 year. For patients that are transplanted, follow up will be to one year post-transplant. | Procedure or surgery | Combined Therapy |
Primary outcome
Percentage of Participants With Relapse-free Survival (RFS)
Time frame: One year post allogeneic HCT
Relapse-free survival one year after allogeneic HCT in MDS patients receiving at least one complete cycle of 5-azacitidine (Vidaza) in the pre-transplantation setting. Relapsed disease: if with complete remission (CR) - greater than 5% blasts in bone marrow; if with partial response (PR) - greater than 30% increase in blasts in the marrow; if with stable disease (SD) - return to pretreatment peripheral blood levels and transfusion requirements due to disease.
3 secondary outcomes
Overall Response Rate (ORR)
Time frame: At the end of up to six (28 day) cycles of 5-azacitidine
Percentage of Participants Who Proceed to Hematopoietic Cell Transplantation (HCT)
Time frame: Up to 3 years
Percentage of Participants With Overall Survival (OS)
Time frame: One year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24534108Nishihori T, Perkins J, Mishra A, Komrokji R, Kim J, Kharfan-Dabaja MA, Perez L, Lancet J, Fernandez H, List A, Anasetti C, Field T. Pretransplantation 5-azacitidine in high-risk myelodysplastic syndrome. Biol Blood Marrow Transplant. 2014 Jun;20(6):776-80. doi: 10.1016/j.bbmt.2014.02.008. Epub 2014 Feb 15.
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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.
Teresa Field, M.D., Ph.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
Janelle Perkins, Pharm.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 5-azacitidine and Allogeneic Hematopoietic Cell Transplantation (HCT) in people with Leukemia, run by H. Lee Moffitt Cancer Center and Research Institute 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 6 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: finished, as of the sponsor's last update on 22 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jul 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?
Percentage of Participants With Relapse-free Survival (RFS) (time frame: One year post allogeneic HCT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00660400, which also lists 1 linked publication.
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 22 Sep 2014.