Acute Myeloid LeukemiaPhase 2NCT02073838
Ribavirin and Hedgehog Inhibitor With or Without Decitabine in AML
A Phase 2 study testing Ribavirin, Vismodegib and Decitabine in people with Acute Myeloid Leukemia, run by Sarit Assouline at 1 site in Canada.
Trial summary
This is a research study of ribavirin which will be given in combination with vismodegib and/or decitabine. The purpose of this study is to see if patients respond to treatment when ribavirin is given with vismodegib alone or in combination with decitabine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Ribavirin, Vismodegib and Decitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteCanada
- Study dates
- May 2015to Nov 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 with AML M4 or M5 FAB subtype or high eIF4E are eligible.
- All patients must have failed primary therapy (defined as two induction chemotherapies), must have relapsed, or must not be suitable candidates for intensive induction chemotherapy.
- Patients who have a dry aspirate or extramedullary disease only are eligible for this study if they have a pre-treatment marrow or tissue biopsy demonstrating AML M4 or M5 subtype or high eIF4E.
- ECOG performance status 0, 1, 2.
- Life expectancy>4 weeks.
- Age is > 18 years.
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- Female patients of childbearing potential (FCBP) is defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy, or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). In addition, women under the age of 55 years must have a serum follicle stimulating hormone (FSH) level > 40IU/L to confirm menopause.
- FCBP must have a negative serum (beta-HCG) pregnancy test (minimum sensitivity 25 IU/L of equivalent units of HCG) within 7 days of starting treatment and must not be breastfeeding. Men and females of childbearing potential must agree to use two effective means of contraception, with one method being highly effective and the other method being either highly effective or less effective as listed below throughout the study and for at least 24 months after completion of protocol.
- An effective means of contraception includes the following:
- Male condoms with spermicide ii. Hormonal methods of contraception including combined oral contraception pills, vaginal ring, injectables, implants, and intrauterine devices (IUDs).
- Nonhormonal IUDs iv. Tubal ligation v. Vasectomy vi. Complete Abstinence
- A less effective means of contraception includes the following:
- Diaphragm with spermicide ii. Vaginal sponge iii. Male condom without spermicide iv. Progestin only pills by females of childbearing potential or male subject's FCBP partners v. Female condom (a male and female condom must not be used together)
- Male subjects must not donate semen while on study and during 24 months after treatment discontinuation.
- Adequate renal and hepatic function: serum creatinine < 1.5 x ULN; AST or ALT < 2.5 x ULN (or < 5 x ULN if liver involvement with leukemia); serum bilirubin < 1.5 x ULN
- Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained.
- Accessible for treatment and follow up.
Who cannot join
- Patients with impaired ribavirin uptake. As tested in the central laboratory.
- Uncontrolled central nervous system involvement by AML.
- Active cardiovascular disease as defined by New York Heart Association (NYHA) class III-IV categorization.
- Patients with hemoglobinopathies which may affect their ability to tolerate ribavirin.
- Intercurrent illness or medical condition precluding safe administration of the planned protocol treatment or required follow-up.
- Received any previous therapy for AML within 28 days prior to the study entry. Hydrea is permitted for the treatment of leukocytosis but must be stopped prior to starting study drugs.
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- Female patients who are pregnant or breastfeeding.
- Concurrent treatment with other anti-cancer therapy except adjuvant antihormonal agents for breast cancer or for limited stage prostate cancer.
- Known infection with HIV.
- History of other active malignancy. Subjects who have been disease-free for 2 year or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
- FAB AML M1, 2, 6, 7 will be excluded if they do not have high eIF4E expression. AML M3 is always excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II, Multi-center, Open Label, Randomized Study of Ribavirin and Hedgehog Inhibitor With or Without Decitabine in Acute Myeloid Leukemia (AML)
This is a research study of ribavirin which will be given in combination with vismodegib and/or decitabine. The purpose of this study is to see if patients respond to treatment when ribavirin is given with vismodegib alone or in combination with decitabine.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Ribavirin, Vismodegib, Decitabine
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RibavirinDrug
VismodegibDrug
DecitabineDrug
| Study group | Role | What they receive |
|---|---|---|
| Ribavirin, vismodegib, decitabine | Experimental | Decitabine 20mg/m2 IV QD days -7 to -3 for cycle 1. Ribavirin 1400mg BID and vismodegib 150mg QD starting on day 1. On subsequent cycles, decitabine will be administered on days 1 to 5. Receives: Drug: Ribavirin; Drug: Vismodegib; Drug: Decitabine |
| Ribavirin, vismodegib | Experimental | Ribavirin 1400mg BID, vismodegib 150mg QD Receives: Drug: Ribavirin; Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy will be measured by overall response rate (ORR).
Measured: Measured up to 2 years after the last subject has enrolled in the study.
Secondary outcomes (7)
Time to response
Measured: Measured up to 2 years after the last subject has enrolled in the study.
Duration of response
Measured: Measured up to 2 years after the last subject has enrolled in the study.
One year survival
Measured: Measured up to 2 years after the last subject has enrolled in the study.
Overall survival
Measured: Measured up to 3 years after the last subject has enrolled in the study.
Hematologic improvement defined by the number of individual, positively affected cell lines (erythroid, neutrophil and platelet cells) per patient.
Measured: Measured up to 2 years after the last subject has enrolled in the study.
Number of participants with Adverse Events as a Measure of Safety and Tolerability
Measured: Measured up to 2 years after the last subject has enrolled in the study.
Changes in eIF4E expression, localization, and signalling pathways (measured by immuno-histochemical analysis, PCR or western blot) and correlating with each patient's overall response.
Measured: Measured up to 2 years after the last subject has enrolled in the study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2014 (estimated)
- Study startMay 2015
- Primary completionNov 2022
- Study completionNov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sarit Assouline
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Sarit Assouline, Jewish General Hospital
- Investigators
- Sarit Assouline, MD, Principal investigator, Jewish General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02073838
- Sponsor's protocol ID
- Ribavirin=005
- Status last verified
- Sep 2023
- First submitted
- 21 Feb 2014
- Last updated
- 29 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Mazewski C, Platanias LC. A novel approach to overcome drug resistance in acute myeloid leukemia. Haematologica. 2023 Nov 1;108(11):2889-2890. doi: 10.3324/haematol.2023.283099. No abstract available.
PubMed 37165841Assouline S, Gasiorek J, Bergeron J, Lambert C, Culjkovic-Kraljacic B, Cocolakis E, Zakaria C, Szlachtycz D, Yee K, Borden KLB. Molecular targeting of the UDP-glucuronosyltransferase enzymes in high-eukaryotic translation initiation factor 4E refractory/relapsed acute myeloid leukemia patients: a randomized phase II trial of vismodegib, ribavirin with or without decitabine. Haematologica. 2023 Nov 1;108(11):2946-2958. doi: 10.3324/haematol.2023.282791.
PubMed 36951168
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Multi-center, Open Label, Randomized Study of Ribavirin and Hedgehog Inhibitor With or Without Decitabine in Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT02073838
- Acronym / sponsor ID
- Ribavirin=005
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Sarit AssoulineUniversity, hospital or other
- Study start
- May 2015 (actual)
- Primary completion
- Nov 2022 (actual)
- Study completion
- Nov 2022 (actual)
- First posted
- 27 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a research study of ribavirin which will be given in combination with vismodegib and/or decitabine. The purpose of this study is to see if patients respond to treatment when ribavirin is given with vismodegib alone or in combination with decitabine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ribavirin, vismodegib, decitabine | Experimental | Drug: Ribavirin, Drug: Vismodegib, Drug: DecitabineDecitabine 20mg/m2 IV QD days -7 to -3 for cycle 1. Ribavirin 1400mg BID and vismodegib 150mg QD starting on day 1. On subsequent cycles, decitabine will be administered on days 1 to 5. |
| Ribavirin, vismodegib | Experimental | Drug: Ribavirin, Drug: DecitabineRibavirin 1400mg BID, vismodegib 150mg QD |
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 with AML M4 or M5 FAB subtype or high eIF4E are eligible.
- All patients must have failed primary therapy (defined as two induction chemotherapies), must have relapsed, or must not be suitable candidates for intensive induction chemotherapy.
- Patients who have a dry aspirate or extramedullary disease only are eligible for this study if they have a pre-treatment marrow or tissue biopsy demonstrating AML M4 or M5 subtype or high eIF4E.
- ECOG performance status 0, 1, 2.
- Life expectancy>4 weeks.
Key exclusion criteria (11 listed)
- Patients with impaired ribavirin uptake. As tested in the central laboratory.
- Uncontrolled central nervous system involvement by AML.
- Active cardiovascular disease as defined by New York Heart Association (NYHA) class III-IV categorization.
- Patients with hemoglobinopathies which may affect their ability to tolerate ribavirin.
- Intercurrent illness or medical condition precluding safe administration of the planned protocol treatment or required follow-up.
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 |
|---|---|---|
| Ribavirin | Drug | Ribavirin, vismodegib, Ribavirin, vismodegib, decitabine |
| Vismodegib | Drug | Ribavirin, vismodegib, decitabine |
| Decitabine | Drug | Ribavirin, vismodegib, Ribavirin, vismodegib, decitabine |
Primary outcome
Efficacy will be measured by overall response rate (ORR).
Time frame: Measured up to 2 years after the last subject has enrolled in the study.
7 secondary outcomes
Time to response
Time frame: Measured up to 2 years after the last subject has enrolled in the study.
Duration of response
Time frame: Measured up to 2 years after the last subject has enrolled in the study.
One year survival
Time frame: Measured up to 2 years after the last subject has enrolled in the study.
Overall survival
Time frame: Measured up to 3 years after the last subject has enrolled in the study.
Hematologic improvement defined by the number of individual, positively affected cell lines (erythroid, neutrophil and platelet cells) per patient.
Time frame: Measured up to 2 years after the last subject has enrolled in the study.
Number of participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: Measured up to 2 years after the last subject has enrolled in the study.
Changes in eIF4E expression, localization, and signalling pathways (measured by immuno-histochemical analysis, PCR or western blot) and correlating with each patient's overall response.
Time frame: Measured up to 2 years after the last subject has enrolled in the study.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2023.
- Derived from this study: PubMed 37165841Mazewski C, Platanias LC. A novel approach to overcome drug resistance in acute myeloid leukemia. Haematologica. 2023 Nov 1;108(11):2889-2890. doi: 10.3324/haematol.2023.283099. No abstract available.
- Derived from this study: PubMed 36951168Assouline S, Gasiorek J, Bergeron J, Lambert C, Culjkovic-Kraljacic B, Cocolakis E, Zakaria C, Szlachtycz D, Yee K, Borden KLB. Molecular targeting of the UDP-glucuronosyltransferase enzymes in high-eukaryotic translation initiation factor 4E refractory/relapsed acute myeloid leukemia patients: a randomized phase II trial of vismodegib, ribavirin with or without decitabine. Haematologica. 2023 Nov 1;108(11):2946-2958. doi: 10.3324/haematol.2023.282791.
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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.
Sarit Assouline, MD principal investigator
Jewish General Hospital
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 Ribavirin, Vismodegib and Decitabine in people with Acute Myeloid Leukemia, run by Sarit Assouline at 1 site in Canada.
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 11 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 29 Sep 2023. 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 Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Efficacy will be measured by overall response rate (ORR). (time frame: Measured up to 2 years after the last subject has enrolled in the study.). 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 NCT02073838, which also lists 2 linked publications.
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 29 Sep 2023.