Myeloma IX - Intensive Pathway

How is this trial run?

This trial is known as a randomised control trial. A randomised control trial is a trial in which patients with similar disease traits are selected by a computer to be placed in different groups that are comparing different treatments. There is no way at the time for your doctor or nurse to know which of the treatments is best and neither you nor your doctor get to choose which treatment you have. The choice of treatments will be made by a computer. The computer has no information about you as an individual.

Introduction

This trial looks at four things in three phases;

Phase One: Induction Phase
This phase compares two combinations of chemotherapy, and two types of bisphosphonate treatment.

Phase Two: Consolidation Phase
During this phase you will have a stem cell transplant regardless of which drugs you received in the induction phase.

Phase Three: Maintenance Phase
This phase compares receiving a drug called thalidomide after your main treatment is over with the standard treatment of no further drugs.

Induction Phase

Firstly, the trial aims to compare two standard induction chemotherapy treatments called CVAD and CTD and two bisphosphonate drugs called Clodronate which is given as a tablet and Zoledronic acid which is given through a drip into your vein. Bisphosphonate drugs can really help with some of the symptoms of your myeloma.

The drugs which make up CVAD are:

The CVA chemotherapies are given through a central line into your vein. The dexamethasone is given as a tablet. You will need to be in hospital for about 3 nights and take your tablets at home. To complete a course of CVAD will take about two weeks. Each full course is called a cycle and is repeated every three weeks, usually for four to six cycles.

The drugs which make up CTD are:

All of the CTD drugs are given as tablets. To complete a course of CTD will take about two weeks. Each full course is called a cycle and is repeated every three weeks, usually for four to six cycles.

So there are four combinations of drugs that you could be possibility be allocated to receive:

A: Clodronate & CVAD

B: Zoledronic Acid & CVAD

C: Clodronate & CTD

D: Zoledronic Acid & CTD

Your doctors expect your disease to respond well to any of the four combinations of drugs. However, if by the third cycle of treatment your disease is not responding as well as expected your doctor may replace your chemotherapy with an alternative treatment called Velcade (or bortezomib) and dexamethasone.

All of these treatments are followed by an autologous stem cell transplant using your own stem cells. *

Consolidation Phase: The Stem Cell Transplant

Between the 4th and 6th cycle of chemotherapy you will be given a higher dose of cyclophosphamide than you have had before and a ten day course of a drug called G-CSF. G-CSF is given as an injection under your skin and your nurse can teach you how to do this yourself or arrange for a district nurse to give the injection. G-CSF works by increasing the number of stem cells in your blood. Your stem cells will then be collected by filtering your blood through a special machine. The stem cells can then be cooled and stored ready for use when you need them.

After you have recovered from this part of the treatment you will go onto the high dose chemotherapy and stem cell transplant. During this phase you will receive a single dose of a chemotherapy known as Melphalan. This drug is given at a higher dose than your previous chemotherapy combinations.

After the Melphalan you will be given back your stem cells through an infusion into your central line. This is painless and will look and feel like having a blood transfusion. In total the high dose chemotherapy and stem cell transplant phase should keep you in hospital for about a month.

* If you are in general good health, have a brother or sister whose stem cells match yours and if they are willing to donate these to you as part of an allogeneic stem cell transplant then your doctor will discuss an allogeneic transplant as an alternative to receiving your own stem cells back. This part of the trial then compares using a lower dose of chemotherapy to prepare you for the allogeneic stem cell transplant with the standard high dose chemotherapy. However, if you have a transplant from a sister or brother you are then unable to enter the maintenance phase of this trial.

The Maintenance Phase

About six weeks after your autologous stem cell transplant you will be randomised to a group for the third part of the trial known as the maintenance phase.

Regardless of which group you were in for either your chemotherapy or your bisphosphonate treatment you will be randomly allocated to one of the two different groups in this phase.

If you are in the first group you will not receive any further treatment but will be carefully monitored by the doctor. Your doctor will physically examine you regularly and make a point of closely observing your condition.

If you are in the second group will be given a drug called thalidomide. The doses of thalidomide will start about six to ten weeks after your stem cell transplant and continue until you and your doctor decide otherwise. Thalidomide is taken as a tablet.

What might stop me from entering this trial?

You won't be asked to enter this trial for the following reasons:

• You are not experiencing any symptoms from your myeloma
• You have a solitary myeloma lesion in either your bone or soft tissue but no other signs of disease
• You have had previous treatment for your myeloma apart from local radiotherapy, bisphosphonate treatment or low doses of steroids
• If you have a serious medical condition
• If you are pregnant
• If you have had cancer in the last 5 years, apart from surgically removed non-melanoma skin cancer or other in situ carcinomas

What might being entered in this trial mean to me?

Tests and hospital visits

Before you enter the trial you will have a number of tests. This will tell your health care team about your general health and whether you are eligible for the trial or not.

The investigations may include:

This trial will mean some overnight hospital stays for you. The number of nights depends on the phase of the trial you are in.

In the induction phase you will have to stay overnight in hospital for three nights in order to have four days of chemotherapy. This will happen during every cycle.

In the consolidation phase you may have to stay in hospital for about a month in order to receive your high dose chemotherapy, the stem cell transplant and to give you lots of recovery time.

You will see your doctor and have a number of tests three months after the transplant.

In the maintenance phase you will come to the hospital as an outpatient every four weeks at first but this will gradually reduce to three monthly. This will be organized by your doctor or nurse.