Phase II High Pulse Dose Clinical Trial of Orally Administered ITF2357 In Patients With Relapsed/Refractory Multiple Myeloma

• Status: Terminated
• Trial end date: 2010-07-01

Summary

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:

Weeks 1-6

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.

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

Primary objective:

To assess the safety of ITF2357 administered once weekly at high pulse dose in patients with relapsing/refractory multiple myeloma.

• Phase: Phase 2

Details

• Lead Sponsor: Italfarmaco
• Treatments: Givinostat hydrochloride