Zn-DDC to Target Hypoxia-NFkappaB-CSCs Pathway in Multiple Myeloma

Study Overview
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Brief Summary
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The outlook for patients with haematological malignancies remains challenging. It has been shown in some early cancer studies that a particular drug called Zn-DDC otherwise known as Imuthiol is highly toxic to cancer stem cells. Imuthiol has been intravenously used in clinical trials with an excellent safety record. Recent novel therapy and immunotherapy in haematological malignancies have improved outcome and survival but come with an increasing cost burden. Imuthiol could be an ideal affordable drug to study on it's own as well as in combination with other drugs in myeloma and other haematological malignancies. This may lead to potential combination therapies which will be very effective as well as affordable in the future. There is the need to look to see if this drug, Imuthiol and along with complementary drugs lenalidomide (Revlimid) and pomalidomide (Pomalyst) can help in haematological malignancy treatment. In order to do this there is the need to see how the cancer cells respond to the drugs in the laboratory before being able to trial the drug (or combination of drugs) out for treatment. The success of this study may lead to quick translation of Imuthiol into haematological malignancy treatment.

Detailed Description
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Up to 60 myeloma bone marrow samples from Myeloma patients and 10 bone marrow samples from other haematological malignancy samples (Acute leukaemia's) at Diagnosis and Relapse will be tested. Patients attending haematology clinics at New Cross Hospital will be reviewed for eligibility of the study by the clinician and if they meet the recruitment criteria, they will be approached to participate at clinic. After informed consent, participants will be asked to donate an additional 2-3ml sample of bone marrow in a single aliquot for the purpose of this study whilst undergoing a bone marrow aspirate as part of their routine clinical care at diagnosis and relapse.The single aliquot will be sent to the University of Wolverhampton for analysis. Specific clincial data will be collected at the time of diagnosis and relapse: Diagnosis Date diagnosed Disease stage Relapse status Age Sex Previous treatments Date of marrow sample Marrow trephine Marrow liquid The clinical data set will remain at The Royal Wolverhampton NHS Trust whilst analysis of the samples takes place. Once the samples have been analysed, the clinical data will then be released to determine relapsed or refractory disease and correlation with the in vitro data.

Official Title
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Zn-DDC to Target Hypoxia-NFkappaB-CSCs Pathway and Improve the Treatment Outcomes of Haematological Malignancies - A Translation Bench Study

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Zn-DDC
* Drug: Lanalidomide with Zn-DDC
* Drug: Pomalidomide with Zn-DDC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with haematological malignancy - either myeloma or acute leukaemia Patients must be 18 years or over Patients must be willing and able to give informed consent Exclusion Criteria: Pregnant patients will not be entered

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Zn-DDC<br>samples to be exposed with Zn-DDC (Imuthiol) alone | Drug: Zn-DDC<br>* Zn-DDC added to myeloma samples for culturing<br>|
| Lenalidomide with Zn-DDC<br>samples to be exposed with Lenalidomide in combination with Zn-DDC | Drug: Lanalidomide with Zn-DDC<br>* Lanalidomide with Zn-DDC added to myeloma samples for culturing<br>|
| Pomalidomide with Zn-DDC<br>samples to be exposed with Pomalidomide in combination with Zn-DDC | Drug: Pomalidomide with Zn-DDC<br>* Lanalidomide with Zn-DDC added to myeloma samples for culturing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Imuthiol and zinc efficacy | examine the cyctotoxicity of Imuthiol and zinc in combination with other drugs | 7 days | 
| Cell kill and determination of IC50 (inhibitory concentration) and apoptotic pathways involved | Cell kill and determination of IC50 (inhibitory concentration) and apoptotic pathways involved | 7 days |