Trial purpose
Cancer treatment
Tumor type
Haematological
Age
18+
Clinical summary
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. Nâ€ÂMethylâ€Â2â€Âpyrrolidone (NMP) is a small molecule acetylâ€Âlysine mimetic compound with potent (low micromolar range) immunomodulatory and direct antiâ€Âmyeloma activity attributable to BETbromodomain inhibition at higher concentrations. NMP is nontoxic, stable and already in use as a solvent in biomedical applications. It has been the subject of numerous toxicity studies in humans and been demonstrated to have few adverse effects. The study is proposing an empiric starting dose of 50mg daily, 50% of that seen in healthy volunteers with no observable toxicity. Dose escalation will follow a rule based on accelerated trial design in order to minimise the number of patients treated at subâ€Âtherapeutic doses and minimise the length of the study. During the accelerated doseâ€Âescalation phase, one patient will be entered per cohort with a dose escalation increment of 100%, with up to 6 dose escalation and up to two dose deâ€Âescalation levels.The accelerated phase ends when one patient experiences DLT during the first cycle of treatment or when a total of two patients have experienced moderate toxicity during the first cycle of treatment regardless of the dose level; or the most recent patient has been treated at the highest dose level in the first cycle. If 1 patient experiences a DLT in the first cycle at any dose level, the cohort will be further expanded to a total of 6 patients treated at the same dose level. The maximum tolerated dose (MTD) in the study will be defined as the highest dose in which the incidence of DLT was less than 33%.
Conditions
This trial is treating people with Multiple Myeloma
Eligibility
Inclusion
- 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
- 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:
- concomitant exposure to another investigational agent
Inclusion
- You have had treatment, but your cancer has come back (relapsed or recurrent).
- You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
Exclusion
- You have been diagnosed with a prior or secondary type of cancer.
- You have certain types of non-cancer medical conditions.
- You have had certain treatments, surgical procedures or drugs.
- You are currently being treated on a clinical trial.
Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.
More information
Trial Identifiers
Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:
Trial sponsor
Peter MacCallum Cancer Centre
Scientific Title
A Phase I, Open Label Dose Escalation Trial of Orally Administered N-methyl-pyrrolidone (NMP) in Patients With Relapsed or Refractory Myeloma
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