Multiple MyelomaPhase 2NCT00792506
Phase II Clinical Trial of ITF2357 In Patients With Relapsed/Refractory Multiple Myeloma
A Phase 2 study testing ITF2357 in people with Multiple Myeloma, run by Italfarmaco at 1 site in Italy.
Trial summary
Primary objective: To assess the safety of ITF 2357 administered once weekly at high pulse dose in patients with relapsing/refractory multiple myeloma. Secondary objectives: 1. To evaluate the anti-tumour activity of ITF 2357 administered once weekly at high pulse dose in patients with advanced multiple myeloma… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- ITF2357
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteItaly
- Study dates
- Oct 2008to Jul 2010
- 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
- Established diagnosis of multiple myeloma according to International Myeloma Working Group diagnostic criteria
- Age ≥ 18 years
- Patient relapsed after at least 2 lines of conventional chemotherapy or high dose therapy with autologous or allogeneic stem cell support, and/or for whom no alternative treatments are available/suitable
- Increasing trend of monoclonal immunoglobulin or Bence-Jones proteinuria through the last 4 consecutive pre-screening measurements, already available in the patient history
- No chemotherapy or other investigational anticancer therapy for at least 3 weeks before the start of the study
- Full recovery from previous toxicities
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- ECOG performance status 0-2
- Adequate bone marrow reserve: absolute neutrophil count ≥ 1000/ml; platelet count ≥ 90000/ml
- Adequate liver function: total bilirubin within normal institutional limits (PI center); AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal (PI center)
- Adequate renal function: Creatinine ≤ 2.5 mg/dl or creatinine clearance ≥ 50 ml/min
- Either men or women, accepting to practice effective contraception during the entire study period unless documentation of infertility exists. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should immediately inform her treating physician; in this case ITF 2357 treatment will be promptly discontinued
- Able to understand and willing to sign the informed consent form.
Who cannot join
- Planned autologous or allogeneic bone marrow transplantation within 4 weeks of the initiation of ITF 2357 administration
- Concurrent use of medicines that would confound the interpretation of toxicities and anti-tumour activity of ITF 2357 (i.e. quinolones, macrolides, 5-HT3 antagonists except for palonosetron,)
- Clinically significant illness including, but not limited to, the following: active infection, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, cardiac arrhythmia (present or documented in the past, of any kind), any other condition (including laboratory abnormalities) that in the opinion of the Investigator places the patient to unacceptable risk for adverse outcome if he/she were to participate in the study
- Psychiatric illness/social situations that would limit compliance with study medication and protocol requirements
- Pregnant or lactating women
- Positive blood tests for HIV, HBV, HCV, active EBV and CMV
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- Diseases related to active viral infections
- Patients with a marked baseline prolongation of QTc interval (e.g. repeated demonstration of a QTc interval >440 ms for men and >450 ms for women)
- Patients with history of additional risk factors for Torsade de Pointes (e.g. heart failure, family history of Long QT Syndrome).
- The use of concomitant medications with potential risk of Torsade de Pointes and/or that can prolong QTc interval
- -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II High Pulse Dose Clinical Trial of Orally Administered ITF2357 In Patients With Relapsed/Refractory Multiple Myeloma
Primary objective:
To assess the safety of ITF 2357 administered once weekly at high pulse dose in patients with relapsing/refractory multiple myeloma.
Secondary objectives:
- To evaluate the anti-tumour activity of ITF 2357 administered once weekly at high pulse dose in patients with advanced multiple myeloma, measured as decrease of M protein.
- To assess the therapeutic response to ITF3257 according to EBMT criteria.
- To determine pharmacokinetic profile of ITF 2357 administered following high pulse dose schedule.
Read the detailed description
This is open label, phase IIa High Pulse Dose Clinical Trial testing ITF2357 (orally administered) in adult patients with relapsing/refractory multiple myeloma after at least 2 previous lines of treatment.
Patients are planned to receive ITF2357 in accordance with following scheme:
Weeks 1-6
Patient #01 is planned to receive ITF 2357 at 400 mg in one single dose on day 1, 8, 15, 22, 29 and 36. Safety assessments are planned to be performed twice a week. If no issue (grade >3 neutropenia or any other grade ≥3 toxicity) emerges at day 15, two further patients (#02 and #03) will be enrolled and receive the same dose. If patients #02 and #03 show a favourable safety profile at day 15, and in the meantime no safety concerns arise from patient #01, the further patients will be enrolled and treated according to the below reported scheme:
- 8 more patients (#04-11) will receive 400 mg once weekly; safety assessments will be performed weekly.
- 1 patient (#12) will receive 600 mg once weekly; safety assessments will be performed twice a week.
If no safety concern emerges from patient 12 at day 15, two further patients (#13 and #14) will be enrolled and treated with 600 mg once weekly. If patients #13 and #14 don't show relevant safety concerns (grade >3 neutropenia or any other grade ≥3 toxicity) at day 15, and in the meanwhile patient #12 maintains a favourable safety profile, eight further patients (#15-22) will be recruited and receive the same treatment regimen.
If grade >3 neutropenia or any other grade ≥3 toxicity appear at any time during week 1-6, the treatment will be permanently discontinued.
In this phase, treatment will be administered on an inpatient basis.
Weeks 7-12
For patients still on therapy at day 43 visit, M protein will be quantified and the treatment continued or possibly modified as follows on the basis of this parameter:
Decrease >or= of 25%:
patients in 400/week group continue 400mg for 6 further weeks patients in 600/week group continue 600mg for 6 further weeks
Stable +or- of 25%:
patients in 400/week group increase to 600mg and continue for 6 further weeks patients in 600/week group add dexamethasone 40mg for 4 days/week (day 1-4) and continue 600mg for 6 further weeks
Increase > of 25%:
patients in 400/week group add dexamethasone 40mg for 4 days/week (day 1-4) and continue 400mg for 6 further weeks patients in 600/week group failure:out of the study patients in 600/week group
Safety assessments will be performed at weekly intervals. In case of grade >3 neutropenia or any other grade ≥3 toxicity the treatment will be permanently discontinued.
In this phase treatment will be administered on an inpatient basis.
Weeks 13-18
For patients still on therapy at day 85 (week 13, day 1), the response rate will be quantified according to EBMT criteria. In case of response (complete, partial or minimal) or stable disease (no change) the treatment will be prolonged until week 18, whereas in case of disease progression the patient will leave the study. A new complete efficacy evaluation will be performed at day 127 (end of treatment).
During this phase safety will be assessed at weekly intervals and in case of grade >3 neutropenia or any other grade ≥3 toxicity the treatment will be permanently discontinued.
This phase of the study will be conducted on an outpatient basis.
No dosage modification or temporary discontinuation is admitted.
Only one patient has been enrolled. The drug was ineffective in determining an improvement of the patient's disease status according to the EBMT response criteria.The study was prematurely discontinued for lack of recruitment.No firm conclusion on the safety and efficacy of ITF2357 administered at high (400 or 600 mg) single weekly doses can be drawn from the data collected from the only one patient recruited.
- Conditions
- Multiple Myeloma
- Being tested
- ITF2357
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ITF2357Drug
Also called Histone-Deacetylase Inhibitor
Treatment was to be administered on an inpatient basis from week 1 to week 13 and on an outpatient basis from week 14 to anticipated end of treatment (week 18). The patients had to be hospitalized on day 1 every week. The Investigator had to administer ITF 2357 in one single dose (two or three 200 mg capsules at one time) under his/her direct control.
| Study group | Role | What they receive |
|---|---|---|
| ITF2357 | Experimental | Eligible patients had to be treated with weekly single doses of ITF2357 according to the above mentioned treatment plan. Receives: Drug: ITF2357 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with relapsing/refractory multiple myeloma with TEAE, included serious AE
Number of patients with TEAE, included serious AE, was assessed while receiving once weekly ITF2357 at high pulse dose.
Measured: 30 weeks
Secondary outcomes (1)
Decrease in M protein and clinical response rate (PR plus CR according to the European Group for Blood & Marrow Transplantation - EBMT- criteria).
Anti-tumour activity of ITF 2357 was measured as decrease of M protein. While the clinical response rate was represented by a Partial or complete response according to the EBMT criteria.
Measured: 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2008 (estimated)
- Study startOct 2008
- Primary completionJan 2010
- Study completionJul 2010
Why it stopped: The study was prematurely discontinued for lack of recruitement.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Italfarmaco
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Giorgio La Nasa, MD, Principal investigator, Presidio Ospedaliero R. Binaghi, Cagliari - Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00792506
- Sponsor's protocol ID
- DSC/07/2357/29
- Other IDs
- 2008-001416-20, 2008
- Status last verified
- Jan 2022
- First submitted
- 14 Nov 2008
- Last updated
- 2 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II High Pulse Dose Clinical Trial of Orally Administered ITF2357 In Patients With Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00792506
- Acronym / sponsor ID
- DSC/07/2357/29
- Conditions
- Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was prematurely discontinued for lack of recruitement.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- ItalfarmacoIndustry (pharma, biotech, devices)
- Study start
- Oct 2008
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 18 Nov 2008 (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 assess the safety of ITF 2357 administered once weekly at high pulse dose in patients with relapsing/refractory multiple myeloma.
Secondary objectives:
- To evaluate the anti-tumour activity of ITF 2357 administered once weekly at high pulse dose in patients with advanced multiple myeloma, measured as decrease of M protein.
- To assess the therapeutic response to ITF3257 according to EBMT criteria.
- To determine pharmacokinetic profile of ITF 2357 administered following high pulse dose schedule.
Detailed description
This is open label, phase IIa High Pulse Dose Clinical Trial testing ITF2357 (orally administered) in adult patients with relapsing/refractory multiple myeloma after at least 2 previous lines of treatment.
Patients are planned to receive ITF2357 in accordance with following scheme:
Weeks 1-6
Patient #01 is planned to receive ITF 2357 at 400 mg in one single dose on day 1, 8, 15, 22, 29 and 36. Safety assessments are planned to be performed twice a week. If no issue (grade >3 neutropenia or any other grade ≥3 toxicity) emerges at day 15, two further patients (#02 and #03) will be enrolled and receive the same dose. If patients #02 and #03 show a favourable safety profile at day 15, and in the meantime no safety concerns arise from patient #01, the further patients will be enrolled and treated according to the below reported scheme:
- 8 more patients (#04-11) will receive 400 mg once weekly; safety assessments will be performed weekly.
- 1 patient (#12) will receive 600 mg once weekly; safety assessments will be performed twice a week.
If no safety concern emerges from patient 12 at day 15, two further patients (#13 and #14) will be enrolled and treated with 600 mg once weekly. If patients #13 and #14 don't show relevant safety concerns (grade >3 neutropenia or any other grade ≥3 toxicity) at day 15, and in the meanwhile patient #12 maintains a favourable safety profile, eight further patients (#15-22) will be recruited and receive the same treatment regimen.
If grade >3 neutropenia or any other grade ≥3 toxicity appear at any time during week 1-6, the treatment will be permanently discontinued.
In this phase, treatment will be administered on an inpatient basis.
Weeks 7-12
For patients still on therapy at day 43 visit, M protein will be quantified and the treatment continued or possibly modified as follows on the basis of this parameter:
Decrease >or= of 25%:
patients in 400/week group continue 400mg for 6 further weeks patients in 600/week group continue 600mg for 6 further weeks
Stable +or- of 25%:
patients in 400/week group increase to 600mg and continue for 6 further weeks patients in 600/week group add dexamethasone 40mg for 4 days/week (day 1-4) and continue 600mg for 6 further weeks
Increase > of 25%:
patients in 400/week group add dexamethasone 40mg for 4 days/week (day 1-4) and continue 400mg for 6 further weeks patients in 600/week group failure:out of the study patients in 600/week group
Safety assessments will be performed at weekly intervals. In case of grade >3 neutropenia or any other grade ≥3 toxicity the treatment will be permanently discontinued.
In this phase treatment will be administered on an inpatient basis.
Weeks 13-18
For patients still on therapy at day 85 (week 13, day 1), the response rate will be quantified according to EBMT criteria. In case of response (complete, partial or minimal) or stable disease (no change) the treatment will be prolonged until week 18, whereas in case of disease progression the patient will leave the study. A new complete efficacy evaluation will be performed at day 127 (end of treatment).
During this phase safety will be assessed at weekly intervals and in case of grade >3 neutropenia or any other grade ≥3 toxicity the treatment will be permanently discontinued.
This phase of the study will be conducted on an outpatient basis.
No dosage modification or temporary discontinuation is admitted.
Only one patient has been enrolled. The drug was ineffective in determining an improvement of the patient's disease status according to the EBMT response criteria.The study was prematurely discontinued for lack of recruitment.No firm conclusion on the safety and efficacy of ITF2357 administered at high (400 or 600 mg) single weekly doses can be drawn from the data collected from the only one patient recruited.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ITF2357 | Experimental | Drug: ITF2357Eligible patients had to be treated with weekly single doses of ITF2357 according to the above mentioned treatment plan. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Established diagnosis of multiple myeloma according to International Myeloma Working Group diagnostic criteria
- Age ≥ 18 years
- Patient relapsed after at least 2 lines of conventional chemotherapy or high dose therapy with autologous or allogeneic stem cell support, and/or for whom no alternative treatments are available/suitable
- Increasing trend of monoclonal immunoglobulin or Bence-Jones proteinuria through the last 4 consecutive pre-screening measurements, already available in the patient history
- No chemotherapy or other investigational anticancer therapy for at least 3 weeks before the start of the study
Key exclusion criteria (11 listed)
- Planned autologous or allogeneic bone marrow transplantation within 4 weeks of the initiation of ITF 2357 administration
- Concurrent use of medicines that would confound the interpretation of toxicities and anti-tumour activity of ITF 2357 (i.e. quinolones, macrolides, 5-HT3 antagonists except for palonosetron,)
- Clinically significant illness including, but not limited to, the following: active infection, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, cardiac arrhythmia (present or documented in the past, of any kind), any other condition (including laboratory abnormalities) that in the opinion of the Investigator places the patient to unacceptable risk for adverse outcome if he/she were to participate in the study
- Psychiatric illness/social situations that would limit compliance with study medication and protocol requirements
- Pregnant or lactating women
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 |
|---|---|---|
| ITF2357Also: Histone-Deacetylase InhibitorTreatment was to be administered on an inpatient basis from week 1 to week 13 and on an outpatient basis from week 14 to anticipated end of treatment (week 18). The patients had to be hospitalized on day 1 every week. The Investigator had to administer ITF 2357 in one single dose (two or three 200 mg capsules at one time) under his/her direct control. | Drug | ITF2357 |
Primary outcome
Number of patients with relapsing/refractory multiple myeloma with TEAE, included serious AE
Time frame: 30 weeks
Number of patients with TEAE, included serious AE, was assessed while receiving once weekly ITF2357 at high pulse dose.
1 secondary outcome
Decrease in M protein and clinical response rate (PR plus CR according to the European Group for Blood & Marrow Transplantation - EBMT- criteria).
Time frame: 18 weeks
Results and safety
The study was stopped early (reason given: The study was prematurely discontinued for lack of recruitement.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 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.
Giorgio La Nasa, MD principal investigator
Presidio Ospedaliero R. Binaghi, Cagliari - Italy
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 ITF2357 in people with Multiple Myeloma, 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 12 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: stopped early, as of the sponsor's last update on 2 Feb 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 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 was stopped early (reason given: The study was prematurely discontinued for lack of recruitement.). 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?
Number of patients with relapsing/refractory multiple myeloma with TEAE, included serious AE (time frame: 30 weeks). 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 2 Feb 2022.