Overview

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
Target enrollment:
0
Participant gender:
All
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
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Italfarmaco
Treatments:
Givinostat hydrochloride
Criteria
Inclusion Criteria:

1. Established diagnosis of multiple myeloma according to International Myeloma Working
Group diagnostic criteria

2. Age ≥ 18 years

3. 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

4. Increasing trend of monoclonal immunoglobulin or Bence-Jones proteinuria through the
last 4 consecutive pre-screening measurements, already available in the patient
history

5. No chemotherapy or other investigational anticancer therapy for at least 3 weeks
before the start of the study

6. Full recovery from previous toxicities

7. ECOG performance status 0-2

8. Adequate bone marrow reserve: absolute neutrophil count ≥ 1000/ml; platelet count ≥
90000/ml

9. 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)

10. Adequate renal function: Creatinine ≤ 2.5 mg/dl or creatinine clearance ≥ 50 ml/min

11. 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

12. Able to understand and willing to sign the informed consent form.

Exclusion Criteria:

1. Planned autologous or allogeneic bone marrow transplantation within 4 weeks of the
initiation of ITF 2357 administration

2. Concurrent use of medicines that would confound the interpretation of toxicities and
anti-tumour activity of ITF 2357 (i.e. quinolons, macrolides, 5-HT3 antagonists except
for palonosetron,)

3. 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

4. Psychiatric illness/social situations that would limit compliance with study
medication and protocol requirements

5. Pregnant or lactating women

6. Positive blood tests for HIV, HBV, HCV, active EBV and CMV

7. Diseases related to active viral infections

8. 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)

9. Patients with history of additional risk factors for Torsade de Pointes (e.g. heart
failure, family history of Long QT Syndrome).

10. The use of concomitant medications with potential risk of Torsade de Pointes and/or
that can prolong QTc interval

-