Hodgkin's LymphomaPhase 1/2NCT00496431
phII Study of an HDAC Inhibitor in Very High-risk Relapsed/Refractory Hodgkin's Lymphoma Patients
A Phase 1/2 study testing histone deacetylase inhibitor (ITF2357) in people with Hodgkin's Lymphoma, run by Italfarmaco at 1 site in Italy.
Trial summary
PRIMARY OBJECTIVE To evaluate the efficacy (according to the International Working Group response criteria for Hodgkin's Lymphomas [7, 8, 9]) of daily oral doses of ITF2357 administered to very high-risk Hodgkin's lymphoma patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hodgkin's Lymphoma
- What is being tested?
- histone deacetylase inhibitor (ITF2357)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteItaly
- Study dates
- May 2007to Mar 2009
- Phase
- Phase 1/2
- 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
- Signed Informed Consent Form; Age ≥ 18 years; History of histologically confirmed Hodgkin's lymphoma Subjects are eligible for this trial if (1) they have failed at least 1 cycle of chemotherapy, with or without radiotherapy, and if (2) they are considered incurable by the referring physician, and would be treated with second-line or subsequent-line salvage regimens, mainly with palliative intent; Clinical laboratory values ANC > 1500/µL; Platelet count > 75000/µL Hemoglobin > 9 g/dL (may not be transfused or treated with erythropoietin to maintain or exceed this level) Total bilirubin < 1.6 mg/dL; AST or ALT < 2.5 times the upper limit of normal Serum creatinine < 2.0 mg/dL or creatinine clearance > 50 mL/min Serum Potassium and Magnesium within normal limits; Measurable disease (according to the International Working Group response criteria for HL); ECOG performance status of 0 or 1; Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential (use per institutional standard); Life expectancy of > 3 months;; At least 4 weeks since last treatment for HL Willingness and capability to comply with the requirements of the study;
Who cannot join
- Active bacterial or mycotic infection requiring antimicrobial treatment on Day 1; Pregnancy or lactation; A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 ms, according to Bazett's correction formula); The use of concomitant medications that prolong the QT/QTc interval;
- Clinically significant cardiovascular disease e.g.:
- Uncontrolled hypertension, myocardial infarction, unstable angina New York Heart Association (NYHA) Grade II or greater congestive heart failure History of any cardiac arrhythmia requiring medication (irrespective of its severity) Grade II or greater peripheral vascular disease A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome); Positive blood test for HIV, HBV and HCV; Identification of viral DNA by quantitative PCR for EBV (Ebstein Barr virus), JC virus, CMV (Cytomegalovirus) and Herpes Zoster; History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications;
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study of the Histone-deacetylase Inhibitor ITF2357 in Very High-risk Relapsed/Refractory Hodgkin's Lymphoma Patients
PRIMARY OBJECTIVE
- To evaluate the efficacy (according to the International Working Group response criteria for Hodgkin's Lymphomas [7, 8, 9]) of daily oral doses of ITF2357 administered to very high-risk Hodgkin's lymphoma patients.
SECONDARY OBJECTIVES
- To evaluate safety and tolerability of multiple oral doses of ITF2357
- To assess the proportion of patients that, after ITF2357 treatment, can undergo high-dose salvage chemotherapy with either autografting or allografting
Read the detailed description
This is a multi-center, open label, phase II study testing ITF2357 in a population of very high-risk relapsed/refractory Hodgkin's lymphoma patients.
The patients were planned to receive 50 mg ITF2357 four times a day at 6-hour intervals in fed conditions for 28 consecutive days unless evidence of progressive disease, presence of unacceptable adverse events or patient's request to discontinue treatment occurs.
Decision regarding the continuation of ITF2357 were made on:
- the basis of tumor reassessment upon completion of cycle defined as above and not later than 7 days and
- the occurred toxicity (if any).
If complete response or partial response or stabilization of disease after first cycle, without concomitant relevant toxicities is observed, the treatment may continue as long as there is no evidence of progressive disease or appearance of unacceptable adverse events.
In any case, the treatment is not planned to exceed 84 days of drug intake overall (i.e. 12 weeks).
The treatment is planned to be administered on an outpatient basis and patients are planned to be followed regularly with physical and laboratory tests, as specified in the protocol; in case of hospitalization, the treatment will be continued or interrupted according to the Investigators' decision.
The study planned to accrue 23 patients evaluable for efficacy and the anticipated duration of the study is about 18 months.
Actually, accrual was stopped earlier than planned by the Sponsor for 2 main reasons: a) a very slow recruitment rate; b) an unplanned interim analysis suggesting a lower than estimated efficacy of the drug when delivered as single agent.
- Conditions
- Hodgkin's Lymphoma
- Being tested
- histone deacetylase inhibitor (ITF2357)
- Medical subject headings
- Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
histone deacetylase inhibitor (ITF2357)Drug
Also called Givinostat
50 mg b.i.d. (or every 8 hours or every 6 hours), every day
| Study group | Role | What they receive |
|---|---|---|
| ITF2357 | Experimental | Patients were provided with the appropriate number of 50 mg hard gelatine capsules for oral administration for 7 days treatment, i.e. at the daily dose of 100 mg, 14 capsules 50 mg each, plus 2 spare capsules suitable in case of accidental loss. Receives: Drug: histone deacetylase inhibitor (ITF2357) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total number of Objective Responses (OR): Complete Responses (CR) and Partial Responses (PR)
The objective response of the patients was assessed as complete response or partial response after ITF2357 treatment.
Measured: every 28 days
Secondary outcomes (1)
Number of subjects experiencing an Adverse Events
Type, frequency, severity, timing and relatedness of AEs (including changes in vital signs and clinical laboratory results) proportion of patients that, after ITF2357 treatment, can undergo high-dose salvage chemotherapy with either autografting or allografting.
Measured: Throughout the study till follow-up after 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2007 (estimated)
- Study startMay 2007
- Primary completionMar 2009
- Study completionMar 2009
Why it stopped: Study accrual was stopped earlier than planned by the Sponsor for 2 main reasons: very slow recruitment rate; lower than estimated efficacy of the drug when delivered as single agent.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hodgkin's LymphomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Italfarmaco
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alessandro Massimo Gianni, MD, Principal investigator, Istituto Nazionale per lo studio e la cura dei Tumori (Milan - Italy)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00496431
- Sponsor's protocol ID
- DSC/07/2357/26
- Other IDs
- 2007-000049-36
- Status last verified
- Jan 2022
- First submitted
- 3 Jul 2007
- Last updated
- 27 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of the Histone-deacetylase Inhibitor ITF2357 in Very High-risk Relapsed/Refractory Hodgkin's Lymphoma Patients
- ClinicalTrials.gov ID
- NCT00496431
- Acronym / sponsor ID
- DSC/07/2357/26
- Conditions
- Hodgkin's Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study accrual was stopped earlier than planned by the Sponsor for 2 main reasons: very slow recruitment rate; lower than estimated efficacy of the drug when delivered as single agent.
- Enrolment
- 19 participants (actual)
- Lead sponsor
- ItalfarmacoIndustry (pharma, biotech, devices)
- Study start
- May 2007
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 4 Jul 2007 (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.
PRIMARY OBJECTIVE
- To evaluate the efficacy (according to the International Working Group response criteria for Hodgkin's Lymphomas [7, 8, 9]) of daily oral doses of ITF2357 administered to very high-risk Hodgkin's lymphoma patients.
SECONDARY OBJECTIVES
- To evaluate safety and tolerability of multiple oral doses of ITF2357
- To assess the proportion of patients that, after ITF2357 treatment, can undergo high-dose salvage chemotherapy with either autografting or allografting
Detailed description
This is a multi-center, open label, phase II study testing ITF2357 in a population of very high-risk relapsed/refractory Hodgkin's lymphoma patients.
The patients were planned to receive 50 mg ITF2357 four times a day at 6-hour intervals in fed conditions for 28 consecutive days unless evidence of progressive disease, presence of unacceptable adverse events or patient's request to discontinue treatment occurs.
Decision regarding the continuation of ITF2357 were made on:
- the basis of tumor reassessment upon completion of cycle defined as above and not later than 7 days and
- the occurred toxicity (if any).
If complete response or partial response or stabilization of disease after first cycle, without concomitant relevant toxicities is observed, the treatment may continue as long as there is no evidence of progressive disease or appearance of unacceptable adverse events.
In any case, the treatment is not planned to exceed 84 days of drug intake overall (i.e. 12 weeks).
The treatment is planned to be administered on an outpatient basis and patients are planned to be followed regularly with physical and laboratory tests, as specified in the protocol; in case of hospitalization, the treatment will be continued or interrupted according to the Investigators' decision.
The study planned to accrue 23 patients evaluable for efficacy and the anticipated duration of the study is about 18 months.
Actually, accrual was stopped earlier than planned by the Sponsor for 2 main reasons: a) a very slow recruitment rate; b) an unplanned interim analysis suggesting a lower than estimated efficacy of the drug when delivered as single agent.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ITF2357 | Experimental | Drug: histone deacetylase inhibitor (ITF2357)Patients were provided with the appropriate number of 50 mg hard gelatine capsules for oral administration for 7 days treatment, i.e. at the daily dose of 100 mg, 14 capsules 50 mg each, plus 2 spare capsules suitable in case of accidental loss. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Signed Informed Consent Form; Age ≥ 18 years; History of histologically confirmed Hodgkin's lymphoma Subjects are eligible for this trial if (1) they have failed at least 1 cycle of chemotherapy, with or without radiotherapy, and if (2) they are considered incurable by the referring physician, and would be treated with second-line or subsequent-line salvage regimens, mainly with palliative intent; Clinical laboratory values ANC > 1500/µL; Platelet count > 75000/µL Hemoglobin > 9 g/dL (may not be transfused or treated with erythropoietin to maintain or exceed this level) Total bilirubin < 1.6 mg/dL; AST or ALT < 2.5 times the upper limit of normal Serum creatinine < 2.0 mg/dL or creatinine clearance > 50 mL/min Serum Potassium and Magnesium within normal limits; Measurable disease (according to the International Working Group response criteria for HL); ECOG performance status of 0 or 1; Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential (use per institutional standard); Life expectancy of > 3 months;; At least 4 weeks since last treatment for HL Willingness and capability to comply with the requirements of the study;
Key exclusion criteria (3 listed)
- Active bacterial or mycotic infection requiring antimicrobial treatment on Day 1; Pregnancy or lactation; A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 ms, according to Bazett's correction formula); The use of concomitant medications that prolong the QT/QTc interval;
- Uncontrolled hypertension, myocardial infarction, unstable angina New York Heart Association (NYHA) Grade II or greater congestive heart failure History of any cardiac arrhythmia requiring medication (irrespective of its severity) Grade II or greater peripheral vascular disease A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome); Positive blood test for HIV, HBV and HCV; Identification of viral DNA by quantitative PCR for EBV (Ebstein Barr virus), JC virus, CMV (Cytomegalovirus) and Herpes Zoster; History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications;
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 |
|---|---|---|
| histone deacetylase inhibitor (ITF2357)Also: Givinostat50 mg b.i.d. (or every 8 hours or every 6 hours), every day | Drug | ITF2357 |
Primary outcome
Total number of Objective Responses (OR): Complete Responses (CR) and Partial Responses (PR)
Time frame: every 28 days
The objective response of the patients was assessed as complete response or partial response after ITF2357 treatment.
1 secondary outcome
Number of subjects experiencing an Adverse Events
Time frame: Throughout the study till follow-up after 3 months
Results and safety
The study was stopped early (reason given: Study accrual was stopped earlier than planned by the Sponsor for 2 main reasons: very slow recruitment rate; lower than estimated efficacy of the drug when delivered as single agent.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2022.
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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.
Alessandro Massimo Gianni, MD principal investigator
Istituto Nazionale per lo studio e la cura dei Tumori (Milan - Italy)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing histone deacetylase inhibitor (ITF2357) in people with Hodgkin's Lymphoma, run by Italfarmaco at 1 site in Italy.
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 1 inclusion and 3 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 27 Jan 2022. 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 Italy. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was stopped early (reason given: Study accrual was stopped earlier than planned by the Sponsor for 2 main reasons: very slow recruitment rate; lower than estimated efficacy of the drug when delivered as single agent.). Results are not available in the source record.
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?
Total number of Objective Responses (OR): Complete Responses (CR) and Partial Responses (PR) (time frame: every 28 days). 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 27 Jan 2022.