Status and phase
Conditions
Treatments
About
This phase II clinical trial design with a safety run-in period will be used to assess the rate of VGPR or better for the combination PVD-Dara in the treatment of RRMM.
Full description
A phase II clinical trial design, including an initial safety run-In period, will be used to assess the rate of VGPR or better for the combination PVD-Dara in the treatment of relapsed or refractory multiple myeloma.
In the run-in period, a maximum of 12 patients will be enrolled onto the trial using the initially proposed regimen and then the trial will be temporarily closed to enrollment, until safety data is reviewed for these patients. Adverse events during the first cycle of treatment of the initially proposed regimen will be closely monitored. If the safety criteria have been met as defined in the protocol, then the trial will reopen to enrollment using the regimen as planned until a total of 72 patients have been enrolled. If safety criteria have not been met as per protocol, then the treatment regimen will be modified for the second cohort of 12 patients after discussion with the study team taking into consideration that if intolerability is due to neutropenia the regimen will be modified by lowering the dose of pomalidomide.
The phase II will begin once the safe doses have been determined in the Run-in period. this Phase II clinical trial was designed to assess whether this 4-agent combination yields a response rate of VGPR or better in more than 65% of patients.
For the regimen found tolerable in the safety period, a two-stage Phase II clinical trial design was chosen to assess whether the VGPR or better response rate is at most 50% against the alternative that the VGPR or better response rate is at least 65%.
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Key Inclusion Criteria:
Histologically confirmed diagnosis of symptomatic multiple myeloma.
Evidence of disease progression or refractoriness to 1 to 3 prior lines of therapy by IMWG standard criteria.
Prior exposure to lenalidomide and a proteasome inhibitor is mandatory.
Daratumumab naïve patients or Daratumumab exposed patients who are not refractory to weekly or bi-weekly daratumumab.
Measurable disease:
ECOG Status 0-2 ≤ 14 days prior to registration
Adequate organ function including ≤ 14 days prior to registration defined as:
Adequate cardiac function within 8 weeks prior to registration defined as LVEF ≥ 40%.
Key Exclusion Criteria:
Disease refractory to weekly or bi-weekly daratumumab therapy.
Female patients who are lactating or have a positive serum pregnancy test ≤ 14 days from registration during the screening period.
Failure to have fully recovered from the reversible effects of prior anti-cancer therapy.
Major surgery within 14 days before registration.
Focal radiation therapy within 14 days prior to randomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma.
Disease-related central nervous system involvement.
Plasma cell leukemia, AL amyloidosis, or POEMS syndrome.
The subject has uncontrolled significant intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled congestive heart failure, New York Heart Association Class III-IV, unstable angina pectoris, stroke, myocardial infarction, uncontrolled cardiac arrhythmias < 6 months prior to registration, or uncontrolled hypertension.
Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
Known GI disease or GI procedure that could interfere with the oral absorption of study medication including difficulty swallowing.
Concurrent malignancy except for treated non-melanoma skin cancer, cervical carcinoma in situ and low-risk prostate CA being monitored without treatment.
Grade 2 and higher peripheral neuropathy on clinical examination ≤ 14 days prior to registration.
Chemotherapy ≤ 14 days prior to registration.
Exposure to an investigational drug (including investigational vaccine) or invasive investigational medical device for any indication within 4 weeks or 5 pharmacokinetic half-lives, whichever is longer.
Patients with known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal; moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note.
Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate.
Patients who have a contraindication to the use of any form of anticoagulation or antiplatelet agents.
Patient who are on a strong CYP34A or CYP1A2 inducer or inhibitors
Patients with Hepatic Child-Pugh score B and C. Note that Hepatic Child-Pugh score A are excluded from the Run-in-Period of the trial
Patient is:
Primary purpose
Allocation
Interventional model
Masking
0 participants in 1 patient group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal