Patients & Families

The International Study for Treatment of Childhood Relapsed ALL (IntReALL) is the largest international clinical trial which seeks to discover the best treatment strategies and investigate innovative therapies for children with relapsed ALL.

The study has three aims:

• Investigating the effectiveness of a new drug (Inotuzumab) in relapsed ALL
• Investigating the effectiveness of 2 courses of Blinatumomab during late consolidation/maintenance therapy
• Confirming the effectiveness of 1 course of Blinatumomab replacing the 2^nd standard of care consolidation course in high risk patients

For more info on the clinical trial set-up: The Trial

All children who are diagnosed with relapsed ALL. The exact trial course will differ depending on the risk factor.

Please understand that the more children take part, the more information can be gathered to help us improve the treatment of children with relapsed ALL.

It means that if your child participates in the study, he/she will be randomly assigned to one of the proposed treatment arms. For example, In the standard risk group, this means your child will either follow the induction therapy protocol with the new drug Inotuzumab or the ALL R3 induction protocol. Following the induction phase, a second randomization will assign patients to the respective standard consolidation therapy either with or the tested drug Blinatumomab.

In other words, your child will be assigned to one of the following groups:

• Standard treatment ALL R3 induction and consolidation with Blinatumomab
• Standard treatment ALL R3 induction and consolidation without Blinatumomab
• Inotuzumab induction and consolidation with Blinatumomab
• Inotuzumab induction and consolidation without Blinatumomab

Each randomization is done by a computer. Half of the children who participate in the study are expected to receive the new drug Inotuzumab.

The IntReALL study has been designed by experts in the field based on the knowledge available up to date. The safety of patients in clinical trials is of utmost importance. All trial protocols have been reviewed and approved by ethics and regulatory committees.

Please note that the treatment arms may differ and are non-randomized for high risk and very high risk patients. Visit this page for more detailed information on the trial setup.

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Regardless of the group to which your child is assigned to, the treatment comprises the following 4 phases:

1^st Phase: Induction Therapy (5 weeks)

Intensive therapy will be given with the aim to eradicate all – or at least most – malignant cells at the beginning. We expect your child to remain in the hospital mots of the time during this phase. At the end of this course, we will check the bone marrow to assess if the disease is in remission.

2^nd Phase: Early Consolidation (8 weeks)

The second round of chemotherapy is meant to consolidate the anti-cancer effect of the induction phase. During this phase, we expect your child to be hospitalized only when receiving treatment, to deal with side-effects and possible complications, or to recover from treatment. At the end of this phase, the physicians will decide how to proceed with the treatment. If your child has not relapsed and has only a minimal residual disease (MRD), phase 3 treatment can be initiated.

3^rd Phase: Late Consolidation (12-15 weeks)

It is standard in ALL therapy that the consolidation treatment is repeated with the intention to eradicate all possibly still existing, but not visible cancer cells. If the MRD measures are high, which means that cancer cells are still detectable, your child will be referred to: Hematopoietic Stem Cell Transplantation (HSCT)

4^th Phase: Maintenance Therapy (90-100 weeks)

It has been proven that after intensive treatment, a longer period of less intensive treatment will improve the outcome in a considerably high number of ALL patients. As the medication in this phase will predominantly be given orally, your child will be able to tsay at home most of the time and will most likely be able to take part in regular activities (such as school, sports etc.)

The total duration of treatment for those patients receiving chemotherapy as late consolidation and maintenance might vary a bit due to the individual situation. If a hematopoietic stem cell transplantation should be necessary, the chemotherapy will end after the early consolidation phase.

If the disease progresses during the treatment or if side-effects are severe, your child's physician may decide to stop the therapy before completion. In this case, they will consult with other experts on the IntReALL study about other options or will propose palliative care. All this will be thoroughly discussed with you.

Regardless of the group your child is assigned to, it is important to keep in mind that most drugs used in the treatment of childhood cancer have similar side effects which consists of:

• Bone marrow suppression: This causes increased risk of infection, anaemia and bleeding. Your child may require transfusion support to treat anaemia and the low platelet count caused by the treatment. Doctors will advise on the precautions required to prevent infection and inform about how potential infections are treated.
  
  
• Nausea, loss of appetite, weight loss: We can use strong anti-emetic drugs to minimise nausea. We can provide help for children who are unable to eat enough.
  
  
• Hair loss: This is not permanent. Hair will grow back after treatment has finished or is otherwise stopped.

If your child experiences any other serious side-effects from the treatment, an alternative treatment plan will be proposed by your child's physician and you will be asked to consent to the new treatment plan. Please keep in mind that chemotherapy may have some long-term effects. As in standard treatment, there is a slight risk that fertility might be impaired and additional malignant diseases, so-called secondary malignancies, may arise. Your child's physician will advise on age-appropriate measures that can be taken to ensure fertility after end of treatment.

No. Children are very closely monitored whilst receiving treatment and, if not already hospitalized, they will need to attend their treatment centre at least weekly. This is the same for patients on this study as well as on standard ALL relapse treatment.

All bone marrow, blood and tissue samples will be collected when the routine tests (as in standard treatment) are done. Thus, no additional tests will be necessary.

We may wish to take an extra few millilitres of bone marrow when we do our routine testing. If your child is receiving Inotuzumab, at the time of routine blood count monitoring, small additional blood samples (5 mL) may be required to monitor the levels of Inotuzumab.

We would like to ask your permission to store some of these samples to use for future research studies.

To our knowledge, there are no extra risks involved in receiving one of the randomized standard protocol arms, nor in receiving the new drugs Inotuzumab and Blinatumomab. Side-effects are not different from the currently used standard treatment in relapsed ALL. If, however, your child experiences serious side-effects, an alternative treatment plan will be devised by the child's consultant team.

During chemotherapy, an adolescent girl should not become pregnant nor should an adolescent boy impregnate his partner(s). Unborn babies exposed to chemotherapy have a high risk of developing malformations. Therefore, in case of sexual activity, safe forms of contraception must be used

We cannot necessarily predict that the new treatment is better than standard treatment. However, there are some benefits to taking part in a clinical trial:

• Your child may receive treatment with the potential to improve outcome which would not be accessible to him/her outside of this study. The information which will be collected from your child will help to improve future treatment for children with relapsed ALL – just like today's knowledge is based on the outcome of previous clinical trial.
• If the new drug proves to be effective, it will be licensed for the pharmaceutical market and recommended for treatment of all children with relapsed ALL.
• National and international experts have worked together to develop the IntReALL 2020 study and your child will be very closely monitored throughout.

First, take time to fully understand the information about the IntReALL 2020 study. Please do not hesitate to ask questions.

Then, we advise to consider both available options: Standard treatment and participation in the IntReALL 2020 study.

Finally, discuss the proposed study with your spouse/partner, with your child's other parent/guardian, and with your child.

Decision-making is a challenging process. If you have different positions, it is important to listen to each other’s arguments and concerns. You may wish to discuss the different views with a consultant, counsellor or psychologist. If your child does not want to take part in the study, but you do, try to understand the underlying causes of his/her objections. Some children do not fully understand the details of the treatment, others have irrational fears and need reassurance. Some children who have experienced multiple relapses may be aware of their very difficult situation and wish to maintain the present quality of life by receiving palliative care instead of another treatment.

Please keep in mind that in most European countries, adolescents older than 14 years will be informed about the IntReALL study and are expected to sign a consent form. In some countries, their decision have priority over those of their parents.

Please do not hesitate to seek help from a counsellor or psychologist to facilitate your family’s decision-making process. We want you to feel that you are making the most appropriate decision for your child and your family. The psycho-social team of the hospital or ward will be able to assist you and your child.

You are under no obligation to take part in this study. If you decide that you do not wish your child to participate, he/she will still receive the presently best possible care.

You and your child can withdraw your consent to the study at any time, without giving a reason. Your child will then be entitled to the standard treatment and best possible care.

By law, all information about your child and his/her illness will be kept strictly confidential. In addition, all data related to your child’s participation in the IntReALL study will be used solely for research purposes, or be given to your country’s regulatory body (e.g., the Office of National Statistics). Should this be the case, all your child’s personal details will be removed before the data is analysed to that he/she cannot be identified by name, address or medical details.

If you have any questions about the study, please do not hesitate to ask anyone of the medical or research team at your treatment centre or contact the study’s representatives (contact details found here).

If you have any questions about the storage of your data, you should contact the study’s representatives.

If you have any complaints about any aspect of the way you or your child have been approached or treated during the course of this study, please feel free to discuss your concerns with the treatment team or contact the local hospital’s complain department.

After the end of the study, medical researchers have the responsibility to publish the results and make them widely known so that cancer treatment can improve. Results are published in medical journals, presented at national and international conferences, and will also be reported on intreall2020.eu.