Bone Marrow DiseasesPhase 2NCT00113893
SCIO-469: Open-Label Study for Patients With Myelodysplastic Syndromes.
A Phase 2 study testing SCIO-469 in people with Bone Marrow Diseases and Myelodysplastic Syndromes, run by Scios, Inc..
Trial summary
The purpose of this study is to determine the safety and effectiveness of oral SCIO-469 in patients with myelodysplastic syndromes. SCIO-469 belongs to a new class of treatments that inhibit expression and activity of cytokines that play a role in the progression of MDS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bone Marrow Diseases, Myelodysplastic Syndromes, Hematologic Diseases
- What is being tested?
- SCIO-469
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- No sites listed yet
- Study dates
- May 2005to Dec 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with a diagnosis of low/intermediate-1 MDS (for at least 12 weeks)
- Patients with anemia (average Hemoglobin < 10 g/dL or > or = to 4 units of Red Blood Cell counts in the last 8 weeks)
- Patients who have failed prior erythropoietin treatment
- Patients with an ECOG (Eastern Collaborative Oncology Group) score of 0, 1 or 2
Who cannot join
- Patients with a International Prognostic Scoring System risk category high/intermediate-2
- Patients with treatment-related MDS associated with radiation, chemotherapy, and/or autologous transplant
- Patients with myelosclerosis (or myelofibrosis) occupying > 30 % marrow space
- Patients who have received decitabine (DacogenTM) for MDS
- Patients who have received lenalidomide (RevlimidTM), steroids, erythropoietin, hydroxyurea, or growth factors within 4 weeks before study drug administration
- Patients who have received thalidomide within 8 weeks before study drug administration
About this study
Official title: A Randomized, MultiCenter, Open-Label, Modified Dose-Ascension, Parallel Study of the Safety, Tolerability, and Efficacy of Oral SCIO-469 in Patients With Myelodysplastic Syndromes
The purpose of this study is to determine the safety and effectiveness of oral SCIO-469 in patients with myelodysplastic syndromes. SCIO-469 belongs to a new class of treatments that inhibit expression and activity of cytokines that play a role in the progression of MDS.
Read the detailed description
SCIO-469 belongs to a new class of treatment that inhibits p38 MAP kinase. p38 MAPK activation controls the production of TNF-a, VEGF, and IL-1b. As an inhibitor of p38 MAPK, SCIO-469 blocks the synthesis of these molecules, as well as TNF-a activity. This randomized, open-label, modified dose-ascension study is designed to assess the safety, tolerability, and efficacy of oral SCIO-469 in the treatment of patients with MDS. This patient group was selected because of the inhibitory effect of SCIO-469 on the expression and activity of cytokines that play a role in the progression of MDS. The treatment arms will be 30, 60 , 90, or 120 mg tid with 15 subjects per arm (total of 60 subjects) and each arm may expand to 25 subjects per arm (maximum total of 100 subjects). Initially, subjects will be randomly assigned to one of the lowest two treatment arms (30 mg tid or 60 mg tid). When 6 subjects per arm (at least 12 subjects total) have received study drug for at least 4 weeks, predefined criteria will be used to determine whether to open randomization into the third arm (i.e., 90 mg tid). The criteria will be based on the number of subjects who have had to suspend study drug due to drug-related toxicity. The 120-mg tid arm will be open for enrollment after 15 subjects have been enrolled into each of the first three treatment arms; the decision to open enrollment will be similar to the criteria used to open the third arm. Subjects will be evaluated at least monthly for safety and some efficacy measurements (AE reporting, safety labs and vitals). Subjects will receive study drug for 16 weeks. Subjects who demonstrate hematologic improvement (erythroid, platelet, or neutrophil response by IWG criteria) at week 16 will be eligible to continue treatment at the same dose of study drug for up to 36 additional weeks (52 weeks of total drug exposure). Subjects who do not meet the IWG criteria for hematologic improvement at week 16 but who, in the judgment of the investigator, experience clinical benefit may also receive up to 36 additional weeks of treatment. The same judgments for treatment extensions of additional 26 weeks in responding subjects will be made at 52 weeks and 78 weeks; maximum total drug exposure will be 104 weeks. All subjects will be followed for 4 weeks after the last study drug treatment for safety assessments or until resolution of Grade 3 or greater treatment-related toxicity as defined by NCI CTCAE (v. 3.0).
Oral SCIO-469 given for 16 weeks to patients with MDS. Subjects will receive a total daily dose of SCIO-469 of 90 mg, 180 mg, 270 mg, or 360 mg. The treatment arms will be 30-mg tablet tid, 60-mg tablet tid, 90-mg tablet tid, or 120 mg (i.e., two 60-mg tablets) tid with 15 subjects per arm (total of 60 subjects). Responding subjects may dose for up to 104 weeks total drug exposure.
- Conditions
- Bone Marrow Diseases, Myelodysplastic Syndromes, Hematologic Diseases, Bone Marrow Neoplasms
- Being tested
- SCIO-469
- Keywords
- Myelodysplastic syndromes, p38 MAP kinase, Bone marrow diseases, SCIO-469
- Medical subject headings
- Bone Marrow Diseases, Myelodysplastic Syndromes, Hematologic Diseases, Bone Marrow Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SCIO-469Drug
SCIO-469 tablet will be administered orally at a dose of 30 mg thrice daily (90 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks.
SCIO-469Drug
SCIO-469 tablet will be administered orally at a dose of 60 mg thrice daily (180 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks.
SCIO-469Drug
SCIO-469 tablet will be administered orally at a dose of 90 mg thrice daily (270 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks.
SCIO-469Drug
SCIO-469 tablet will be administered orally at a dose of 120 mg thrice daily (360 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Scio-469 30 Milligram (mg) | Experimental | SCIO-469 tablet will be administered orally at a dose of 30 mg thrice daily (90 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks. Receives: Drug: SCIO-469 |
| Scio-469 60 mg | Experimental | SCIO-469 tablet will be administered orally at a dose of 60 mg thrice daily (180 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks. Receives: Drug: SCIO-469 |
| Scio-469 90 mg | Experimental | SCIO-469 tablet will be administered orally at a dose of 90 mg thrice daily (270 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks. Receives: Drug: SCIO-469 |
| Scio-469 120 mg | Experimental | SCIO-469 tablet will be administered orally at a dose of 120 mg thrice daily (360 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks. Receives: Drug: SCIO-469 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Major or Minor Erythroid Response (Hematological Improvement - Erythroid [HI-E])
Improvement in Erythroid (HI-E) lineage will be assessed as per International Working Group (IWG) criteria. HI-E major response is defined as greater than 2.0 gram per deciliter g/dL increase in hemoglobin for red blood cell (RBC) transfusion-dependent participants, transfusion independence. HI-E minor response is defined as 1.0 to 2.0 g/dL increase in hemoglobin for RBC transfusion-dependent participants and 50 percent decrease in transfusion requirements.
Measured: Week 16
Secondary outcomes (4)
Percentage of Participants Achieving Major or Minor Neutrophil Response (HI-N)
Major or minor neutrophils response is Hematologic Improvement in Neutrophil (HI-N) lineage. It will be assessed as per International Working Group (IWG) criteria. HI-N major response is defined as for participants with pre-treatment Absolute Neutrophil Count (ANC) less than 1500 per micro (l), at least 100 percent increase or an absolute increase more than 500 per micro l, whichever is greater. HI-N minor response defined as for participants with pre-treatment ANC less than 1500 per micro l, ANC increase of at least 100 percent, but with absolute increase less than 500 per micro l.
Measured: Week 16
Percentage of Participants Achieving Major or Minor Platelet Response (HI-P)
Major or minor neutrophils response is Hematologic Improvement in Platelets (HI-P) lineage. It will be assessed as per International Working Group (IWG) criteria. HI-P major response is defined as for participants with pre-treatment platelet count less than 100,000 per micro liter (l ), an absolute increase of 30,000 micro l or more. HI-P minor response defined as for participants with pre-treatment platelet count less than 100,000 per micro l, a 50 percent or more increase in platelet count with net increase greater than 10,000 per micro l but less than 30,000 per micro l.
Measured: Week 16
Percentage of Participants Achieving Complete or Partial Bone Marrow (BM) Response
Bone marrow response will be assessed as per the IWG criteria. Bone marrow response categories are: complete remission and partial remission. Complete remission is defined as normal bone marrow morphology (less than 5 percent myeloblasts with no cytologic dysplasia). Partial remission is defined as (must last at least 8 weeks) blasts decreased by 50 percent or more over pre-treatment, or a less advanced Myelodysplastic syndrome (MDS) French-American and British (FAB) classification than pre-treatment
Measured: Week 16
Percentage of Participants Achieving Major or Minor Cytogenetic Response
Cytogenetic response will be assessed as per IWG criteria. Major response is defined as no detectable cytogenetic abnormality, if pre-existing abnormality was present. Minor response is defined as greater than percent 50 reductions in abnormal metaphases.
Measured: Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2005 (estimated)
- Study startMay 2005
- Primary completionDec 2007
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bone Marrow DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Scios, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Scios, Inc. Clinical Trial, Study director, Scios, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00113893
- Sponsor's protocol ID
- CR005179
- Status last verified
- Oct 2013
- First submitted
- 10 Jun 2005
- Last updated
- 7 Nov 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, MultiCenter, Open-Label, Modified Dose-Ascension, Parallel Study of the Safety, Tolerability, and Efficacy of Oral SCIO-469 in Patients With Myelodysplastic Syndromes
- ClinicalTrials.gov ID
- NCT00113893
- Acronym / sponsor ID
- CR005179
- Conditions
- Bone Marrow Diseases, Myelodysplastic Syndromes, Hematologic Diseases, Bone Marrow Neoplasms
- Keywords
- Myelodysplastic syndromes, p38 MAP kinase, Bone marrow diseases, SCIO-469
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Scios, Inc.Industry (pharma, biotech, devices)
- Study start
- May 2005
- Primary completion
- Dec 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 13 Jun 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the safety and effectiveness of oral SCIO-469 in patients with myelodysplastic syndromes. SCIO-469 belongs to a new class of treatments that inhibit expression and activity of cytokines that play a role in the progression of MDS.
Detailed description
SCIO-469 belongs to a new class of treatment that inhibits p38 MAP kinase. p38 MAPK activation controls the production of TNF-a, VEGF, and IL-1b. As an inhibitor of p38 MAPK, SCIO-469 blocks the synthesis of these molecules, as well as TNF-a activity. This randomized, open-label, modified dose-ascension study is designed to assess the safety, tolerability, and efficacy of oral SCIO-469 in the treatment of patients with MDS. This patient group was selected because of the inhibitory effect of SCIO-469 on the expression and activity of cytokines that play a role in the progression of MDS. The treatment arms will be 30, 60 , 90, or 120 mg tid with 15 subjects per arm (total of 60 subjects) and each arm may expand to 25 subjects per arm (maximum total of 100 subjects). Initially, subjects will be randomly assigned to one of the lowest two treatment arms (30 mg tid or 60 mg tid). When 6 subjects per arm (at least 12 subjects total) have received study drug for at least 4 weeks, predefined criteria will be used to determine whether to open randomization into the third arm (i.e., 90 mg tid). The criteria will be based on the number of subjects who have had to suspend study drug due to drug-related toxicity. The 120-mg tid arm will be open for enrollment after 15 subjects have been enrolled into each of the first three treatment arms; the decision to open enrollment will be similar to the criteria used to open the third arm. Subjects will be evaluated at least monthly for safety and some efficacy measurements (AE reporting, safety labs and vitals). Subjects will receive study drug for 16 weeks. Subjects who demonstrate hematologic improvement (erythroid, platelet, or neutrophil response by IWG criteria) at week 16 will be eligible to continue treatment at the same dose of study drug for up to 36 additional weeks (52 weeks of total drug exposure). Subjects who do not meet the IWG criteria for hematologic improvement at week 16 but who, in the judgment of the investigator, experience clinical benefit may also receive up to 36 additional weeks of treatment. The same judgments for treatment extensions of additional 26 weeks in responding subjects will be made at 52 weeks and 78 weeks; maximum total drug exposure will be 104 weeks. All subjects will be followed for 4 weeks after the last study drug treatment for safety assessments or until resolution of Grade 3 or greater treatment-related toxicity as defined by NCI CTCAE (v. 3.0).
Oral SCIO-469 given for 16 weeks to patients with MDS. Subjects will receive a total daily dose of SCIO-469 of 90 mg, 180 mg, 270 mg, or 360 mg. The treatment arms will be 30-mg tablet tid, 60-mg tablet tid, 90-mg tablet tid, or 120 mg (i.e., two 60-mg tablets) tid with 15 subjects per arm (total of 60 subjects). Responding subjects may dose for up to 104 weeks total drug exposure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Scio-469 30 Milligram (mg) | Experimental | Drug: SCIO-469SCIO-469 tablet will be administered orally at a dose of 30 mg thrice daily (90 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks. |
| Scio-469 60 mg | Experimental | Drug: SCIO-469SCIO-469 tablet will be administered orally at a dose of 60 mg thrice daily (180 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks. |
| Scio-469 90 mg | Experimental | Drug: SCIO-469SCIO-469 tablet will be administered orally at a dose of 90 mg thrice daily (270 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks. |
| Scio-469 120 mg | Experimental | Drug: SCIO-469SCIO-469 tablet will be administered orally at a dose of 120 mg thrice daily (360 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with a diagnosis of low/intermediate-1 MDS (for at least 12 weeks)
- Patients with anemia (average Hemoglobin < 10 g/dL or > or = to 4 units of Red Blood Cell counts in the last 8 weeks)
- Patients who have failed prior erythropoietin treatment
- Patients with an ECOG (Eastern Collaborative Oncology Group) score of 0, 1 or 2
Key exclusion criteria (6 listed)
- Patients with a International Prognostic Scoring System risk category high/intermediate-2
- Patients with treatment-related MDS associated with radiation, chemotherapy, and/or autologous transplant
- Patients with myelosclerosis (or myelofibrosis) occupying > 30 % marrow space
- Patients who have received decitabine (DacogenTM) for MDS
- Patients who have received lenalidomide (RevlimidTM), steroids, erythropoietin, hydroxyurea, or growth factors within 4 weeks before study drug administration
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SCIO-469SCIO-469 tablet will be administered orally at a dose of 30 mg thrice daily (90 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks. | Drug | Scio-469 30 Milligram (mg) |
| SCIO-469SCIO-469 tablet will be administered orally at a dose of 60 mg thrice daily (180 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks. | Drug | Scio-469 60 mg |
| SCIO-469SCIO-469 tablet will be administered orally at a dose of 90 mg thrice daily (270 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks. | Drug | Scio-469 90 mg |
| SCIO-469SCIO-469 tablet will be administered orally at a dose of 120 mg thrice daily (360 mg per day) for 16 weeks. Participants with hematologic improvement at Week 16 and as per Investigator's discretion on clinical benefit from treatment will continue the treatment for additional 36 weeks. | Drug | Scio-469 120 mg |
Primary outcome
Percentage of Participants With Major or Minor Erythroid Response (Hematological Improvement - Erythroid [HI-E])
Time frame: Week 16
Improvement in Erythroid (HI-E) lineage will be assessed as per International Working Group (IWG) criteria. HI-E major response is defined as greater than 2.0 gram per deciliter g/dL increase in hemoglobin for red blood cell (RBC) transfusion-dependent participants, transfusion independence. HI-E minor response is defined as 1.0 to 2.0 g/dL increase in hemoglobin for RBC transfusion-dependent participants and 50 percent decrease in transfusion requirements.
4 secondary outcomes
Percentage of Participants Achieving Major or Minor Neutrophil Response (HI-N)
Time frame: Week 16
Percentage of Participants Achieving Major or Minor Platelet Response (HI-P)
Time frame: Week 16
Percentage of Participants Achieving Complete or Partial Bone Marrow (BM) Response
Time frame: Week 16
Percentage of Participants Achieving Major or Minor Cytogenetic Response
Time frame: Week 16
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2013.
Related trials for Bone Marrow Diseases
RecruitingPhase 1/2
The Safety and Efficacy of Daratumumab in Patients With Refractory Aplastic Anemia
Aplastic Anemia, Refractory
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scios, Inc. Clinical Trial study director
Scios, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SCIO-469 in people with Bone Marrow Diseases and Myelodysplastic Syndromes, run by Scios, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Major or Minor Erythroid Response (Hematological Improvement - Erythroid [HI-E]) (time frame: Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2013.