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Study on Fludarabine, Melphalan, and Radiation for Patients with High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia Preparing for Stem Cell Transplant.

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is focused on patients with High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia. These are serious blood disorders where the bone marrow does not produce enough healthy blood cells. The study aims to explore a treatment approach that combines chemotherapy and radiation therapy to prepare patients for a bone marrow transplant. The chemotherapy drugs used in this study include Fludarabine Phosphate and Melphalan, which are given to help destroy cancer cells and make room for new, healthy cells from a donor. The radiation therapy, known as Total Marrow and Lymphoid Irradiation (TMLI), targets the bone marrow and lymphoid tissues to further prepare the body for the transplant.

In addition to Fludarabine Phosphate and Melphalan, other medications such as Mycophenolate Mofetil, Cyclophosphamide, and Tacrolimus are used to support the treatment process. These medications help suppress the immune system to prevent it from attacking the new donor cells, a process known as immunosuppression. The study also involves a placebo group to compare the effects of the treatment. The main goal of the study is to assess the effectiveness of this treatment combination in improving the chances of survival without the disease getting worse over a period of two years.

The study will take place over several months, with patients receiving the treatment and then being monitored for their response. The treatment involves a series of infusions and oral medications, with the entire process carefully supervised by medical professionals. Patients will be regularly checked for any side effects or complications, and their progress will be closely followed to ensure the best possible outcomes. The study aims to provide valuable insights into how this combination of treatments can benefit patients with these high-risk blood disorders.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Initial assessment and preparation
Upon joining the study, an initial assessment is conducted to confirm eligibility. This includes a review of medical history and current health status.
A meeting is held to discuss the procedure, potential risks, and benefits. Informed consent is obtained.
Step 2
Conditioning regimen
The conditioning regimen begins with the administration of fludarabine phosphate and melphalan intravenously. This phase prepares the body for the transplant by reducing the immune response and creating space in the bone marrow.
The specific dosage and frequency are determined by the medical team based on individual health factors.
Step 3
Total marrow and lymphoid irradiation (TMLI)
Following the conditioning regimen, total marrow and lymphoid irradiation (TMLI) is administered. This process involves targeted radiation to further prepare the body for the transplant.
Step 4
Stem cell transplantation
The allogeneic hematopoietic stem cell transplantation (AHSCT) is performed. This involves the infusion of healthy stem cells from a donor to replace the damaged or diseased bone marrow.
Step 5
Post-transplant medication
After the transplant, medications such as tacrolimus and mycophenolate mofetil are administered to prevent rejection and manage the immune response. These are given intravenously and orally, respectively.
The dosage and duration are tailored to individual needs and monitored closely by the healthcare team.
Step 6
Monitoring and follow-up
Regular follow-up appointments are scheduled to monitor recovery and assess for any complications, such as infections or graft-versus-host disease (GVHD).
Measurable residual disease (MRD) is assessed at various intervals post-transplant to evaluate the effectiveness of the treatment.

Who can join the trial?

14 criteria

The participant must be able and willing to sign a document that shows they agree to join the study. If an adult has mild cognitive issues, a legally authorized representative can help.
The level of a substance called serum creatinine in the blood should be 1.3 mg/dL or less, or the kidneys should clear creatinine at a rate of 80 mL/min or more over 24 hours.
Women who can have children must have a negative pregnancy test, either through urine or blood.
Men and women who can have children must agree to use birth control methods, like hormonal or barrier methods, or choose not to have sex, before joining the study and for six months after the study ends. If a woman becomes pregnant or thinks she might be pregnant during the study, she should tell her doctor right away.
Tests to check lung function should show that the amount of air you can forcefully exhale in one second (FEV1) and the ability of the lungs to transfer carbon monoxide (DLCO) are at least 50% of what is expected for a healthy person.
A heart test called an electrocardiogram should show no signs of heart problems or irregular heartbeats, and the heart's ability to pump blood, known as the ejection fraction, should be 50% or more, as shown by a MUGA scan or echocardiogram.
The participant, a family member, and the transplant team (doctor, nurse, and social worker) must meet at least once before the transplant starts to discuss the risks and benefits, as well as other treatment options. The participant must sign a consent form.
The participant should be 50 years or older, or have a pre-transplant score of 3 or more on the HCT-CI scale, or have any condition that prevents the use of a strong conditioning treatment.
The participant should have a Karnofsky performance status of 70% or more, which measures their ability to perform daily activities.
The participant should have a condition called myelodysplastic syndrome or acute myeloid leukemia, or have leukemia that has returned or is not responding to treatment, or be in complete remission with some remaining disease as shown by specific tests.
The participant must have a donor who is a perfect match in 8 out of 8 HLA markers, or an unrelated donor with at least 8 out of 8 HLA matching. Some mismatches are allowed. Any blood type differences between donor and recipient can be managed with special techniques.
At least 14 days must have passed since the participant finished their last round of initial or repeated treatment.
The level of a substance called total bilirubin in the blood should be 1.5 times the upper limit of normal or less, or 3 times the upper limit for those with Gilbert's disease.
The levels of liver enzymes called SGOT and SGPT should be 5 times the upper limit of normal or less.

Who cannot join the trial?

4 criteria

Patients who have a different type of cancer than High-Risk Myelodisplastic Syndrome or Acute Myeloid Leukemia cannot participate. These are specific blood-related conditions.
Patients who are candidates for myeloablative conditions are excluded. This means they are able to undergo a very intense treatment that destroys bone marrow cells.
Patients who are not within the specified age range for the study cannot participate. The study has specific age requirements.
Patients who belong to a vulnerable population, which means they might need special protection or care, are not included in this study.

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Virgen del Rocío University Hospital
Sevilla, Spain

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Investigated drugs

Fludarabine
is a medication used in this trial to help prepare the body for a stem cell transplant. It works by weakening the immune system, which helps the new stem cells to grow and develop properly. This medication is part of a reduced-intensity regimen, meaning it is less harsh on the body compared to traditional treatments.
Melphalan
is another medication used in the trial as part of the conditioning process before a stem cell transplant. It helps to destroy any remaining cancer cells and makes space in the bone marrow for the new stem cells to grow. Like fludarabine, melphalan is used in a reduced-intensity regimen to minimize side effects.
Total Marrow and Lymphoid Irradiation (TMLI)
is a type of radiation therapy used in this trial. It targets the bone marrow and lymphoid tissues to eliminate cancer cells and suppress the immune system. This helps the new stem cells to engraft, or take hold, in the patient's body. TMLI is combined with the medications fludarabine and melphalan to improve the chances of a successful transplant.

What is already known about the treatment

Fludarabine
Fludarabine is administered intravenously and is used in combination with other medications for conditioning before allogeneic hematopoietic stem cell transplantation. It is currently being studied in clinical trials for its effectiveness in treating high-risk myelodysplastic syndrome and acute myeloid leukemia. The main therapeutic indication is to prepare the body for stem cell transplantation by suppressing the immune system. At the molecular level, fludarabine works by interfering with DNA synthesis, which inhibits the growth of cancer cells. It is classified as an antimetabolite in pharmacology.
Melphalan
Melphalan is given intravenously and is part of a conditioning regimen for patients undergoing stem cell transplantation. It is being evaluated in clinical trials for its role in treating high-risk myelodysplastic syndrome and acute myeloid leukemia. The primary therapeutic use is to help prepare patients for transplantation by reducing the number of cancer cells. Melphalan acts by cross-linking DNA strands, which prevents cancer cells from dividing and growing. It belongs to the class of alkylating agents in pharmacology.

Investigated diseases

High-Risk Myelodysplastic Syndrome
This condition is a group of disorders caused by poorly formed or dysfunctional blood cells. It occurs when something goes wrong in the bone marrow, where blood cells are produced. Patients with high-risk myelodysplastic syndrome have a higher chance of the disease progressing to acute myeloid leukemia. Symptoms may include fatigue, shortness of breath, and easy bruising or bleeding due to low blood cell counts. The disease can progress slowly or quickly, depending on the specific type and risk factors. Monitoring and regular check-ups are essential to manage the condition effectively.
Acute Myeloid Leukemia
This is a type of cancer that starts in the blood-forming cells of the bone marrow and quickly moves into the blood. It is characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. Symptoms often include fatigue, fever, frequent infections, and easy bruising or bleeding. The disease progresses rapidly and requires immediate medical attention. It is more common in older adults but can occur at any age. Regular monitoring and medical evaluations are crucial for managing the disease.