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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02468687




Registration number
NCT02468687
Ethics application status
Date submitted
2/06/2015
Date registered
11/06/2015
Date last updated
15/02/2016

Titles & IDs
Public title
NMP in Relapsed / Refractory Myeloma
Scientific title
A Phase I, Open Label Dose Escalation Trial of Orally Administered N-methyl-pyrrolidone (NMP) in Patients With Relapsed or Refractory Myeloma
Secondary ID [1] 0 0
HREC/14/MH/159
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - N-methyl-pyrrolidone

Other: N-methyl-pyrrolidone - NMP dose escalation in accelerated phase and standard phase


Treatment: Drugs: N-methyl-pyrrolidone
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse events to establish the Maximum Tolerated Dose (MTD) - Each patient will be monitored for adverse events during the first cycle of NMP treatment (28 days) to establish the maximum tolerated dose
Timepoint [1] 0 0
28 days
Secondary outcome [1] 0 0
Optimum biological dose (OBD) - 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.
Timepoint [1] 0 0
6 months
Secondary outcome [2] 0 0
Safety of the repeated dosing of NMP by oral administration - possible toxicities - 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
Timepoint [2] 0 0
6 months
Secondary outcome [3] 0 0
Pharmacokinetic properties of NMP after oral administration - Pick plasma concentrations (Cmax) of NMP
Timepoint [3] 0 0
Predose,0.5,1,2,4,8, 24 hours post dose
Secondary outcome [4] 0 0
Response rate measured using IMWG criteria - 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.
Timepoint [4] 0 0
6 months up to 2 years
Secondary outcome [5] 0 0
Time to progression from start of treatment - 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.
Timepoint [5] 0 0
up to 3.5 years

Eligibility
Key inclusion criteria
1. Histologically confirmed diagnosis of plasma cell myeloma defined by WHO 2008 criteria

2. 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

3. 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)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnant or breastfeeding female patients

2. Female of child bearing potential unwilling or unable to use two methods of
contraception

3. Received chemotherapy, immunotherapy or biological therapy within two weeks of
enrolment. Prednisolone up to 20mg per day permitted for non-myeloma indications.

4. Patients with a history of another malignancy within 2 years of the baseline visit,
excluding treated non-melanotic skin cancer and in-situ carcinoma.

5. 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.

6. 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

7. concomitant exposure to another investigational agent

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Melbourne Health
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The study will evaluate if the N-methyl-pyrrolidone (NMP) can be safely administered to
humans at doses, which induce measurable immunological and anti-tumour effects in patients
with myeloma who are resistant to or intolerant of lenalidomide and bortezomib.
Trial website
https://clinicaltrials.gov/show/NCT02468687
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Ritchie, Prof
Address 0 0
Melbourne Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02468687