Trial Outcomes & Findings for Trial of the Histone-Deacetylase Inhibitor ITF2357 Followed by Mechlorethamine in Relapsed/Refractory Hodgkin's Lymphoma (NCT NCT00792467)
NCT ID: NCT00792467
Last Updated: 2021-05-11
Results Overview
OR rate among patients treated is defined according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group. In medicine, a response rate is the percentage of patients whose cancer shrinks or disappears after treatment. The FDA definition of ORR is the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. The tumor objective response rate (ORR) is an important parameter to demonstrate the efficacy of a treatment in oncology. The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials.
COMPLETED
PHASE1/PHASE2
24 participants
At each 21-day cycle for a maximum of 12 cycles
2021-05-11
Participant Flow
Patients enrolled were 24 subjects of both genders, age ≥18 years, with histologically confirmed diagnosis of Hodgkin's lymphoma and refractory or relapsed.
Participant milestones
| Measure |
ITF2357
Patients received the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
|---|---|
|
Overall Study
STARTED
|
24
|
|
Overall Study
COMPLETED
|
2
|
|
Overall Study
NOT COMPLETED
|
22
|
Reasons for withdrawal
| Measure |
ITF2357
Patients received the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
|---|---|
|
Overall Study
progression of disease
|
17
|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
patient request
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Patient achieved a PR and allogenic transplant was performed
|
1
|
|
Overall Study
Patient in CR and HLA-matched donor available. Allogenic SCT performed
|
1
|
Baseline Characteristics
Trial of the Histone-Deacetylase Inhibitor ITF2357 Followed by Mechlorethamine in Relapsed/Refractory Hodgkin's Lymphoma
Baseline characteristics by cohort
| Measure |
ITF2357
n=24 Participants
Patients will receive the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy will be administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
24 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
35.83 years
STANDARD_DEVIATION 14.49 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At each 21-day cycle for a maximum of 12 cyclesPopulation: Intent-to-treat population: all patients valid for Safety population. Per Protocol population: all recruited patients who: 1) were not severe protocol violators; 2) had at least one on-study tumor assessment beside baseline; 3) experienced disease progression or, if not, received at least 2 cycles of the study treatment consecutively.
OR rate among patients treated is defined according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group. In medicine, a response rate is the percentage of patients whose cancer shrinks or disappears after treatment. The FDA definition of ORR is the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. The tumor objective response rate (ORR) is an important parameter to demonstrate the efficacy of a treatment in oncology. The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials.
Outcome measures
| Measure |
ITT Population
n=24 Participants
Patients received the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
PP Population
n=16 Participants
Patients received the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
|---|---|---|
|
Objective Response Rate (ORR)
Objective Response achieved
|
25.00 percentage of patients
|
37.50 percentage of patients
|
|
Objective Response Rate (ORR)
Objective Response not achieved
|
75.00 percentage of patients
|
62.50 percentage of patients
|
PRIMARY outcome
Timeframe: At each 21-day cycle for a maximum of 12 cyclesPopulation: Intent-to-treat population: all patients valid for Safety population. Per Protocol population: all recruited patients who: 1) were not severe protocol violators; 2) had at least one on-study tumor assessment beside baseline; 3) experienced disease progression or, if not, received at least 2 cycles of the study treatment consecutively.
Complete responder (CR) and partial responder (PR) among patients treated are defined according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group. CR is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR is defined as regression of measurable disease and no new sites. The frequencies of patients achieving objective response (i.e. subjects whose best overall response was CR or PR) and the frequencies of patients who did not achieve an objective response (i.e.subjects whose best overall response was equal to stable disease - SD, progressive disease - PD - or not evaluable) in ITT and PP populations are reported. NED= no evidence of disease
Outcome measures
| Measure |
ITT Population
n=24 Participants
Patients received the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
PP Population
n=16 Participants
Patients received the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
|---|---|---|
|
Proportion of Responders (Complete -CR- or Partial PR-)
Not evaluable
|
8.33 percentage of participants
|
0 percentage of participants
|
|
Proportion of Responders (Complete -CR- or Partial PR-)
CR/NED
|
4.17 percentage of participants
|
6.25 percentage of participants
|
|
Proportion of Responders (Complete -CR- or Partial PR-)
PR
|
20.83 percentage of participants
|
31.25 percentage of participants
|
|
Proportion of Responders (Complete -CR- or Partial PR-)
SD
|
29.17 percentage of participants
|
25.00 percentage of participants
|
|
Proportion of Responders (Complete -CR- or Partial PR-)
PD
|
37.50 percentage of participants
|
37.50 percentage of participants
|
SECONDARY outcome
Timeframe: From the first day of the first cycle of treatment until objective tumor progression or death, whichever came first, assessed up to 450 days from the start of the first cycle of treatmentPopulation: Intent-to-treat population: all patients valid for Safety population. Per Protocol population: all recruited patients who: 1) were not severe protocol violators; 2) had at least one on-study tumor assessment beside baseline; 3) experienced disease progression or, if not, received at least 2 cycles of the study treatment consecutively.
PFS is defined as the time from the 1st day of the 1st cycle of treatment until objective tumor progression or death. It included deaths, thus could be correlated to overall survival. If a patient did not have disease progression, PFS was censored at the date of last available tumor assessment (including those at end of study or follow-up visit).
Outcome measures
| Measure |
ITT Population
n=24 Participants
Patients received the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
PP Population
n=16 Participants
Patients received the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
|---|---|---|
|
Progression-Free Survival (PFS)
|
164.53 Days
Standard Deviation 28.66
|
183.94 Days
Standard Deviation 39.38
|
SECONDARY outcome
Timeframe: From the first day of the first cycle until the date of achieving a response assessed up to 250 days from the start of the first cycle of treatmentPopulation: Intent-to-treat population: all patients valid for Safety population. Per Protocol population: all recruited patients who: 1) were not severe protocol violators; 2) had at least one on-study tumor assessment beside baseline; 3) experienced disease progression or, if not, received at least 2 cycles of the study treatment consecutively.
TTR is defined as the time from the 1st day of the 1st cycle until the date of achieving a response (CR or PR). In case of no objective response, TTR was censored at the date of last available tumor assessment (including those at end of study or follow-up visit).
Outcome measures
| Measure |
ITT Population
n=24 Participants
Patients received the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
PP Population
n=16 Participants
Patients received the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
|---|---|---|
|
Time To Response (TTR)
|
123.52 Days
Standard Deviation 11.70
|
114.34 Days
Standard Deviation 14.81
|
SECONDARY outcome
Timeframe: From the first day of the first cycle of treatment until objective tumor progression or death, whichever came first, or last available tumor assessment (assessed up to 350 days from the start of the first cycle of treatment).Population: Intent-to-treat population: all patients valid for Safety population. Per Protocol population: all recruited patients who: 1) were not severe protocol violators; 2) had at least one on-study tumor assessment beside baseline; 3) experienced disease progression or, if not, received at least 2 cycles of the study treatment consecutively.
Duration of objective response (CR or PR) was applied only to patients whose best overall response was CR or PR.
Outcome measures
| Measure |
ITT Population
n=6 Participants
Patients received the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
PP Population
n=6 Participants
Patients received the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
|---|---|---|
|
Response Duration (RD):
|
199.96 Days
Standard Deviation 42.77
|
199.96 Days
Standard Deviation 42.77
|
Adverse Events
ITF2357
Serious adverse events
| Measure |
ITF2357
n=24 participants at risk
Patients will receive the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy will be administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.2%
1/24 • Number of events 1 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.2%
1/24 • Number of events 1 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Fever
|
4.2%
1/24 • Number of events 1 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
Other adverse events
| Measure |
ITF2357
n=24 participants at risk
Patients will receive the following therapy cycle
* ITF2357, 50 mg every 6 hours, per os, days 1 - 3;
* Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy will be administered every 21 days as long as there is no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles.
ITF2357: ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
50.0%
12/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Cardiac disorders
Leukopenia
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Cardiac disorders
Neutropenia
|
45.8%
11/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Cardiac disorders
Thrombocytopenia
|
66.7%
16/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Cardiac disorders
Atrial fibrillation
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Gastrointestinal disorders
Abdominal pain
|
8.3%
2/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Gastrointestinal disorders
Diarrhoea
|
20.8%
5/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Gastrointestinal disorders
Dysphagia
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Gastrointestinal disorders
Nausea
|
29.2%
7/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Gastrointestinal disorders
Stomatitis
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Gastrointestinal disorders
Vomiting
|
20.8%
5/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
General disorders
Asthenia
|
25.0%
6/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
General disorders
chest pain
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
General disorders
Extravasation
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
General disorders
Fatigue
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
General disorders
Injection site reaction
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
General disorders
Pyrexia
|
29.2%
7/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Immune system disorders
Graft versus host disease
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Infections and infestations
Infection
|
8.3%
2/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Infections and infestations
Skin infection
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Infections and infestations
Upper respiratory tract infection
|
12.5%
3/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Investigations
Alanine aminotransferase increased
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Investigations
Aspartate aminotransferase increased
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Investigations
Platelet count decreased
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Metabolism and nutrition disorders
Anorexia
|
8.3%
2/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Nervous system disorders
Headache
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.0%
6/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.8%
5/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
12.5%
3/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal inflammation
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
12.5%
3/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Skin and subcutaneous tissue disorders
Butterfly rash
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.3%
2/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
|
Vascular disorders
Deep vein thrombosis
|
4.2%
1/24 • Throughout the course of the study, up to a maximum of 12 cycles, an average of 1 year.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place