Phase II High Pulse Dose Clinical Trial of Orally Administered ITF2357 In Patients With Relapsed/Refractory Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT00792506|
Recruitment Status : Terminated
First Posted : November 18, 2008
Last Update Posted : May 24, 2013
This is open label, phase IIa High Pulse Dose Clinical Trial testing ITF2357 (orally administration)in adult patients with relapsing/refractory multiple myeloma after at least 2 previous lines of treatment.
Patients will receive ITF2357 in accordance with following scheme:
Patient #01 will be administered ITF 2357 at 400 mg in one single dose on day 1, 8, 15, 22, 29 and 36. Safety assessments will 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.
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.
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
To assess the safety of ITF2357 administered once weekly at high pulse dose in patients with relapsing/refractory multiple myeloma.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: ITF2357||Phase 2|
Multiple myeloma (MM) is a B-cell neoplasm that manifests as one or more lytic bone lesions, monoclonal protein in the blood or urine and disease in the bone marrow (BM). The malignant plasma cells accumulate in the BM and intricate interactions occur between the BM microenvironment and the MM cells, frequently causing bone destruction, which in turn stimulates tumour growth. The tumour itself, its products and the host response to it result in the multitude of symptoms and organ dysfunction characteristic of MM, including bone pain, renal failure, susceptibility to infections, anaemia and hypercalcemia. The median age at diagnosis is 68 years and men are more frequently affected than women.
ITF2357 is a novel and proprietary molecule synthesized by Italfarmaco S.p.A. Research Laboratories, provided with an established and powerful HDAC-inhibitory activity. It is being developend for a range of possible clinical applications both in oncohaematological conditions and in chronic inflammatory diseases. The former application is consistent with the well known antitumor pharmacological properties of HDAC-inhibitors as a family (i.e. cell-cycle arrest, pro-apoptotic and cell-differentiating effects); the latter application (chronic inflammation) is based of the demonstrated anticytokine effect of ITF2357.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II High Pulse Dose Clinical Trial of Orally Administered ITF2357 In Patients With Relapsed/Refractory Multiple Myeloma|
|Study Start Date :||October 2008|
|Actual Primary Completion Date :||January 2010|
|Actual Study Completion Date :||July 2010|
Treatment was to be administered on an inpatient basis from week 1 to week 13 and on an outpatient basis from week 14 to end of treatment. The patient 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.
Other Name: Histone-Deacetylase Inibitor
- To assess the safety of ITF2357 administered once weekly at high pulse dose in patients with relapsing/refractory multiple myeloma. [ Time Frame: 30 weeks ]
- 1. 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. [ Time Frame: 18 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00792506
|Presidio Ospedaliero R. Binaghi|
|Cagliari, Italy, 09127|
|Principal Investigator:||Giorgio La Nasa, MD||Presidio Ospedaliero R. Binaghi, Cagliari - Italy|