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A phase II study in patients with low and intermediate -1 risk myelodysplastic syndrome while on therapy with deferasirox to investigate the presence of molecular factors in the baseline bone marrow which could predict an hematologic improvement due to therapy with deferasirox

Phase 1
Conditions
The study will include two groups of patients with low and intermediate 1 risk myelodysplastic syndrome. One group consists of patients who experience an hematological response while on deferasirox therapy while the other group consists of patients who are non-responders
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
Registration Number
EUCTR2015-003775-30-BE
Lead Sponsor
ovartis Pharma NV
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
Not specified
Inclusion Criteria

1. Written informed consent obtained prior to any other study procedure,
2. Males or females = 18 years of age,
3. MDS according to WHO criteria lasting = 14 weeks at the time of screening,
4. IPSS score <1.5 (low and intermediate-1 risk patients) at the time of screening using the IPSS score of 1997
5. Treatment with deferasirox:
- Only for the responder group: Treatment with deferasirox for prevention or treatment of IOL for at least 14 weeks before screening.
- Only for the non-responder group: Treatment with deferasirox for at least 9 months for prevention or treatment of IOL before screening to exclude patients with a late hematological response.
6. Only for responder-group: Patient with hematological response defined according to the IWG criteria of 2006 which must last at least 8 weeks and confirmed by the scientific advisory committee.
7. Only for non-responder group: confirmation by the scientific advisory committee that patient is eligible based on matched-pairing and confirmation of no hematological response. Minimal requirements for matched pairing include age, sex, IPSS score, hemoglobin level and transfusion need at baseline, treatment duration with deferasirox and time since MDS diagnosis. Pairing can be extended according to level of leukopenia, thrombocytopenia, serum ferritin level at baseline, comorbidities and transfusion history.
8.Bone marrow aspirate taken at the time of MDS diagnosis (at baseline) retrievable from patient’s hospital and viably frozen. This should be checked by the treating hematologist/oncologist before referring the patient for potential inclusion to the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
;
1. Written informed consent obtained prior to any other study procedure,
2. Males or females = 18 years of age,
3. MDS according to WHO criteria lasting = 14 weeks at the time of screening,
4. IPSS score <1.5 (low and intermediate-1 risk patients) at the time of screening using the IPSS score of 1997
5. Treatment with deferasirox:
- Only for the responder group: Treatment with deferasirox for prevention or treatment of IOL for at least 14 weeks before screening.
- Only for the non-responder group: Treatment with deferasirox for at least 9 months for prevention or treatment of IOL before screening to exclude patients with a late hematological response.
6. Only for responder-group: Patient with hematological response defined according to the IWG criteria of 2006 which must last at least 8 weeks and confirmed by the scientific advisory committee.
7. Only for non-responder group: confirmation by the scientific advisory committee that patient is eligible based on matched-pairing and confirmation of no hematological response. Minimal requirements for matched pairing include age, sex, IPSS score, hemoglobin level and transfusion need at baseline, treatment duration with deferasirox and time since MDS diagnosis. Pairing can be extended according to level of leukopenia, thrombocytopenia, serum ferritin level at baseline, comorbidities and transfusion history.
8.Bone marrow aspirate taken at the time of MDS diagnosis (at baseline) retrievable from patient’s hospital and viably frozen. This should be checked by the treating hematologist/oncologist before referring the patient for potential inclusion to the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
;
1. Written informed consent obtained prior to any other study procedure,
2. Males or females = 18 years of age,
3. MDS according to WHO criteria lasting = 14 weeks at the time of screening,
4. IPSS score <1.5 (low and intermediate-1 risk patients) at the time of screening using the IPSS score of 1997
5. Treatment with deferasirox:
- Only for the responder group: Treatment with deferasirox for prevention or treatment of IOL for at least 14 weeks before screening.
- Only for the non-responder group: Treatment with deferasirox for at least 9 months for prevention or treatment of IOL before screening to exclude patients with a late hematological response.
6. Only for responder-group: Patient with hematological response defined according to the IWG criteria of 2006 which must last at least 8 weeks and confirmed by the scientific advisory committee.
7. Only for non-responder group: confirmation by the scientific advisory committee that patient is eligible based on matched-pairing and confirmation of no hematological response. Minimal requirements for matched pairing include age, sex, IPSS score, hemoglobin level and transfusion need at baseline, treatment duration with deferasirox and time since MDS diagnosis. Pairing can be extended according to level of leukopenia, thrombocytopenia, serum ferritin level at baseline, comorbidities and transfusion history.
8.Bone marrow aspirate taken at the time of MDS diagnosis (at baseline) retrievable from patient’s hospital and viably frozen. This should be checked by the treating hematologist/oncologist before referring the patient for potential inclusion to the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1. Known concomitant presence of anemia due to iron, B12 or folate deficiencies, auto-immune or hereditary hemolysis, gastro-intestinal bleeding, or medication induced anemia at the time of screening,
2. Known infection with viral hepatitis B (HBV) or hepatitis C (HCV) defined as the presence in blood of HBV antigens in absence of HB antibodies, or presence of HCV antibodies at the time of screening,
3. Known positivity to human immunodeficiency virus (HIV) measured by enzyme-linked immunosorbent assay (ELISA) or western blot at the time of screening,
4. Patient participating in another clinical trial or receiving an investigational drug, within 1 month prior to study inclusion
5. History of other malignancy within the last five years, with the exception of basal skin carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ.
6. Concomitant treatment with other drugs known or suspected to elicit hematological response (azacitidine, erythroid stimulating agents, granulocyte colony stimulating factors, lenalidomide, thalidomide, valproate, ATG, cyclosporine, arsenic trioxide). When patients are still receiving red blood cell transfusions, patients are still eligible for study inclusion as long as they meet the IWG criteria of 2006
7. Female patients who are pregnant or breast feeding.

;
1. Known concomitant presence of anemia due to iron, B12 or folate deficiencies, auto-immune or hereditary hemolysis, gastro-intestinal bleeding, or medication induced anemia at the time of screening,
2. Known infection with viral hepatitis B (HBV) or hepatitis C (HCV) defined as the presence in blood of HBV antigens in absence of HB antibodies, or presence of HCV antibodies at the time of screening,
3. Known positivity to human immunodeficiency virus (HIV) measured by enzyme-linked immunosorbent assay (ELISA) or western blot at the time of screening,
4. Patient participating in another clinical trial or receiving an investigational drug, within 1 month prior to study inclusion
5. History of other malignancy within the last five years, with the exception of basal skin carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ.
6. Concomitant treatment with other drugs known or suspected to elicit hematological response (azacitidine, erythroid stimulating agents, granulocyte colony stimulating factors, lenalidomide, thalidomide, valproate, ATG, cyclosporine, arsenic trioxide). When patients are still receiving red blood cell transfusions, patients are still eligible for study inclusion as long as they meet the IWG criteria of 2006
7. Female patients who are pregnant or breast feeding.

;
1. Known concomitant presence of anemia due to iron, B12 or folate deficiencies, auto-immune or hereditary hemolysis, gastro-intestinal bleeding, or medication induced anemia at the time of screening,
2. Known infection with viral hepatitis B (HBV) or hepatitis C (HCV) defined as the presence in blood of HBV antigens in absence of HB antibodies, or presence of HCV antibodies at the time of screening,
3. Known positivity to human immunodeficiency virus (HIV) measured by enzyme-linked immunosorbent assay (ELISA) or western blot at the time of screening,
4. Patient participating in another clinical trial or receiving an investigational drug, within 1 month prior to study inclusion
5. History of other malignancy within the last five years, with the exception of basal skin carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ.
6. Concomitant treatment with other drugs known or suspected to elicit hematological response (azacitidine, erythroid stimulating agents, granulocyte colony stimulating factors, lenalidomide, thalidomide, valproate, ATG, cyclosporine, arsenic trioxide). When patients are still receiving red blood cell transfusions, patients are still eligible for study inclusion as long as they meet the IWG criteria of 2006
7. Female patients who are pregnant or breast feeding.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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