A Phase I/II Trial of Romidepsin (Depsipeptide) and Bortezomib in Patients With Relapsed Myeloma

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-11-30

Study Completion Date

2012-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of the first phase of the study is to determine whether, and at what dose, depsipeptide, bortezomib and dexamethasone can be safely administered to patients with Multiple Myeloma. The second phase of the study will establish whether depsipeptide, bortezomib and dexamethasone is effective in the treatment of patients with multiple myeloma. The study will also examine the role of maintenance therapy with depsipeptide.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Trial of Romidepsin and Bortezomib for Multiple Myeloma

NCT00765102

Multiple Myeloma

TERMINATED PHASE2

Bortezomib and Dexamethasone as Treatment and Maintenance for Multiple Myeloma Relapse

NCT00335348

Multiple Myeloma

COMPLETED PHASE2

Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

NCT00609167

Multiple Myeloma and Plasma Cell Neoplasm

COMPLETED PHASE2

Bortezomib, Dexamethasone, and Cyclophosphamide in Treating Older Patients With Multiple Myeloma

NCT02082405

Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma

WITHDRAWN PHASE2

Study of Bortezomib and Dexamethasone With or Without Cyclophosphamide in Patients With Relapsed or Not Controllable Multiple Myeloma

NCT00813150

Multiple Myeloma

COMPLETED PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Multiple Myeloma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

depsipeptide

Cohort 1. Dose escalation, IV, Weeklyx3 in a 4week cycle. Cohort 2A. 12mg/m2, IV, Weeklyx3 in a 4week cycle. Cohort 2B. 12mg/m2, IV, Weeklyx2 in a 3week cycle.

Intervention Type DRUG

bortezomib

Cohort 1 and 2A. 3.5mg/m2, IV, day 1, 4, 8, 11 in 28 day cycle. Cohort 2B. 3.5mg/m2, IV, day 1, 4, 8, 11 in 21 day cycle

Intervention Type DRUG

dexamethasone

20mg for 2 days with each dose of bortezomib

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Romidepsin Velcade

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. 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.
2. Patient previously treated with bortezomib will be included in the study, if the duration of response was \>6mths from the completion of therapy.
3. Patient's age is \> 18 yrs
4. Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
5. Patient has given voluntary written informed consent.
6. 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.
7. 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)
8. Patient has a Karnofsky performance status ≥80%.
9. Patient has a life-expectancy \>3 months.
10. 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

1. Prior severe allergic reactions to bortezomib (Velcade), romidepsin, boron or mannitol
2. Neuropathy \> Grade 3 or Neuropathy of Grade 2 with pain \> Grade 1 by NCI-CTCAE criteria (v3.0).
3. 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.
4. Pregnancy in female patients

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No