- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02468687
NMP in Relapsed / Refractory Myeloma
A Phase I, Open Label Dose Escalation Trial of Orally Administered N-methyl-pyrrolidone (NMP) in Patients With Relapsed or Refractory Myeloma
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Victoria
-
Melbourne, Victoria, Australia, 3002
- Peter MacCallum Cancer Centre
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically confirmed diagnosis of plasma cell myeloma defined by WHO 2008 criteria
Measurable disease as defined by at least one of:
- serum M protein ≥5g/L
- urine M protein ≥ 200mg/24hrs
- involved serum free light chain ≥ 100mg/L
- measurable (by imaging at the discretion of the investigator) soft tissue plasmacytoma
- Relapsed, refractory or intolerant of both bortezomib and lenalidomide
Definitions:
- refractory at least 4 weeks of therapy administered, with less than a partial response by IMWG criteria
- relapsed from previous response (PR or greater) to therapy, with subsequent disease progression as defined as development of bone marrow dysfunction (fall in Hb of 20g/L or platelet count <100 x 109/L) due to increased bone marrow plasmacytosis
- OR new lytic bone lesions
- OR increase in serum M protein of 5g/L
- OR absolute increase of involved serum free light chain of >250mg/L
intolerant: grade 2 or higher toxicity unresponsive to dose adjustment 4. Prior autologous stem cell transplant, unless ineligible for transplant by the discretion of the investigator.
5. age ≥18 years 6. ECOG performance status <2 7. The following values within 7 days of commencing NMP (blood transfusions prior to study entry are permitted)
- Haemoglobin >80g/L
- Absolute neutrophil count >1.0 x 109/L
- Platelet count ≥ 25 x 109/L
- Creatinine clearance >30ml/min (by Cockcroft/Gault)
- Bilirubin ≤ 3x upper limit of normal (ULN)
- ALT ≤ 3 x ULN
- Left ventricular ejection fraction (LVEF) ≥45% (by gated cardiac blood pool scan or echocardiography) 9. Life expectancy > 3 months 10. Able to give written informed consent 11. In the opinion of the investigator, willing and able to comply with required study procedures 12. Able to take oral medications (no malabsorptive condition)
Exclusion Criteria:
- Pregnant or breastfeeding female patients
- Female of child bearing potential unwilling or unable to use two methods of contraception
- Received chemotherapy, immunotherapy or biological therapy within two weeks of enrolment. Prednisolone up to 20mg per day permitted for non-myeloma indications.
- Patients with a history of another malignancy within 2 years of the baseline visit, excluding treated non-melanotic skin cancer and in-situ carcinoma.
- Patients with known CNS involvement unless previously treated and well controlled for a period of ≥3 months AND which do not require the use of steroids.
Uncontrolled intercurrent illness including, but not limited to:
- Active or uncontrolled infection, including active HIV or viral (A, B or C) hepatitis. NOTE: Patients with controlled infection on antibiotic or antifungal therapy are eligible i.e. the patient should be afebrile for at least 72 hours and be haemodynamically stable.
Impaired cardiac function, including any of the following:
- Myocardial infarction within previous 3 months prior to starting study
- Symptomatic congestive heart failure (New York Heart Association Class III, IV)
- Symptomatic coronary artery disease
- Cardiac arrhythmia not controlled by medication
- Clinically significant resting bradycardia (<50 beats per minute)
- Long QT syndrome or a known family history of long QT syndrome or QTc > 450 msec on baseline ECG (using the QTcF formula). If QTcF >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
- Inability to monitor the QT/QTc interval on ECG
- Other clinically significant uncontrolled heart disease (e.g. unstable angina or uncontrolled hypertension)
- Impaired hepatic or renal impairment (see inclusion criteria)
- Uncontrolled diarrhoea, nausea or vomiting
- concomitant exposure to another investigational agent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: N-methyl-pyrrolidone
NMP dose escalation in accelerated phase and standard phase
|
NMP will be taken each morning as a single daily dose of oral suspension at a concentration of 50mg/ml on an empty stomach at least 30 minutes prior to food.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse events to establish the Maximum Tolerated Dose (MTD)
Time Frame: 28 days
|
Each patient will be monitored for adverse events during the first cycle of NMP treatment (28 days) to establish the maximum tolerated dose
|
28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Optimum biological dose (OBD)
Time Frame: 6 months
|
The maximum changes in correlative biomarkers will be tested at the specific time-points.
Descriptive statistics will be used to analyse data from correlative studies and summarized in graphical or tabular formats as appropriate.
|
6 months
|
Safety of the repeated dosing of NMP by oral administration - possible toxicities
Time Frame: 6 months
|
To assess safety, the numbers and rates (with confidence intervals) of patients experiencing any haematological and non-haematological and specific grade 3+ adverse events experienced at each given dose level and schedule of NMP will be calculated, over the full treatment period and by cycle
|
6 months
|
Pharmacokinetic properties of NMP after oral administration
Time Frame: Predose,0.5,1,2,4,8, 24 hours post dose
|
Pick plasma concentrations (Cmax) of NMP
|
Predose,0.5,1,2,4,8, 24 hours post dose
|
Response rate measured using IMWG criteria
Time Frame: 6 months up to 2 years
|
Patients will be evaluated for response after every 28 day cycle for the first 6 cycles of treatment and thereafter every 2 months in follow up using the IMWG criteria for multiple myeloma.
|
6 months up to 2 years
|
Time to progression from start of treatment
Time Frame: up to 3.5 years
|
Patients will be assessed for disease progression weekly in Cycle 1, then monthly on D1 of each cycle during treatment for the first 6 months and then monthly until disease progression, next anti-cancer treatment or death.
Time to progression from start of treatment will be estimated using Kaplan Meier survival curves.
|
up to 3.5 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: David Ritchie, Prof, Melbourne Health
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
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
Other Study ID Numbers
- HREC/14/MH/159
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.
Clinical Trials on Multiple Myeloma
-
Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
-
National Cancer Institute (NCI)Active, not recruitingSmoldering Multiple Myeloma | Refractory Multiple Myeloma | DS Stage I Multiple Myeloma | DS Stage II Multiple Myeloma | DS Stage III Multiple MyelomaUnited States
-
Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
Clinical Trials on N-methyl-pyrrolidone
-
James M Noble, MD, MS, CPH, FAANNational Institute on Aging (NIA)Enrolling by invitation
-
The University of Texas Health Science Center,...RecruitingNeuropsychiatric SyndromesUnited States
-
Stanford UniversityActive, not recruitingThyroid Cancer | Anaplastic Thyroid Cancer | Undifferentiated Thyroid CancerUnited States
-
Photolitec LLCNational Cancer Institute (NCI); Roswell Park Cancer InstituteRecruitingGlioblastoma Multiforme of Brain | Glioma, SarcomatousUnited States
-
Constellation PharmaceuticalsCompleted
-
Washington University School of MedicineCompleted
-
China Medical University HospitalTaipei City HospitalCompletedObsessive Compulsive DisorderTaiwan
-
Constellation PharmaceuticalsCompletedAdvanced Solid TumorsUnited States
-
Instituto Mexicano del Seguro SocialCentenario Hospital Miguel HidalgoCompleted
-
Reata, a wholly owned subsidiary of BiogenCompleted