- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00431990
A Phase I/II Trial of Romidepsin (Depsipeptide) and Bortezomib in Patients With Relapsed Myeloma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Several groups have explored the possible synergistic interactions between proteasome and HDAC inhibitors in malignant hematopoietic cells. Bortezomib and HDACIs synergistically induce apoptosis, mitochondrial injury (via BAX), ROS generation and oxidative injury in human leukemia and myeloma cells.
In view of this evidence, we are proposing a trial to examine the clinical effects of combined romidepsin and bortezomib in patients with relapsed/refractory MM. However, there are currently no data as to whether these drugs are safe to administer in combination or at what dose toxicity they may become unacceptable.
Trial Design Open label, single centre, single arm, phase I/II dose escalation trial of bortezomib-dexamethasone with the addition of romidepsin followed by maintenance therapy until disease progression.
Primary objective:
• To determine the maximum tolerated dose (MTD) of romidepsin administered with Bortezomib in patients with relapsed multiple myeloma by the assessment of adverse events and abnormal laboratory values.
Primary endpoint:
• Toxicity evaluation at each of four dose levels presented in the dose-escalation schedule
Secondary objective:
• To determine the efficacy of this combination at the MTD in terms of (i) overall response, (ii) time to progression and (iii) overall survival
Secondary endpoints:
- Overall response (OR), defined as the best response on treatment based on M Protein response criteria with CR documented to EMBT standard and in conjunction with soft tissue plasmacytomas response criteria and corrected serum calcium level.
- Time to progression (TTP), defined as the time from commencement of treatment to the date of first evidence of progressive disease.
- Overall survival (OS), defined as the time from commencement of treatment to the date of death from any cause
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Joanne Dean
- Phone Number: 1809 613 9656 1111
- Email: Joanne.Dean@petermac.org
Study Contact Backup
- Name: Sam Ruell
- Phone Number: 1698 613 9656 1111
- Email: Sam.Ruell@petermac.org
Study Locations
-
-
Victoria
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Melbourne, Victoria, Australia, 8006
- Recruiting
- Peter MacCallum Cancer Centre
-
Sub-Investigator:
- Alvin Milner
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patient was previously diagnosed with multiple myeloma based on standard criteria treated with at least one, but less than 4 lines of therapy, and currently requires further treatment because of relapse from CR or PD.
- Patient previously treated with bortezomib will be included in the study, if the duration of response was >6mths from the completion of therapy.
- Patient's age is > 18 yrs
- Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
- Patient has given voluntary written informed consent.
- Female patients of child-bearing potential and male patients with female partners of child-bearing potential, one of whom has not undergone surgical sterilisation must agree to use 2 simultaneous methods of contraception. For female patients, a negative pregnancy test is to be performed within 7 days prior to administration of study drugs.
Patient has measurable disease.
- serum monoclonal protein (SEP) > 5 g/L
- serum-free light chains (SFLC) > 100 mg/L
- urine-free light chains (UFLC) > 200 mg/24hr
- measurable soft tissue (not bone) plasmacytoma (STPC)
- Patient has a Karnofsky performance status ≥80%.
- Patient has a life-expectancy >3 months.
Patient has the following laboratory values within 14 days before study drug administration:
- Platelet count ≥50 × 109/L without transfusion support within 7 days
- Hemoglobin ≥75 g/L without transfusion support within 7 days
- Absolute neutrophil count (ANC) ≥0.75 × 109/L without the use of growth factors.
- Corrected serum calcium <14 mg/dL (3.5 mmol/L).
- Serum potassium ≥ 4.0 mmol/L and serum magnesium ≥ 0.85 mmol/L (electrolytes can be corrected with supplementation. See section 9.7).
- Aspartate transaminase (AST): ≤2.5 × the upper limit of normal (ULN).
- Alanine transaminase (ALT): ≤2.5 × the ULN.
- Total bilirubin: ≤1.5 × the ULN.
- Calculated or measured creatinine clearance: ≥20 mL/minute.
Exclusion Criteria:
- Prior severe allergic reactions to bortezomib (Velcade), romidepsin, boron or mannitol
- Neuropathy > Grade 3 or Neuropathy of Grade 2 with pain > Grade 1 by NCI-CTCAE criteria (v3.0).
Patients with the following cardiac risk factors will be excluded from the study (as per the previous NCI trials):
- Congenital long QT syndrome
- QTc interval > 480 milliseconds
- Patients who have had a myocardial infarction within 12 months of study entry.
- Patients who have active coronary artery disease, e.g. angina as defined by Canadian Class II-IV (Appendix 3).
- Patients with an ECG showing evidence of cardiac ischemia (ST depression of ≥ 2 mm).
- Patients with congestive heart failure that meets NYHA Class II to IV definitions (Appendix 4) and/or ejection fraction < 45% by MUGA scan or < 50% by echocardiogram and/or MRI.
- Patients with a history of sustained VT, VF, Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD).
- Patients with dilated, hypertrophic, or restrictive cardiomyopathy from prior treatment or other causes (in doubt, see ejection fraction criteria above).
- Patients with uncontrolled hypertension, i.e. SBP ≥ 160 mm Hg or DBP ≥ 95 mm Hg.
- Patients with cardiac arrhythmia requiring anti-arrhythmic medication other than beta blocker or calcium channel blocker. Patients in whom digitalis cannot be discontinued are excluded from study.
- Patients with Mobitz II second degree heart block, that do not have a pacemaker.
Note: Patients with other cardiac disease may be excluded at the discretion of the principal investigator following consultation with cardiologist.
- Pregnancy in female patients
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Toxicity
Time Frame: Until progression
|
Until progression
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall response
Time Frame: Until progression
|
Until progression
|
Time to progression
Time Frame: Until progression
|
Until progression
|
Overall survival
Time Frame: Until progression
|
Until progression
|
Collaborators and Investigators
Investigators
- Principal Investigator: Simon J Harrison, MBBS, PhD., Peter MacCallum Cancer Centre, Australia
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antibiotics, Antineoplastic
- Dexamethasone
- Bortezomib
- Romidepsin
Other Study ID Numbers
- 06/34
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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