Myelodysplastic SyndromePhase 2GFM-AZA-VORNCT01748240
Addition of Vorinostat to Azacitidine in Higher Risk MDS a Phase II add-on Study in Patients With Azacitidine Failure
A Phase 2 study testing Azacitidine and oral vorinostat in people with Myelodysplastic Syndrome, run by Groupe Francophone des Myelodysplasies at 24 sites in France.
Trial summary
Azacytidine (AZA) is the current standard of care for frontline patient treated with high-risk MDS and is clinically active in all type of MDS, however, 50% of the patients will never respond. Vorinostat is an orally available HDAC inhibitor with clinical activity in MDS and proven in vitro synergy with AZA. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- Azacitidine and oral vorinostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 24 sitesFrance
- Study dates
- Mar 2013to Jul 2015
- 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 (WHO and FAB classified) including: RA, RARS, RCMD, RCMD-RS RAEB , RAEB-t and CMML with WBC < 13000/mm3)
- IPSS score 1.5 or higher (IPSS intermediate-2 and high risk categories) at the beginning of azacitidine,
- Absence of response (CR, PR, marrow CR or HI according to IWG 2006) after a minimum of 6 cycles of azacitidine single agent at 75 mg/m²/d for 7 days per cycle. Patients with a previous dose reduction of AZA may be eligible if the maximum tolerated dose was equal to or above 350mg/m2/cycle (i.e. 50 mg/m²/d for 7 days or 75mg/m2/d for 5 days).
- Age more or egal to 18 years
- ECOG performance status ≤ 2 (cf. appendix 2);
- Patient must have adequate organ function as indicated by the following laboratory values
Show all 16Show fewer
- Renal Serum creatinine or calculated creatinine clearancea < 2 mg/dl OR ≥ 60 mL/min for patients with creatinine levels > 1.5 X institutional ULN Hepatic
- Serum total bilirubin ≤ 2.5 X ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels ≥ 2 mg/dL.
- AST (SGOT) and ALT (SGPT) ≤ 2.5 times ULN Alkaline Phosphatase ≤ 5 X ULN If > 2.5 X ULN, then liver fraction should be ≤ 2.5 X ULN a Creatinine clearance should be calculated per institutional standard.
- Patient is known to not be refractory to platelet transfusions.
- Patient ineligible for allogeneic hematopoietic stem cell transplantation at the time of inclusion in the study
- Adherence to the study visit schedule;
- Women of childbearing potential must:
- Agree to use effective contraception without interruption throughout the study and for a further 3 months after the end of treatment;
- Men must: Agree to not conceive during the treatment and to use effective contraception during the treatment period (including periods of dose reduction or temporary suspension) and for a further 3 months after the end of treatment if their partner is of childbearing potential.
- Agree to learn about the procedures for preservation of sperm.
Who cannot join
- Patient had prior treatment with an HDAC inhibitor (e.g., depsipeptide or NSC-630176, MS 275, LAQ-824, PXD-101, LBH589, MGCD0103, CRA024781, etc). Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study. Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period.
- Severe infection or any other uncontrolled severe condition.
- Last dose of AZA was given more than 3 months before entering the trial.
- Patient already enrolled in another therapeutic trial of an investigational drug
- HIV infection or active hepatitis B or C.
- Patient has a known allergy or hypersensitivity to any component of vorinostat or azacitidine.
Show all 13Show fewer
- Active cancer, or cancer during the year prior to trial entry other than basal cell carcinoma or carcinoma in situ of the cervix or breast.
- Less than 30 days since prior treatment with growth factors (EPO, G-CSF) or non-cytotoxic agents (including low-dose oral chemotherapy); in the event of prior treatment with cytotoxic or demethylating agents, an interval of 3 months is required;
- Patient is on any systemic steroids that have not been stabilized to the equivalent of ≤ 10 mg/day prednisone during the 4 weeks prior to the start of the study drugs.
- Patients with clinical evidence of CNS leukemia.
- Patient has a history of GI surgery or other procedures that might interfere with the absorption or swallowing of the study drugs.
- Women who are or could become pregnant, or who are currently breastfeeding
- Patient eligible for allotransplantation at the time of inclusion.
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
France24 sites
CHU d'Angers
Angers, 49033
CH Annecy
Annecy, 74374
Hôpital Avignon
Avignon, 84000
Centre hospitalier de la côte Basque
Bayonne, 64100
Hôpital Avicenne
Bobigny, 93009
CHU de Grenoble
Grenoble, 38043
CH Le mans
Le Mans, 72037
CH Lyon Sud
Lyon, 69495
IPC-Unité d'Hématologie 3
Marseille, 13273
CHU Nantes
Nantes, 44093
Hôpital Archet1
Nice, 06202
GHU Caremeau
Nîmes, 30029
Hôpital Saint Louis
Paris, 75010
Hopital Saint Louis - AP-HP, Hematology Dpt
Paris, 75475
Hôpital Saint-Louis
Paris, 75475
Hopital Cochin-Hematology
Paris, 75679
Centre Hospitalier Joffre
Perpignan, 66046
CHU de Haut-Lévèque
Pessac, 33604
Centre Henri Becquerel
Rouen, 76038
Hopital Purpan-Medecine interne
Toulouse, 31059
Hôpital PURPAN, Service d'Hématologie Clinique
Toulouse, 31059
CHU Bretonneau
Tours, 37044
CH de Valence
Valence, 26953
CHU Brabois
Vandœuvre-lès-Nancy, 54511
About this study
Official title: Addition of Suberoylanilide Hydroxamic Acid (Vorinostat) to Azacitidine in Patients With Higher Risk Myelodysplastic Syndromes (MDS): a Phase II add-on Study in Patients With Azacitidine Failure.
Azacytidine (AZA) is the current standard of care for frontline patient treated with high-risk MDS and is clinically active in all type of MDS, however, 50% of the patients will never respond. Vorinostat is an orally available HDAC inhibitor with clinical activity in MDS and proven in vitro synergy with AZA. Patient treated upfront with a combination of this agents have shown more responses based on phase I/II data. In the present study, we will use the combination of these two drugs to try to create a synergetic effect and generate a response for patients who experienced treatment failure after AZA.
All eligible patients will be treated with Azacitidine and oral vorinostat for 6 cycles of 28 days. Study Design
Read the detailed description
Patients who meet eligibility criteria will be administered vorinostat orally at 300mg two times daily for 7 days as outlined in table 1.1. AZA will be administered SC at 75 mg/m2/day x 7 consecutive days or at maximum tolerated dose if a dose reduction of AZA was needed before entering the trial with a minimum dose of 50mg/m2/d for 7 consecutive days.
Each cycle will last 28 days with AZA starting on day 1 of each cycle and vorinostat starting on day 3.
Patients will receive 6 cycles unless progression is documented. Patients with a complete remission (CR), partial remission (PR), or hematological improvement (HI), will be treated until progression.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Azacitidine and oral vorinostat
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azacitidine and oral vorinostatDrug
Also called Suberoylanilide Hydroxamic acid (Vorinostat), Azacitidine (Vidaza)
In patients still responding after six cycles, the drugs will continue to be supplied, and follow up until death or unacceptable tolerance will be continued in all patients.
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine and oral vorinostat | Experimental | Patients who meet eligibility criteria will be administered vorinostat orally at 300mg two times daily for 7 days. AZA will be administered SC at 75 mg/m2/day x 7 consecutive days or at maximum tolerated dose if a dose reduction of AZA was needed before entering the trial with a minimum dose of 50mg/m2/d for 7 consecutive days.
Each cycle will last 28 days with AZA starting on day 1 of each cycle and vorinostat starting on day 3. Receives: Drug: Azacitidine and oral vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
All eligible patients will be treated with Azacitidine and oral vorinostat for 6 cycles of 28 days.
The response rate (CR, PR, HI or marrow CR) will be evaluated after six cycles, according to IWG 2006.
In patients still responding after six cycles, the drugs will continue to be supplied, and follow up until death or unacceptable tolerance will be continued in all patients.
Complete Response (CR): Bone marrow: less than 5% myeloblasts with Peripheral blood: HI responses).
Partial remission (RP): Bone marrow blasts decreased by at least 50% but still more than 5% with Peripheral blood: HI responses).
Marrow CR:Bone marrow: maximum of 5% myeloblasts and decrease by at least 50% over pretreatment
HI (hematologic improvement)
- Erythroid response: Hgb increase at least by 1.5 g/dL
- Platelet response: Increase from less than 20x109/L to more than 20x109/L and by at least 100%
- Neutrophil response: At least 100% increase and an absolute increase of at least 0.5x109/L
Measured: 6 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2012 (estimated)
- Study startMar 2013
- Primary completionOct 2013
- Study completionJul 2015
Why it stopped: inefficiency
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 SyndromeStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Groupe Francophone des Myelodysplasies
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Thomas Prebet, MD, Principal investigator, Unité d'Hématologie-Institut Paoli Calmettes,MarseillePierre Fenaux, MD, Study director, Hôpital Saint Louis, hematology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01748240
- Sponsor's protocol ID
- GFM-Aza-Vor 2012-001401-25
- Acronym
- GFM-AZA-VOR
- Status last verified
- May 2019
- First submitted
- 7 Dec 2012
- Last updated
- 4 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Addition of Suberoylanilide Hydroxamic Acid (Vorinostat) to Azacitidine in Patients With Higher Risk Myelodysplastic Syndromes (MDS): a Phase II add-on Study in Patients With Azacitidine Failure.
- ClinicalTrials.gov ID
- NCT01748240
- Acronym / sponsor ID
- GFM-AZA-VOR / GFM-Aza-Vor 2012-001401-25
- Conditions
- Myelodysplastic Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: inefficiency
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Groupe Francophone des MyelodysplasiesUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Mar 2013
- Primary completion
- Oct 2013 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 12 Dec 2012 (estimated)
- Results
- Posted 10 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Azacytidine (AZA) is the current standard of care for frontline patient treated with high-risk MDS and is clinically active in all type of MDS, however, 50% of the patients will never respond. Vorinostat is an orally available HDAC inhibitor with clinical activity in MDS and proven in vitro synergy with AZA. Patient treated upfront with a combination of this agents have shown more responses based on phase I/II data. In the present study, we will use the combination of these two drugs to try to create a synergetic effect and generate a response for patients who experienced treatment failure after AZA.
All eligible patients will be treated with Azacitidine and oral vorinostat for 6 cycles of 28 days. Study Design
Detailed description
Patients who meet eligibility criteria will be administered vorinostat orally at 300mg two times daily for 7 days as outlined in table 1.1. AZA will be administered SC at 75 mg/m2/day x 7 consecutive days or at maximum tolerated dose if a dose reduction of AZA was needed before entering the trial with a minimum dose of 50mg/m2/d for 7 consecutive days.
Each cycle will last 28 days with AZA starting on day 1 of each cycle and vorinostat starting on day 3.
Patients will receive 6 cycles unless progression is documented. Patients with a complete remission (CR), partial remission (PR), or hematological improvement (HI), will be treated until progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azacitidine and oral vorinostat | Experimental | Drug: Azacitidine and oral vorinostatPatients who meet eligibility criteria will be administered vorinostat orally at 300mg two times daily for 7 days. AZA will be administered SC at 75 mg/m2/day x 7 consecutive days or at maximum tolerated dose if a dose reduction of AZA was needed before entering the trial with a minimum dose of 50mg/m2/d for 7 consecutive days. Each cycle will last 28 days with AZA starting on day 1 of each cycle and vorinostat starting on day 3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Myelodysplastic syndrome (WHO and FAB classified) including: RA, RARS, RCMD, RCMD-RS RAEB , RAEB-t and CMML with WBC < 13000/mm3)
- IPSS score 1.5 or higher (IPSS intermediate-2 and high risk categories) at the beginning of azacitidine,
- Absence of response (CR, PR, marrow CR or HI according to IWG 2006) after a minimum of 6 cycles of azacitidine single agent at 75 mg/m²/d for 7 days per cycle. Patients with a previous dose reduction of AZA may be eligible if the maximum tolerated dose was equal to or above 350mg/m2/cycle (i.e. 50 mg/m²/d for 7 days or 75mg/m2/d for 5 days).
- Age more or egal to 18 years
- ECOG performance status ≤ 2 (cf. appendix 2);
Key exclusion criteria (13 listed)
- Patient had prior treatment with an HDAC inhibitor (e.g., depsipeptide or NSC-630176, MS 275, LAQ-824, PXD-101, LBH589, MGCD0103, CRA024781, etc). Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study. Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period.
- Severe infection or any other uncontrolled severe condition.
- Last dose of AZA was given more than 3 months before entering the trial.
- Patient already enrolled in another therapeutic trial of an investigational drug
- HIV infection or active hepatitis B or C.
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 |
|---|---|---|
| Azacitidine and oral vorinostatAlso: Suberoylanilide Hydroxamic acid (Vorinostat), Azacitidine (Vidaza)In patients still responding after six cycles, the drugs will continue to be supplied, and follow up until death or unacceptable tolerance will be continued in all patients. | Drug | Azacitidine and oral vorinostat |
Primary outcome
Response Rate
Time frame: 6 month
All eligible patients will be treated with Azacitidine and oral vorinostat for 6 cycles of 28 days. The response rate (CR, PR, HI or marrow CR) will be evaluated after six cycles, according to IWG 2006. In patients still responding after six cycles, the drugs will continue to be supplied, and follow up until death or unacceptable tolerance will be continued in all patients. Complete Response (CR): Bone marrow: less than 5% myeloblasts with Peripheral blood: HI responses). Partial remission (RP): Bone marrow blasts decreased by at least 50% but still more than 5% with Peripheral blood: HI responses). Marrow CR:Bone marrow: maximum of 5% myeloblasts and decrease by at least 50% over pretreatment HI (hematologic improvement) * Erythroid response: Hgb increase at least by 1.5 g/dL * Platelet response: Increase from less than 20x109/L to more than 20x109/L and by at least 100% * Neutrophil response: At least 100% increase and an absolute increase of at least 0.5x109/L
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Myelodysplastic Syndrome
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
High Grade Myelodysplastic Syndromes
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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.
Thomas Prebet, MD principal investigator
Unité d'Hématologie-Institut Paoli Calmettes,Marseille
Pierre Fenaux, MD study director
Hôpital Saint Louis, hematology
24 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 Azacitidine and oral vorinostat in people with Myelodysplastic Syndrome, run by Groupe Francophone des Myelodysplasies at 24 sites in France.
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 16 inclusion and 13 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 4 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in France. 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 10 Aug 2018). 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?
Response Rate (time frame: 6 month). 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 4 Jun 2019.