Clinical trials

A clinical trial is a research study to answer specific questions about vaccines or new therapies or new ways of using known treatments.Clinical Trials also called medical research and research studies] are used to determine whether new drugs or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that work. Leads for clinical trials usually come from researchers. Once researchers test new therapies or procedures in the laboratory [animal studies] and get promising results, they begin planning Phase I clinical trials [in humans].New therapies are tested on people only after laboratory and animal studies show promising results. Clinical Trials make it possible to apply the latest scientific and technological advances to patient care.When a new medical treatment is studied for the first time in humans, it is not known exactly how it will work. With any new treatment, there are possible risks as well as benefits.

Clinical trials help physicians discover the answers to the following questions

1. Is the treatment safe and effective?

2. Is the treatment potentially better than the treatments currently available?

3. What are the side effects of the treatment?

4. Does the treatment have any possible risks?

5. How well does the treatment work?

Phases of a Clinical Trial

Clinical Trials are conducted in Phases, each designed to find out specific information. Each new phase of a clinical trial builds on information from previous stages.

Clinical Trials of experimental drugs proceed through Four phases.

Phase I. In Phase I clinical trials, researchers tests a new drug or treatment in a small group of people [20-80] for the first time to evaluate its

· Safety

· Determine a safe dosage range

· Identify side effects

Phase II. In Phase II clinical trial, the study drug or treatment is given to a larger group of people [100-300] to see if it is EFFECTIVE. And to further evaluate its Safety.

Phase III. In Phase III studies, the study drug or treatment is given to large groups of people [1000-3000] to confirm its

· Effectiveness

· Monitor side effects

· Compare it to commonly used treatments

· Collect information that will allow the drug or treatment to be used safely.

Phase IV. Phase IV studies are done after the drug or treatment has been marketed. These studies continue testing the study drug or treatment to collect information about their effect in various populations and any side effect associated with its long term use.

The clinical trial participants are willing volunteers. There are several advantages as well as potential side effects from participating in a clinical trial.

Types of Clinical Trials

Some clinical trials are Blinded, Placebo controlled. The blinding can be single, double or triple blinding.

Informed Consent

Prior to getting involved in a clinical trial, informed consent is to be obtained from the volunteers. Informed consent means that as a patient, he is given all the available information so that he can understand what is involved in a specific clinical trial.The researchers conducting the clinical trial will explain the treatment schedules, including its possible benefits and risks. The informed consent process is ongoing till the end of the trial.Every clinical trial is designed to meet a specific set of research criteria. Clinical trials are often expensive and time consuming. But, the results are often scientifically sound and rewarding.

Types of Stem Cell Transplants: Overview

There are many types of stem cell transplants. This section defines each of the various types of transplants.

First, stem cell transplants are defined by by the source of the stem cells.

• Bone marrow transplants are those that are obtained from the bone marrow. However, they are rarely performed today in myeloma because of the ability to collect stem cells from the peripheral blood (see below). Bone marrow transplants are sometimes used if insufficient numbers of stem cells can be obtained from the peripheral blood.
  
  
• Peripheral blood stem cell (PBSC) transplants are obtained from the peripheral blood. PBSC transplants are now performed much more often than bone marrow transplants because they are easier to collect, they provide a more reliable number of stem cells, the procedure puts less strain on the donor's system, and the patient recovers more quickly
  
  
• Cord blood transplants refer to transplants where the stem cells are obtained from umbilical cord blood. Historically they have not been used frequently due to limited numbers of stem cells that can be collected from each umbilical cord. Recently, however, exciting new data have been generated using multiple cord blood units from more than one donor.

Stem cell transplants are further categorized based on the donor who provides the stem cells.

• Autologous stem cell transplants (autografts) refer to stem cells that are collected from an individual and given back to that same individual. Most stem cell transplants in myeloma are autologous transplants.
  
  
• Allogeneic stem cell transplants (allografts) refer to stem cells that are taken from one person and given to another. Currently, these types of transplant are performed much less frequently in myeloma in the US and are usually performed in the context of clinical trials.
  
  
• Syngeneic stem cell transplants refer to stem cells that are taken from an identical twin of the recipient. These types of transplants are quite rare

Lastly, there are also several types of transplants under investigation in clinical trials.

• A tandem autologous transplant, also known as a double autologous transplant, requires the patient to undergo two autologous stem cell transplants within 6 months.
  
  
• A mini (nonmyeloablative) allogeneic transplant involves the use of moderately high-dose chemotherapy in combination with an allogeneic stem cell transplant.

Stem cell transplantation

Stem cell transplantation, performed as support for high-dose chemotherapy, is a treatment option for many patients with myeloma. Studies have shown that this treatment improves both the response rate and survival in myeloma over that obtained with conventional chemotherapy.

The Center for International Blood and Marrow Transplant Research (CIBMTR) estimates that approximately 4,700 stem cell transplants of various types were performed in patients with myeloma in North America in 2003 (CIBMTR, 2005).*

*The data presented here are preliminary and were obtained from the Statistical Center of the Center for International Blood and Marrow Transplant Research (CIBMTR). The analysis has not been reviewed or approved by the Advisory or Scientific Committee of the CIBMTR.

What It Is

A stem cell transplant is a procedure that is used in conjunction with high-dose chemotherapy, which is frequently more effective than conventional chemotherapy in destroying myeloma cells. Because high-dose chemotherapy also destroys normal blood-producing stem cells in the bone marrow, these cells must be replaced in order to restore blood cell production.

The first step in the process of stem cell transplantation is the collection of stem cells from a patient or a donor. When a patient's own stem cells are used, they are frozen and stored until needed. Stem cells can be collected from a donor when they are needed. The patient then receives high-dose chemotherapy and the stem cells are infused into the patient's bloodstream. The stem cells travel to the bone marrow and begin to produce new blood cells, replacing the normal cells lost during high-dose chemotherapy.

High-dose chemotherapy and stem cell transplantation are typically performed following several cycles of conventional chemotherapy (also known as induction therapy). Induction therapy is performed first in order to reduce the tumor burden.

Lineage

To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.^[21]

An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals dpp and adherins junctions that prevent germarium stem cells from differentiating^[22][23].

The signals that lead to reprogramming of cells to an embryonic-like state are also being investigated. These signal pathways include several transcription factors including the oncogene c-Myc. Initial studies indicate that transformation of mice cells with a combination of these anti-differentiation signals can reverse differentiation and may allow adult cells to become pluripotent.^[24] However, the need to transform these cells with an oncogene may prevent the use of this approach in therapy.

Stem Cells

Stem cells are primal cells found in all multi-cellular organisms. They retain the ability to renew themselves through mitotic cell division and can differentiate into a diverse range of specialized cell types. Research in the human stem cell field grew out of findings by Canadian scientists Ernest A. McCulloch and James E. Till in the 1960s.^[1][2]

The two broad categories of mammalian stem cells are: embryonic stem cells, derived from blastocysts and adult stem cells, which are found in adult tissues. In a developing embryo, stem cells can differentiate into all of the specialized embryonic tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing specialized cells.

As stem cells can be grown and transformed into specialized cells with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture, their use in medical therapies has been proposed. In particular, embryonic cell lines, autologous embryonic stem cells generated through therapeutic cloning, and highly plastic adult stem cells from the umbilical cord blood or bone marrow are touted as promising candidates.^[3]

Stem Cell Research

Stem cells are primal cells found in all multi-cellular organisms. They retain the ability to renew themselves through mitotic cell division and can differentiate into a diverse range of specialized cell types. Research in the human stem cell field grew out of findings by Canadian scientists Ernest A. McCulloch and James E.

The three broad categories of mammalian stem cells are: embryonic stem cells, derived from blastocysts, adult stem cells, which are found in adult tissues, and cord blood stem cells, which are found in the umbilical cord. In a developing embryo, stem cells can differentiate into all of the specialized embryonic tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing specialized cells.

As stem cells can be grown and transformed into specialized cells with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture their use in medical therapies has been proposed. In particular, embryonic cell lines, autologous embryonic stem cells generated through therapeutic cloning, and highly plastic adult stem cells from the umbilical cord blood or bone marrow are touted as promising candidates

Potency definitions

Pluripotent, embryonic stem cells originate as inner mass cells with in a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.

Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.

Totipotent stem cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent. These cells can differentiate into embryonic and extraembryonic cell types.

Pluripotent stem cells are the descendants of totipotent cells and can differentiate into cells derived from any of the three germ layers.

Multipotent stem cells can produce only cells of a closely related family of cells (e.g. hematopoietic stem cells differentiate into red blood cells, white blood cells, platelets, etc.).

Unipotent cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells.