Post Hematopoietic Stem Cell Transplantation
Study Details
Study Description
Brief Summary
This was a prospective, single-arm, multicenter, national, phase II clinical study. The purpose of this Phase II study was to examine the safety and efficacy of deferasirox to decrease iron overload (IOL) in the posttransplant period in patients with beta-thalassemia major.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ICL670 Oral dose of ICL670 at 10 mg/kg daily |
Drug: ICL670
Oral dose of ICL670 at 10 mg/kg daily
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events, Serious Adverse Events and Deaths as a Measure of Safety and Tolerability [12 months]
To determine the safety; incidence, type and severity of adverse events including renal, hepatic, biochemistry and hematologic parameters of deferasirox in the treatment of iron overload after hematopoietic stem cell transplantation (HSCT) in patients with beta-thalassemia major in 12 months period
Secondary Outcome Measures
- Change in Serum Ferritin Level. [Baseline, 12 Months]
Blood samples were collected and serum levels were assessed at study baseline (BL) and at 12 months.
- Change in the Further Parameters of Iron Overload (Liver Iron Concentration by Magnetic Resonance Imaging (MRI Examination) [Baseline, 12 month]
Liver Iron Concentration (LIC) values between 3 and 7 mg Fe / g dry weight are indicative of mild iron deposition, while values between 7 and 15 mg Fe / g dry weight are indicative of moderate iron deposition which have been associated with liver disease. Values >15 mg Fe/g dry weight are indicative of severe iron deposition which is associated with progressive liver fibrosis, increased morbidity and mortality
- The Percentage of Patients Reaching Serum Ferritin Levels Lower Than 500 μg/L [Week 28 and Week 52]
Serum Ferritin values between 1000-2500 μg/L are indicative of mild to moderate iron overload while values >2500 μg/L are indicative of severe iron overload and levels constantly higher than 2500 μg/L has been shown to to increase the risk of cardiac complications and endocrine disease. Maintaining levels <1000 μg/L is associated with increased survival and less morbidity.
- Change in the Further Parameters of Iron Overload (Cardiac Iron Concentration by Magnetic Resonance Imaging (MRI Examination) [Baseline, 12 month]
Cardiac MRI values between 10 to 20 milliseconds (ms) are indicative of moderate cardiac iron deposition associated with declining left ventricular ejection fraction and arrhythmias while values <10 ms are indicative of deposition sufficient to risk cardiac decompensation and associated with overt heart failure and mortality.
Eligibility Criteria
Criteria
Inclusion Criteria
-
Patients who had hematopoietic stem cell transplantation (HSCT) for beta-thalassemia major
-
hematopoietic stem cell transplantation (HSCT) was performed minimum 6 months and maximum 2 years ago
-
The washout period after the immunosuppressive therapy should be at least 3 months.
-
Signifacant IOL should be present including:
- Serum ferritin >1000 μg/L or B. cardiac MRI <20 ms or C. liver iron concentration ≥ 5 mg/g dry weight measured by R2* MRI
Exclusion Criteria
- Patients who had any contraindication for treatment with deferasirox according to the prescribing information
•Patients who depended on transfusion
-
Patients with clinical symptoms of cardiac dysfunction (shortness of breath at rest or exertion, orthopnea, exercise intolerance, lower extremity edema, arrhythmias)
-
Patients who were experiencing severe complication of HSCT e.g. acute Graft-versus host disease (GVHD)
-
Significant proteinuria / Increase in serum creatinine
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Ankara | Turkey | 06100 | |
| 2 | Novartis Investigative Site | Ankara | Turkey | 06500 | |
| 3 | Novartis Investigative Site | Antalya | Turkey | 07000 | |
| 4 | Novartis Investigative Site | Antalya | Turkey | 07070 | |
| 5 | Novartis Investigative Site | Istanbul | Turkey | ||
| 6 | Novartis Investigative Site | Izmir | Turkey | 35040 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CICL670ATR04
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | ICL670 |
|---|---|
| Arm/Group Description | Oral dose of ICL670 at 10 mg/kg daily |
| Period Title: Overall Study | |
| STARTED | 27 |
| COMPLETED | 26 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | ICL670 |
|---|---|
| Arm/Group Description | Oral dose of ICL670 at 10 mg/kg daily |
| Overall Participants | 27 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
9.07
(3.81)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
8
29.6%
|
| Male |
19
70.4%
|
Outcome Measures
| Title | Number of Participants With Adverse Events, Serious Adverse Events and Deaths as a Measure of Safety and Tolerability |
|---|---|
| Description | To determine the safety; incidence, type and severity of adverse events including renal, hepatic, biochemistry and hematologic parameters of deferasirox in the treatment of iron overload after hematopoietic stem cell transplantation (HSCT) in patients with beta-thalassemia major in 12 months period |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Set (SS) includes all included patients who were included in the study. All statistical analyses of safety and tolerability will be done in the SS. |
| Arm/Group Title | ICL670 |
|---|---|
| Arm/Group Description | Oral dose of ICL670 at 10 mg/kg daily |
| Measure Participants | 27 |
| Adverse events |
25
92.6%
|
| Serious adverse events |
3
11.1%
|
| Death |
0
0%
|
| Title | Change in Serum Ferritin Level. |
|---|---|
| Description | Blood samples were collected and serum levels were assessed at study baseline (BL) and at 12 months. |
| Time Frame | Baseline, 12 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set (FAS) comprises all patients in whom study treatment has been started and received at least one dose. |
| Arm/Group Title | ICL670 |
|---|---|
| Arm/Group Description | Oral dose of ICL670 at 10 mg/kg daily |
| Measure Participants | 27 |
| Baseline |
1766.81
(599.64)
|
| Month 12 |
903.56
(596.62)
|
| Title | Change in the Further Parameters of Iron Overload (Liver Iron Concentration by Magnetic Resonance Imaging (MRI Examination) |
|---|---|
| Description | Liver Iron Concentration (LIC) values between 3 and 7 mg Fe / g dry weight are indicative of mild iron deposition, while values between 7 and 15 mg Fe / g dry weight are indicative of moderate iron deposition which have been associated with liver disease. Values >15 mg Fe/g dry weight are indicative of severe iron deposition which is associated with progressive liver fibrosis, increased morbidity and mortality |
| Time Frame | Baseline, 12 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set (FAS) comprises all patients in whom study treatment has been started and received at least one dose. |
| Arm/Group Title | ICL670 |
|---|---|
| Arm/Group Description | Oral dose of ICL670 at 10 mg/kg daily |
| Measure Participants | 27 |
| Baseline Liver MRI(n= 27) |
12.07
(9.42)
|
| Week 52 Liver MRI (n=25) |
4.62
(2.85)
|
| Title | The Percentage of Patients Reaching Serum Ferritin Levels Lower Than 500 μg/L |
|---|---|
| Description | Serum Ferritin values between 1000-2500 μg/L are indicative of mild to moderate iron overload while values >2500 μg/L are indicative of severe iron overload and levels constantly higher than 2500 μg/L has been shown to to increase the risk of cardiac complications and endocrine disease. Maintaining levels <1000 μg/L is associated with increased survival and less morbidity. |
| Time Frame | Week 28 and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set (FAS) comprises all patients in whom study treatment has been started and received at least one dose. |
| Arm/Group Title | ICL670 |
|---|---|
| Arm/Group Description | Oral dose of ICL670 at 10 mg/kg daily |
| Measure Participants | 27 |
| Week 28 (n=26) |
7.7
|
| Week 52 (n=27) |
33.3
|
| Title | Change in the Further Parameters of Iron Overload (Cardiac Iron Concentration by Magnetic Resonance Imaging (MRI Examination) |
|---|---|
| Description | Cardiac MRI values between 10 to 20 milliseconds (ms) are indicative of moderate cardiac iron deposition associated with declining left ventricular ejection fraction and arrhythmias while values <10 ms are indicative of deposition sufficient to risk cardiac decompensation and associated with overt heart failure and mortality. |
| Time Frame | Baseline, 12 month |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set (FAS) comprises all patients in whom study treatment has been started and received at least one dose. |
| Arm/Group Title | ICL670 |
|---|---|
| Arm/Group Description | Oral dose of ICL670 at 10 mg/kg daily |
| Measure Participants | 27 |
| Baseline Cardiac MRI(n= 27) |
26.48
(7.49)
|
| Week 52 Cardiac MRI (n=24) |
28.25
(5.53)
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | ICL670 | |
| Arm/Group Description | Oral dose of ICL670 at 10 mg/kg daily | |
All Cause Mortality |
||
| ICL670 | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| ICL670 | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/27 (11.1%) | |
| General disorders | ||
| Influenza like illness | 1/27 (3.7%) | |
| Hepatobiliary disorders | ||
| Hepatitis B | 1/27 (3.7%) | |
| Investigations | ||
| Neutrophil count decreased | 2/27 (7.4%) | |
| Alanine aminotransferase increased | 1/27 (3.7%) | |
| Aspartate aminotransferase increased | 1/27 (3.7%) | |
| Surgical and medical procedures | ||
| Office visit | 1/27 (3.7%) | |
Other (Not Including Serious) Adverse Events |
||
| ICL670 | ||
| Affected / at Risk (%) | # Events | |
| Total | 23/27 (85.2%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 7/27 (25.9%) | |
| Gastrointestinal disorders | ||
| Diarrhea | 3/27 (11.1%) | |
| Vomiting | 3/27 (11.1%) | |
| General disorders | ||
| Pyrexia | 7/27 (25.9%) | |
| Influenza like illness | 2/27 (7.4%) | |
| Immune system disorders | ||
| Hypersensitivity | 2/27 (7.4%) | |
| Infections and infestations | ||
| Pharyngitis | 6/27 (22.2%) | |
| Haemophilus infection | 2/27 (7.4%) | |
| Herpes zoster | 2/27 (7.4%) | |
| Infection | 2/27 (7.4%) | |
| Sinusitis | 2/27 (7.4%) | |
| Investigations | ||
| Aspartate aminotransferase increased | 6/27 (22.2%) | |
| White blood cell count decreased | 2/27 (7.4%) | |
| Alanine aminotransferase increased | 7/27 (25.9%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 7/27 (25.9%) | |
| Influenza | 5/27 (18.5%) | |
| Upper respiratory tract infection | 2/27 (7.4%) | |
| Rhinorrhea | 2/27 (7.4%) | |
| Skin and subcutaneous tissue disorders | ||
| Eczema | 2/27 (7.4%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis |
| Phone | 862-778-8300 |
- CICL670ATR04