Multiple MyelomaPhase 1/2NCT01672736
A Trial of ASP7487 (OSI-906) in Combination With Bortezomib for the Treatment of Relapsed Multiple Myeloma
A Phase 1/2 study testing ASP7487, Velcade, Dexamethasone in people with Multiple Myeloma, run by University Health Network, Toronto at 6 sites in 2 countries.
Trial summary
This is a multi-center, open-label, non-randomized study. Patients will receive ASP7487 (OSI-906) in combination with bortezomib and dexamethasone. Phase 1 involves dose escalation of the combination, whereas Phase 2 involves the expansion of ASP7487 (OSI-906) combined with bortezomib and dexamethasone at the MTD to… 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?
- ASP7487, Velcade, Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 6 sitesin 2 countries
- Study dates
- Sep 2012to 27 Dec 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Males or females, age 18 years or older.
- Relapsed or relapse/refractory MM with at least 1 prior line of therapy for phase 1 and 1 to 5 prior lines of therapy for phase 2.
- Patients with measurable disease defined as at least one of the following
- Serum M-protein ≥ 0.5 g/dl (≥ 5 g/l)
- Urine M-protein ≥ 200 mg/24 h
- Serum free light chains (FLC) assay: Involved FLC level ≥ 10 mg/dl (≥ 100 mg/l) and an abnormal serum free light chain ratio (< 0.26 or > 1.65)
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- Biopsy proven plasmacytoma. Prior biopsy is acceptable.
- If the serum protein electrophoresis is unreliable for routine M-protein measurement, quantitative immunoglobulin levels on nephrolometry or turbidometry will be followed.
- ECOG ≤ 2 OR Karnofsky ≥ 60%.
- Predose mean QTc≤ 450 msec or QTcF ≤ 450 msec.
- Negative pregnancy test for Females of childbearing potential.
- Voluntary, written informed consent.
- Ability to understand the purpose and risks of the study.
- Must be able to take and retain oral medications.
- Inclusion Clinical Laboratories Criteria
- Absolute neutrophil count (ANC) > 1,000 cells/dL (1.0 x 109/L)
- Platelet count > 50,000 cells/dL (50 x 109/L)
- Hemoglobin ≥ 8.0 g/dL (4.96 mmol/L)
- Serum AST or ALT ≤ 1.2 x ULN
- Total bilirubin within normal limits
- Creatinine clearance ≥ 30 mL/min
- Serum creatinine ≤ 1.5 x ULN
- Serum calcium (ionized or corrected for albumin) ≥ 2.0 mmol/L (8.0 mg/dL or 1.0 mmol/L ionized calcium) to ≤ 1.2 x ULN.
- Serum potassium, and magnesium within normal limits
- HgbA1c of ≤ 7%
- Troponin I or T within normal limits
- BNP or NT-proBNP within normal limits
- Fasting glucose of ≤126 mg/dL (7.0 mmol/L).
- Resolution of prior treatment associated toxicities to ≤ grade 1
Who cannot join
- Bortezomib refractory patients are not permitted on the Phase 2 part of the study.
- Diagnosed or treated for another malignancy within 3 years of enrollment, except completely resected basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- Patient has received other investigational drugs or chemotherapy within 21 days or approved anti-myeloma therapy within 14 days.
- History (within the last 6 months) of significant cardiovascular disease.
- Mean QTcF interval > 450 msec at screening.
- Prior autologous, peripheral stem cell transplant within 12 weeks of the first dose of study drug.
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- Daily requirement for corticosteroids (except for inhalation corticosteroids).
- Patients with evidence of mucosal or internal bleeding and/or platelet transfusion refractory (i.e., unable to maintain a platelet count ≥ 50,000 cells/dL).
- Known active infection requiring parenteral or oral anti-infective treatment.
- Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation.
- Use of any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient.
- Patient has hypersensitivity to any of the components of study drugs.
- Known HIV or active hepatitis B or C viral infection.
- Diabetes mellitus currently requiring insulin or insulinotropic therapy or prior history of steroid induced diabetes.
- History of cerebrovascular accident (CVA) within 6 months prior to registration or that is not stable.
- Prior therapy with an IGF-1R inhibitor.
- Use of drugs that have a risk of causing QT interval prolongation and/or have a known risk of causing Torsades de Pointes (TdP) before 14 days or the recommended 5 half-life.
- Use of strong/moderate CYP1A2 inhibitors.
- Gastro-intestinal abnormalities that could affect the absorption of study drug.
- Peripheral neuropathy ≥ grade 2.
- Significant liver disease or metastatic disease to the liver
- History of amyloid, plasma cell leukemia or CNS involvement.
- Radiation therapy or major surgical procedure within 4 weeks of the first dose.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Canada4 sites
Queen Elizabeth II Health Sciences Center
Halifax, Nova Scotia, B3H2Y9
Hôpital Maisonneuve-Rosemont
Montreal, Quebec, H1T 2M4
Sir Mortimer B. Davis-Jewish General Hospital
Montreal, Quebec, H3T 1E3
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
United States2 sites
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
University Of Chicago Medical Center
Chicago, Illinois, 60637
About this study
Official title: A Phase 1/2 Trial of ASP7487 OSI-906)in Combination With Bortezomib and Dexamethasone for the Treatment of Relapsed or Relapsed/Refractory Multiple Myeloma
This is a multi-center, open-label, non-randomized study. Patients will receive ASP7487 (OSI-906) in combination with bortezomib and dexamethasone. Phase 1 involves dose escalation of the combination, whereas Phase 2 involves the expansion of ASP7487 (OSI-906) combined with bortezomib and dexamethasone at the MTD to establish the ORR. This trial will accrue patients with relapsed or relapsed/refractory MM - a disease state for which bortezomib is approved to treat by the FDA and Health Canada. The combination of ASP7487 (OSI-906) with bortezomib is supported by pre-clinical work in MM in which the combination with an IGF1-R inhibitor enhances anti-tumor activity of bortezomib.
Read the detailed description
The Phase 1 portion of the study will determine the MTD and DLTs of bortezomib administered on days 1, 4, 8 and 11 of a 21-day cycle combined with ASP7487 (OSI-906) dosed twice daily orally continuously. The combination of ASP7487 (OSI-906) with bortezomib has not previously been tested. The active agent bortezomib will be used during Cycle 1 - 8 at the recommended treatment dose of 1.3 mg/m2 days 1, 4, 8 and 11 and Cycles 9+ on days 1, 8, 15 and 22 of a 5-week cycle and ASP7487 (OSI-906) will be dose escalated form 75 mg to 150mg utilizing 3+3 design
- Conditions
- Multiple Myeloma
- Being tested
- ASP7487, Velcade, Dexamethasone
- Keywords
- Relapsed or relapse/refractory Multiple Myeloma
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASP7487, Velcade, DexamethasoneDrug
Also called ASP7487, Bortezomib, Dexamethasone
ASP7487- Oral (75, 100, 150 mg)BID Bortezomib- 1.3 mg/m2 IV on days 1, 4, 8, 15 of each 21 day cycle up to cycle 8 and days 1, 5, 15, 22 of each 35 day cycle beyond cycle 9 Dexamethasone- 20 mg on the day of Bortezomib administration
| Study group | Role | What they receive |
|---|---|---|
| ASP7487, Velcade, Dexamethasone | Experimental | ASP7487 administered orally 75, 100 and 150 mg) BID continuously for each cycle. Bortezomib administered at 1.3 mg/m2 twice weekly for the first 8 21 day cycles and once weekly beyond cycle 9 for 35 day cycles. Dexamethasone is administered on bortezomib administration days at 20 mg Receives: Drug: ASP7487, Velcade, Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose of the Combination of ASP7487 (OSI-906) With Velcade and Dexamethasone
- Phase 1: To determine the maximum tolerated dose (MTD) of ASP7487 (OSI-906) administered in combination with the recommended dose and schedule of bortezomib and dexamethasone;
- Phase 2: To evaluate the antitumor activity of ASP7487 (OSI-906) in combination with bortezomib and dexamethasone at the MTD established from the Phase 1 component.
Measured: 45 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2012 (estimated)
- Study startSep 2012
- Primary completion27 Mar 2017
- Study completion27 Dec 2017
Why it stopped: The Sponsor decided to stop further manufacture the study drug 'Linsitinib' in Nov 2015.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Multiple Myeloma Research Consortium, Astellas Pharma Inc
- Responsible party
- Sponsor
- Investigators
- Suzanne Trudel, MD, Principal investigator, UHN-PMH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01672736
- Sponsor's protocol ID
- PMHOSI906-MM001
- Status last verified
- Sep 2018
- First submitted
- 1 Aug 2012
- Last updated
- 13 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Trial of ASP7487 OSI-906)in Combination With Bortezomib and Dexamethasone for the Treatment of Relapsed or Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01672736
- Acronym / sponsor ID
- PMHOSI906-MM001
- Conditions
- Multiple Myeloma
- Keywords
- Relapsed or relapse/refractory Multiple Myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Sponsor decided to stop further manufacture the study drug 'Linsitinib' in Nov 2015.
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Multiple Myeloma Research Consortium, Astellas Pharma Inc
- Study start
- Sep 2012
- Primary completion
- 27 Mar 2017 (actual)
- Study completion
- 27 Dec 2017 (actual)
- First posted
- 27 Aug 2012 (estimated)
- Results
- Posted 13 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-center, open-label, non-randomized study. Patients will receive ASP7487 (OSI-906) in combination with bortezomib and dexamethasone. Phase 1 involves dose escalation of the combination, whereas Phase 2 involves the expansion of ASP7487 (OSI-906) combined with bortezomib and dexamethasone at the MTD to establish the ORR. This trial will accrue patients with relapsed or relapsed/refractory MM - a disease state for which bortezomib is approved to treat by the FDA and Health Canada. The combination of ASP7487 (OSI-906) with bortezomib is supported by pre-clinical work in MM in which the combination with an IGF1-R inhibitor enhances anti-tumor activity of bortezomib.
Detailed description
The Phase 1 portion of the study will determine the MTD and DLTs of bortezomib administered on days 1, 4, 8 and 11 of a 21-day cycle combined with ASP7487 (OSI-906) dosed twice daily orally continuously. The combination of ASP7487 (OSI-906) with bortezomib has not previously been tested. The active agent bortezomib will be used during Cycle 1 - 8 at the recommended treatment dose of 1.3 mg/m2 days 1, 4, 8 and 11 and Cycles 9+ on days 1, 8, 15 and 22 of a 5-week cycle and ASP7487 (OSI-906) will be dose escalated form 75 mg to 150mg utilizing 3+3 design
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ASP7487, Velcade, Dexamethasone | Experimental | Drug: ASP7487, Velcade, DexamethasoneASP7487 administered orally 75, 100 and 150 mg) BID continuously for each cycle. Bortezomib administered at 1.3 mg/m2 twice weekly for the first 8 21 day cycles and once weekly beyond cycle 9 for 35 day cycles. Dexamethasone is administered on bortezomib administration days at 20 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Males or females, age 18 years or older.
- Relapsed or relapse/refractory MM with at least 1 prior line of therapy for phase 1 and 1 to 5 prior lines of therapy for phase 2.
- Patients with measurable disease defined as at least one of the following
- ECOG ≤ 2 OR Karnofsky ≥ 60%.
- Predose mean QTc≤ 450 msec or QTcF ≤ 450 msec.
Key exclusion criteria (23 listed)
- Bortezomib refractory patients are not permitted on the Phase 2 part of the study.
- Diagnosed or treated for another malignancy within 3 years of enrollment, except completely resected basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- Patient has received other investigational drugs or chemotherapy within 21 days or approved anti-myeloma therapy within 14 days.
- History (within the last 6 months) of significant cardiovascular disease.
- Mean QTcF interval > 450 msec at screening.
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 |
|---|---|---|
| ASP7487, Velcade, DexamethasoneAlso: ASP7487, Bortezomib, DexamethasoneASP7487- Oral (75, 100, 150 mg)BID Bortezomib- 1.3 mg/m2 IV on days 1, 4, 8, 15 of each 21 day cycle up to cycle 8 and days 1, 5, 15, 22 of each 35 day cycle beyond cycle 9 Dexamethasone- 20 mg on the day of Bortezomib administration | Drug | ASP7487, Velcade, Dexamethasone |
Primary outcome
Maximum Tolerated Dose of the Combination of ASP7487 (OSI-906) With Velcade and Dexamethasone
Time frame: 45 months
* Phase 1: To determine the maximum tolerated dose (MTD) of ASP7487 (OSI-906) administered in combination with the recommended dose and schedule of bortezomib and dexamethasone; * Phase 2: To evaluate the antitumor activity of ASP7487 (OSI-906) in combination with bortezomib and dexamethasone at the MTD established from the Phase 1 component.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Suzanne Trudel, MD principal investigator
UHN-PMH
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ASP7487, Velcade, Dexamethasone in people with Multiple Myeloma, run by University Health Network, Toronto at 6 sites in 2 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 29 inclusion and 23 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: stopped early, as of the sponsor's last update on 13 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Canada, United States. 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 combined 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.
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?
Yes. Results are posted in the registry (first posted 13 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 of the Combination of ASP7487 (OSI-906) With Velcade and Dexamethasone (time frame: 45 months). 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 13 Sep 2018.