Multiple MyelomaPhase 1/2NCT01183949
Effect of AT7519M Alone and AT7519M Plus Bortezomib in Patients With Previously Treated Multiple Myeloma
A Phase 1/2 study testing AT7519M and Bortezomib in people with Multiple Myeloma, run by Astex Pharmaceuticals, Inc. at 5 sites in United States.
Trial summary
The purpose of this study is to determine whether AT7519M alone or AT7519M plus bortezomib are effective treatments in patients with previously treated multiple myeloma. 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?
- AT7519M and Bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 5 sitesUnited States
- Study dates
- Nov 2010to Mar 2015
- Phase
- Phase 1/2
- 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
- Ability to understand the risks of the study and provide signed informed consent
- Age 18 years or older
- Relapsed and or Refractory MM
- Disease progression following at least two systemic treatments for MM
- Patient must be refractory to the last bortezomib
- ECOG performance status 0, 1 or 2
Who cannot join
- Pregnant or lactating females. Patients of childbearing potential must use appropriate birth control throughout the study
- Inadequate liver function
- Renal impairment
- Neutrophil count <1.0 x 10^9 /litre in the absence of growth factors
- Platelet count <50 x 10^9 /litre in patients in whom <50% of bone marrow nucleated cells are plasma cells and <30 x 10^9 /litre in patients in whom ≥50 % of bone marrow nucleated cells are plasma cells
- Hemoglobin <8g/dl in the absence of transfusion
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- Treated corrected calcium >ULN
- Serum creatine phosphokinase >ULN
- All previous cytotoxic therapies for MM must have been completed at least four weeks prior to treatment with AT7519M (two weeks for all non-cytotoxic therapy)
- Patients may be receiving concomitant therapy with biphosphonates and low dose corticosteroids. Bisphosphonates doses should be stable for at least 30 days prior to study drug administration. Corticosteroids doses should be stable for at least 7 days prior to study treatment
- Prior peripheral stem cell transplant within 12 weeks
- Evidence of mucosal or internal bleeding and/or platelet transfusion refractory (unable to maintain a platelet count >50 x 10^9 /litre)
- Ongoing infection requiring treatment
- Previous radiotherapy within 2 weeks of the start of the study
- Having previously received treatment with a cyclin-dependent kinase or GSK3beta inhibitor
- Incomplete recovery from previous radiotherapy other than residual cutaneous effects or stable < Grade 2 gastrointestinal toxicity
- Prior radiotherapy to the head and neck region for head and neck tumors
- Previous malignancy, except for non-melanomatous skin carcinomas, in situ carcinomas or malignancies with low risk of recurrence.
- Any severe or uncontrolled systemic conditions (e.g. systemic infection) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol
- Incomplete recovery from surgery other than stable < Grade 2 toxicity
- Peripheral neuropathy > Grade 2
- Abnormal left ventricular ejection fraction (< lower limit of normal for the institution for a patient of that age) on echocardiogram
- History of an ischemic cardiac event, including myocardial infarction within 3 months of study entry
- Congestive cardiac failure of ≥ grade 3 severity according to NYHA functional classification
- Unstable cardiac disease
- History or presence of bradycardia (≤60bpm), left bundle branch block, heart block, cardiac pacemaker or significant atrial tachyarrhythmias
- If the patient will receive bortezomib (Velcade) during part C of the study, concurrent treatment with any medication known strongly to inhibit or induce CYP3A4, CYP1A2 and CYP2C19 which cannot be discontinued at least two week prior to treatment with AT7519M (other than corticosteroids)
- Concurrent treatment with any medication that prolongs QT interval and may induce Torsades de Pointes and which cannot be discontinued at least two weeks prior to treatment with AT7519M
- Family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy
- Previous history of drug-induced QTc prolongation
- Screening 12-lead ECG with measurable QTc interval according to Fridericia's Correction of >450 msecs
- Screening 12-lead ECG with ST depression >1 mm in 2 or more leads or T wave inversion in 2 or more contiguous leads
- Prior history of infection with human immunodeficiency virus (HIV), known active hepatitis B or C viruses
- Diffuse infiltrative pulmonary or pericardial disease
- Known hypersensitivity to bortezomib, boron or any of the excipients of VelcadeTM
- Epilepsy or other convulsive disorder requiring active management
- Serious psychiatric illness, active alcoholism or drug addiction that may hinder or confuse follow up evaluation
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Massachusetts General Hospital
Boston, Massachusetts, MA02115
Dana Faber Cancer Institute
Boston, Massachusetts
MCW and Froedtert Clinical Cancer Center, Division of Neoplastic Diseases & Related Disorders
Milwaukee, Wisconsin, 53226
Memorial Sloan-Kettering Cancer Centre
New York, New York, 10065
About this study
Official title: A Phase I/II Open-label Multicenter Study of AT7519M Alone and in Combination With Bortezomib in Patients With Previously Treated Multiple Myeloma
The purpose of this study is to determine whether AT7519M alone or AT7519M plus bortezomib are effective treatments in patients with previously treated multiple myeloma.
Read the detailed description
The clinical study AT7519M/0004 is an open-label multicenter study to investigate the efficacy of AT7519M alone and AT7519M in combination with bortezomib in patients with previously treated multiple myeloma (MM).
- Conditions
- Multiple Myeloma
- Being tested
- AT7519M, Bortezomib
- Keywords
- Neoplasms, Neoplasms, Plasma Cell, Neoplasms by Histologic Type, Hemostatic Disorders, Paraproteinemias, Blood Protein Disorders, Hematologic Diseases, Hemorrhagic Disorders, Lymphoproliferative Disorders, Immunoproliferative Disorders, Immune System Diseases, Bortezomib, Antineoplastic Agents
- Medical subject headings
- Multiple Myeloma, Neoplasms, Neoplasms, Plasma Cell, Neoplasms by Histologic Type, Hemostatic Disorders, Paraproteinemias, Blood Protein Disorders, Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AT7519MDrug
Part A: Nine patients will receive AT7519M as an intravenous infusion on days 1, 4, 8 and 11 of a three week cycle. The starting dose of AT7519M will be 21mg/m^2/dose and will be increased to 27mg/m^2/dose during subsequent cycles in the absence of AT7519M-related toxicities.
Part B: Amendment clarified there will be no further exploration of AT7519M as a monotherapy.
Part C: Amendment modified dose escalation to a conventional 3 + 3 design with a maximum total of 14 patients will be treated at the maximum tolerated dose.
BortezomibDrug
Part C will treat between 3-26 patients with a combination of bortezomib and AT7519M in a dose escalation design. The starting doses for the dose escalation are bortezomib 1 mg/m2 and AT7519M 14 mg/m2.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Patients will be enrolled into 3 groups which will run sequentially. Groups A and B will receive AT7519M only, whereas Group C will receive AT7519M in combination with Bortezomib. Receives: Drug: AT7519M; Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the clinical efficacy of AT7519M alone or in combination with bortezomib
Efficacy will be assessed using the International Multiple Myeloma Working Group (IMWG) Response Criteria
Measured: Subjects with be followed until disease progression (an average of 4 cycles per subject. i.e an average of 84 days)
Secondary outcomes (3)
Assess the type, incidence and severity of clinically significant treatment emergent adverse events as assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) V 4.03
Measured: Subjects with be followed until disease progression (an average of 4 cycles per subject, i.e an average of approximately 84 days)
To define the pharmacokinetic profile of AT7519M and bortezomib when administered alone or in combination with bortezomib
The pharmacokinetic evaluation will include the calculation of plasma clearance and elimination phase half-life for AT7519M and bortezomib
Measured: 2 cycles (i.e an average of 42 days)
To identify the maximum tolerated dose (MTD) of AT7519M in combination with bortezomib
The MTD will be based on the incidence of dose limiting toxicities
Measured: Subjects with be followed until disease progression (an average of 4 cycles per subject, i.e an average of approximately 84 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2010 (estimated)
- Study startNov 2010
- Primary completionDec 2014
- Study completionMar 2015
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astex Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Multiple Myeloma Research Consortium
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01183949
- Sponsor's protocol ID
- AT7519M/0004
- Status last verified
- Aug 2024
- First submitted
- 17 Aug 2010
- Last updated
- 2 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Open-label Multicenter Study of AT7519M Alone and in Combination With Bortezomib in Patients With Previously Treated Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01183949
- Acronym / sponsor ID
- AT7519M/0004
- Conditions
- Multiple Myeloma
- Keywords
- Neoplasms, Neoplasms, Plasma Cell, Neoplasms by Histologic Type, Hemostatic Disorders, Paraproteinemias, Blood Protein Disorders, Hematologic Diseases, Hemorrhagic Disorders
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Astex Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Multiple Myeloma Research Consortium
- Study start
- Nov 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 18 Aug 2010 (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 whether AT7519M alone or AT7519M plus bortezomib are effective treatments in patients with previously treated multiple myeloma.
Detailed description
The clinical study AT7519M/0004 is an open-label multicenter study to investigate the efficacy of AT7519M alone and AT7519M in combination with bortezomib in patients with previously treated multiple myeloma (MM).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: AT7519M, Drug: BortezomibPatients will be enrolled into 3 groups which will run sequentially. Groups A and B will receive AT7519M only, whereas Group C will receive AT7519M in combination with Bortezomib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Ability to understand the risks of the study and provide signed informed consent
- Age 18 years or older
- Relapsed and or Refractory MM
- Disease progression following at least two systemic treatments for MM
- Patient must be refractory to the last bortezomib
Key exclusion criteria (37 listed)
- Pregnant or lactating females. Patients of childbearing potential must use appropriate birth control throughout the study
- Inadequate liver function
- Renal impairment
- Neutrophil count <1.0 x 10^9 /litre in the absence of growth factors
- Platelet count <50 x 10^9 /litre in patients in whom <50% of bone marrow nucleated cells are plasma cells and <30 x 10^9 /litre in patients in whom ≥50 % of bone marrow nucleated cells are plasma cells
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 |
|---|---|---|
| AT7519MPart A: Nine patients will receive AT7519M as an intravenous infusion on days 1, 4, 8 and 11 of a three week cycle. The starting dose of AT7519M will be 21mg/m^2/dose and will be increased to 27mg/m^2/dose during subsequent cycles in the absence of AT7519M-related toxicities. Part B: Amendment clarified there will be no further exploration of AT7519M as a monotherapy. Part C: Amendment modified dose escalation to a conventional 3 + 3 design with a maximum total of 14 patients will be treated at the maximum tolerated dose. | Drug | Treatment |
| BortezomibPart C will treat between 3-26 patients with a combination of bortezomib and AT7519M in a dose escalation design. The starting doses for the dose escalation are bortezomib 1 mg/m2 and AT7519M 14 mg/m2. | Drug | Treatment |
Primary outcome
To evaluate the clinical efficacy of AT7519M alone or in combination with bortezomib
Time frame: Subjects with be followed until disease progression (an average of 4 cycles per subject. i.e an average of 84 days)
Efficacy will be assessed using the International Multiple Myeloma Working Group (IMWG) Response Criteria
3 secondary outcomes
Assess the type, incidence and severity of clinically significant treatment emergent adverse events as assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) V 4.03
Time frame: Subjects with be followed until disease progression (an average of 4 cycles per subject, i.e an average of approximately 84 days)
To define the pharmacokinetic profile of AT7519M and bortezomib when administered alone or in combination with bortezomib
Time frame: 2 cycles (i.e an average of 42 days)
To identify the maximum tolerated dose (MTD) of AT7519M in combination with bortezomib
Time frame: Subjects with be followed until disease progression (an average of 4 cycles per subject, i.e an average of approximately 84 days)
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 2 Aug 2024.
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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.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AT7519M and Bortezomib in people with Multiple Myeloma, run by Astex Pharmaceuticals, Inc. at 5 sites in United States.
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 6 inclusion and 37 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 2 Aug 2024. 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 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?
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?
To evaluate the clinical efficacy of AT7519M alone or in combination with bortezomib (time frame: Subjects with be followed until disease progression (an average of 4 cycles per subject. i.e an average of 84 days)). 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 2 Aug 2024.