Multiple MyelomaPhase 1NCT01764880
SST0001 (Roneparstat) in Advanced Multiple Myeloma
A Phase 1 study testing SST0001 (Roneparstat) in people with Multiple Myeloma, run by Sigma Tau Research Switzerland SA at 5 sites in 3 countries.
Trial summary
Heparanase cleaves heparan sulfate (HS) chains, a natural substrate for heparanase, and participates in degradation and remodelling of the extra-cellular matrix (ECM) facilitating, among other activities, cell invasion associated with cancer metastasis, angiogenesis, and inflammation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- SST0001 (Roneparstat)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 5 sitesin 3 countries
- Study dates
- Nov 2012to Nov 2016
- Phase
- Phase 1
- 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
- Advanced, heavily pretreated refractory multiple myeloma (MM).
- Patient should have exhausted all available anti MM therapies.
- Age ≥18 years.
- ECOG (Eastern Cooperative Oncology Group)performance status ≤ 2.
- Life expectancy of more than 3 months.
- No concomitant use of anticoagulants or antiplatelets drugs such as aspirin, NSAIDs (Nonsteroidal Antiinflammatory Drug), Clopidogrel, Unfractionated Heparin, Low Molecular Weight Heparin (e.g. Enoxaparin), Fondaparinux, Dabigatran, Rivaroxaban, Apixaban and Warfarin.
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- No platelets diseases or allergy to anticoagulants.
- WBC (White Blood Cell) ≥2000/µL; Platelets ≥50,000/µL; Hb ≥ 8 g/dL.
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN); AST (aspartate aminotransferase)and ALT (alanine aminotransferase)≤ 3 x the ULN; serum creatinine ≤ 1.5 x the ULN (Upper Limit of Normal).
- aPTT, TT, INR, fibrinogen, D-dimer within ULN.
- Disease free of prior malignancies for ≥ 3 years.
- No acute gastrointestinal bleeding or any major bleeding (e.g CNS) in the past 2 years or any significant bleeding history.
- No known central nervous system involvement by myeloma.
- Capacity of understanding the nature of the trial and giving written informed consent.
- Unless a female patient is post-menopausal or surgically sterilized, must be willing to use an acceptable method of birth control (hormonal contraceptive, intrauterine device, barrier contraceptive with spermicide, or abstinence) for the duration of the study.
- Male patient must agree to use an acceptable method for contraception (barrier contraceptive or abstinence) for the duration of the study.
Who cannot join
- Pregnancy or lactation or unwillingness to use adequate method of birth control
- Ascertained or presumptive hypersensitivity to the active principle and/or formulations ingredients.
- Active uncontrolled viral, bacterial, or fungal infection or history of HIV, hepatitis B or C, or any infection requiring systemic antivirals or antimicrobials.
- Grade ≥ 2 toxicity due to previous anti-neoplastic therapy (except alopecia), and Grade ≥ 3 peripheral motor or sensory neuropathy, in the 2 weeks before treatment (CTCAE V4.0).
- Less than 2 weeks since most recent chemotherapy, or concurrent chemotherapy.
- Presence of cirrhosis or chronic hepatitis.
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- Diagnosis of amyloidosis or diagnosis of plasma cell leukaemia.
- Presence of serious cardiac (congestive heart failure, angina pectoris, myocardial infarction within one year prior to study entry, uncontrolled hypertension or arrhythmia), neurological or psychiatric disorder.
- Presence of uncontrolled intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study.
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
Italy3 sites
U.O. Ematologia con Trapianto, Dipartimento dell'Emergenza e dei Trapianti di Organi
Bari, 70124
USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII
Bergamo, 24127
S.C. Ematologia, ASO S. Croce e Carle - Cuneo
Cuneo, 12100
About this study
Official title: Phase I Dose Finding Study Assessing Safety and Tolerability of SST0001 in Advanced Multiple Myeloma.
Heparanase cleaves heparan sulfate (HS) chains, a natural substrate for heparanase, and participates in degradation and remodelling of the extra-cellular matrix (ECM) facilitating, among other activities, cell invasion associated with cancer metastasis, angiogenesis, and inflammation. The heparanase enzyme is a promising target for development of new anticancer drugs. HS and the structurally related heparin are present in most animal species. As an analogue of the natural substrate of heparanase HS, heparin is considered to be a potent inhibitor of heparanase. SST0001 is a polymer with a heparin-like structure. It is a reduced oxidized N-acetyl heparin, these modifications cause the reduction of anticoagulant activity and are strictly related to the anti-heparanase activity. In preclinical murine models SST0001 showed a significant anti myeloma effect in multiple myeloma mice xenograft models, with a significant reduction of subcutaneous growth of different multiple myeloma cell lines, when SST0001 was administered either alone or in combination with dexamethasone. The purpose of this study is to determine the safety and tolerability of escalating doses of SST0001 in the treatment of advanced refractory multiple myeloma.
Read the detailed description
Multicenter, open label, uncontrolled Phase I First In Man trial in advanced refractory multiple myeloma, to determine the Maximum Tolerated Dose (MTD) of SST0001 given subcutaneously (sc) once daily for 5 or 10 days, in a cycle of 28 days. A starting dose of 25 mg (flat dose) is given once daily for 5 days (from Day 1 to Day 5). In the subsequent cohort 25 mg are administered once daily for 10 days (from Day 1 to 5 and from Day 8 to 12). Dose escalation with SST0001 administered for 10 days is performed in subsequent cohorts, depending on toxicities observed.
Indirect pharmacokinetics based on Activated Partial Thromboplastin Time (aPTT) modifications in all patients (minimum of 3 patients in each cohort) during the first cycle of treatment and direct SST0001 concentrations measurements.
Pharmacodynamics in all patients during the first cycle of treatment, based on modifications of coagulation parameters.
During the study any hints of anti-tumor activity will also be evaluated based on use of surrogate parameters (monoclonal serum and urine protein modifications).
- Conditions
- Multiple Myeloma
- Being tested
- SST0001 (Roneparstat)
- Keywords
- Heparanase inhibitor, Multiple myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SST0001 (Roneparstat)Drug
SST0001 once daily for 5 or 10 days in a cycle of 28 days.
| Study group | Role | What they receive |
|---|---|---|
| SST0001 (Roneparstat) | Experimental | SST0001 once daily for 5 or 10 days in a cycle of 28 days. Starting dose 25 mg, to be escalated in subsequent cohorts.
Duration of treatment depending on toxicities observed or until documentation of disease progression or other discontinuation criteria are met. Receives: Drug: SST0001 (Roneparstat) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD).
Maximum tolerated dose (MTD) (based upon first cycle study drug related dose limiting toxicities [DLTs]) of SST0001 given subcutaneously over repeated administration during each treatment cycle. MTD definition: ≥ 2/6 patients with a DLT at the first cycle (28 days).
Measured: 28 days of first cycle of therapy.
Secondary outcomes (9)
Adverse events, physical examination and laboratory tests.
Number of patients with adverse events, number of patients with abnormalities at physical examination and laboratory tests (hematology and biochemistry) as a measure of safety and local tolerability of SST0001. Safety assessments and severity of adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) V4.0.
Measured: 28 days of each cycle of therapy.
Maximum plasma concentration (Cmax)
Blood pharmacokinetics of SST0001 using Activated Partial Thromboplastin Time (aPTT)as indirect measurement of SST0001 equivalent plasma concentrations.
Measured: 28 days of first cycle of therapy.
Time to achieve Cmax (Tmax)
Measured: 28 days of first cycle of therapy.
Area under the concentration curve from administration to the last observed concentration time (AUClast)
Measured: 28 days of first cycle of therapy.
Half-life (T1/2)
Measured: 28 days of first cycle of therapy.
aPTT (Activated Partial Thromboplastin Time)
Pharmacodynamics of SST0001 in terms of effects on coagulation profile (aPTT, seconds).
Measured: 28 days of first cycle of therapy.
TT (Thrombin Time)
Pharmacodynamics of SST0001 in terms of effects on coagulation profile (TT, seconds).
Measured: 28 days of first cycle of therapy.
INR (International Normalized Ratio)
Pharmacodynamics of SST0001 in terms of effects on coagulation profile (INR).
Measured: 28 days of first cycle of therapy.
Tumor response.
Antitumor activity through the use of surrogate parameters (monoclonal serum and urine protein modifications), by means of serum and urine protein electrophoresis, immunoelectrophoresis and immunofixation, Serum Free Light Chain (FLC) Ratio and/or 24-h Bence-Jones urine protein.
M-protein (g/dL), Bence-Jones protein (g/24h), kappa FLC (mg/dL) and lambda FLC (mg/dL) will be assessed at each cycle of therapy. Responses will be evaluated according to International Myeloma Working Group (IMWG) Guidelines.
Measured: 28 days of each cycle of therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2013 (estimated)
- Study startNov 2012
- Primary completionNov 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sigma Tau Research Switzerland SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alessandro Rambaldi, MD, Principal investigator, USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, ItalyArnon Nagler, MD, Principal investigator, Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, IsraelManik Chatterjee, MD, Principal investigator, Universitätsklinik Würzburg, Medizinische Klinik und Poliklinik II (ZIM), Würzburg, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01764880
- Sponsor's protocol ID
- SST0001-STRCH-CR-11-002
- Status last verified
- Oct 2017
- First submitted
- 7 Jan 2013
- Last updated
- 23 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Finding Study Assessing Safety and Tolerability of SST0001 in Advanced Multiple Myeloma.
- ClinicalTrials.gov ID
- NCT01764880
- Acronym / sponsor ID
- SST0001-STRCH-CR-11-002
- Conditions
- Multiple Myeloma
- Keywords
- Heparanase inhibitor, Multiple myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Sigma Tau Research Switzerland SAIndustry (pharma, biotech, devices)
- Study start
- Nov 2012
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 10 Jan 2013 (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.
Heparanase cleaves heparan sulfate (HS) chains, a natural substrate for heparanase, and participates in degradation and remodelling of the extra-cellular matrix (ECM) facilitating, among other activities, cell invasion associated with cancer metastasis, angiogenesis, and inflammation. The heparanase enzyme is a promising target for development of new anticancer drugs. HS and the structurally related heparin are present in most animal species. As an analogue of the natural substrate of heparanase HS, heparin is considered to be a potent inhibitor of heparanase. SST0001 is a polymer with a heparin-like structure. It is a reduced oxidized N-acetyl heparin, these modifications cause the reduction of anticoagulant activity and are strictly related to the anti-heparanase activity. In preclinical murine models SST0001 showed a significant anti myeloma effect in multiple myeloma mice xenograft models, with a significant reduction of subcutaneous growth of different multiple myeloma cell lines, when SST0001 was administered either alone or in combination with dexamethasone. The purpose of this study is to determine the safety and tolerability of escalating doses of SST0001 in the treatment of advanced refractory multiple myeloma.
Detailed description
Multicenter, open label, uncontrolled Phase I First In Man trial in advanced refractory multiple myeloma, to determine the Maximum Tolerated Dose (MTD) of SST0001 given subcutaneously (sc) once daily for 5 or 10 days, in a cycle of 28 days. A starting dose of 25 mg (flat dose) is given once daily for 5 days (from Day 1 to Day 5). In the subsequent cohort 25 mg are administered once daily for 10 days (from Day 1 to 5 and from Day 8 to 12). Dose escalation with SST0001 administered for 10 days is performed in subsequent cohorts, depending on toxicities observed.
Indirect pharmacokinetics based on Activated Partial Thromboplastin Time (aPTT) modifications in all patients (minimum of 3 patients in each cohort) during the first cycle of treatment and direct SST0001 concentrations measurements.
Pharmacodynamics in all patients during the first cycle of treatment, based on modifications of coagulation parameters.
During the study any hints of anti-tumor activity will also be evaluated based on use of surrogate parameters (monoclonal serum and urine protein modifications).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SST0001 (Roneparstat) | Experimental | Drug: SST0001 (Roneparstat)SST0001 once daily for 5 or 10 days in a cycle of 28 days. Starting dose 25 mg, to be escalated in subsequent cohorts. Duration of treatment depending on toxicities observed or until documentation of disease progression or other discontinuation criteria are met. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Advanced, heavily pretreated refractory multiple myeloma (MM).
- Patient should have exhausted all available anti MM therapies.
- Age ≥18 years.
- ECOG (Eastern Cooperative Oncology Group)performance status ≤ 2.
- Life expectancy of more than 3 months.
Key exclusion criteria (9 listed)
- Pregnancy or lactation or unwillingness to use adequate method of birth control
- Ascertained or presumptive hypersensitivity to the active principle and/or formulations ingredients.
- Active uncontrolled viral, bacterial, or fungal infection or history of HIV, hepatitis B or C, or any infection requiring systemic antivirals or antimicrobials.
- Grade ≥ 2 toxicity due to previous anti-neoplastic therapy (except alopecia), and Grade ≥ 3 peripheral motor or sensory neuropathy, in the 2 weeks before treatment (CTCAE V4.0).
- Less than 2 weeks since most recent chemotherapy, or concurrent chemotherapy.
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 |
|---|---|---|
| SST0001 (Roneparstat)SST0001 once daily for 5 or 10 days in a cycle of 28 days. | Drug | SST0001 (Roneparstat) |
Primary outcome
Maximum tolerated dose (MTD).
Time frame: 28 days of first cycle of therapy.
Maximum tolerated dose (MTD) (based upon first cycle study drug related dose limiting toxicities [DLTs]) of SST0001 given subcutaneously over repeated administration during each treatment cycle. MTD definition: ≥ 2/6 patients with a DLT at the first cycle (28 days).
9 secondary outcomes
Adverse events, physical examination and laboratory tests.
Time frame: 28 days of each cycle of therapy.
Maximum plasma concentration (Cmax)
Time frame: 28 days of first cycle of therapy.
Time to achieve Cmax (Tmax)
Time frame: 28 days of first cycle of therapy.
Area under the concentration curve from administration to the last observed concentration time (AUClast)
Time frame: 28 days of first cycle of therapy.
Half-life (T1/2)
Time frame: 28 days of first cycle of therapy.
aPTT (Activated Partial Thromboplastin Time)
Time frame: 28 days of first cycle of therapy.
TT (Thrombin Time)
Time frame: 28 days of first cycle of therapy.
INR (International Normalized Ratio)
Time frame: 28 days of first cycle of therapy.
Tumor response.
Time frame: 28 days of each cycle of therapy.
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 23 Oct 2017.
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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.
Alessandro Rambaldi, MD principal investigator
USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
Arnon Nagler, MD principal investigator
Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel
Manik Chatterjee, MD principal investigator
Universitätsklinik Würzburg, Medizinische Klinik und Poliklinik II (ZIM), Würzburg, Germany
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SST0001 (Roneparstat) in people with Multiple Myeloma, run by Sigma Tau Research Switzerland SA at 5 sites in 3 countries.
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 16 inclusion and 9 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 23 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Italy, Germany, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Maximum tolerated dose (MTD). (time frame: 28 days of first cycle of therapy.). 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 23 Oct 2017; AzTrials last refreshed its copy on 30 Oct 2026.