We founded the RESOLVE consortium (Residual disease assessment in hematologic malignancies to improve patient-relevant outcomes across Europe) to better understand the role of MRD for personalized treatment decisions. The trial investigates whether treatment intensity can be safely reduced in MRD negative patients after an initial treatment, and thereby reduce side effects and economic burden, and increase patients’ quality of life.
Patients
Why is the trial being conducted?
Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a type of cancer that affects early forms of blood cells. These abnormal blood cells grow rapidly, accumulate in the bone marrow, and disrupt the normal production of blood cells. Low levels of blood cells increase the risk of infections, cause anemia leading to fatigue, and result in a condition called thrombocytopenia, which raises the chances of bleeding. Infections are the main cause of death in people with AML, while a smaller number of patients may experience fatal bleeding events. AML is the most common form of acute leukemia in adults. Current treatment strategies comprise of induction and consolidation chemotherapy and may also include allogeneic hematopoietic cell transplantation.
While induction therapy should induce an initial response, consolidation therapy has the intention of preventing disease progression or relapse. Current consolidation therapies can have side effects and may impact the patient’s quality of life. The choice of therapies and their intensities for a patient is dependent on age, comorbidities, nature of AML and other factors. Recent evidence has suggested, that certain AML patients with specific disease characteristics might not need the most intense treatment currently available, allogeneic hematopoietic cell transplantation. Therefore, it would help to identify those patients beforehand and reduce their treatment intensity accordingly.
Current treatment guidelines for acute leukemias suggest the quantification of residual disease (measurable residual disease, or MRD) by a technology called flow cytometry, for this identification approach. Measurable residual disease describes the presence of a very small number of leukemia cells in the body after a treatment that cannot be detected by conventional diagnostic tests, but may influence relapse risk. While flow cytometry is already widely utilized in leukemia diagnosis and subtype differentiation, as well as therapeutic decision-making for some leukemia subtypes, there is still a debate about how flow-cytometry-assessed MRD results can be used to guide treatment decisions in patients with AML. Mounting evidence suggests that ELN intermediate risk AML patients with a negative MRD result – those with residual disease below a certain detection limit following initial treatment – may be at a lower risk of relapse. We therefore hypothesize that treatment intensity can be safely reduced in those patients, with chemotherapy instead of allogeneic transplantation, and thereby reduce their side effects, economic burden, and increase their quality of life. This trial will prove the effectiveness of reducing treatment intensity in MRD-negative AML patients with intermediate risk disease in a real-world setting with our main objective being to show that overall survival with chemotherapy will be comparable to overall survival with allogeneic transplantation.
Chronic Lymphocytic Leukemia
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SSL) is a type of blood cancer that affects cells of the lymphoid system. In CLL/SLL, an immune cell undergoes malignant changes and divides uncontrollably. CLL/SLL is the most prevalent form of adult leukemia in the Western world, typically diagnosed around the age of 72 and affecting more than 41,000 individuals annually in Europe. At the time of diagnosis only a minority of patients with CLL require treatment, but the need for treatment may arise in the following years. Thus, patients with CLL receive life-long monitoring. When the disease progresses with for example enlarged lymph nodes, anemia, low platelet values, or an enlarged spleen, current treatment guidelines recommend targeted therapies with so called BTK inhibitors (BTKi), BCL2 inhibitors (BCL2i), and anti-CD20 monoclonal antibodies (MoAb).
BTK inhibitors work like a lock and key, blocking signals that help leukemia cells grow. BCL2 inhibitors help by stopping a protein that helps leukemia cells survive, making it easier for the body to fight the disease. Anti-CD20 monoclonal antibodies act by tagging the leukemia cells, helping the immune system find and attack them more easily. These medicines are part of newer and effective treatments for CLL/SLL. They are generally safe, yet still carry the risk of various significant adverse events, including diarrhea, fatigue, infections, bleeding, cardiovascular complications and others. Besides impacting the patient’s quality of life, they also pose a financial burden on the health system.
CLL/SLL showcases a highly varied clinical journey: some patients may never need treatment, while others encounter an aggressive form of the disease with frequent relapses. Patients meeting specific criteria indicating progression require treatment, while asymptomatic patients with low disease burden are usually observed following an active monitoring approach.
Available treatments may be administered continuously until disease progression or unacceptable toxicity (like BTKi monotherapy) or for fixed duration (like the combination of BCL2i+anti-CD20 MoAb or BCL2i+BTKi). Measurable residual disease describes the presence of a very small number of leukemia cells in the body after a treatment that cannot be detected by conventional diagnostic tests, but may influence relapse risk. While MRD is already widely utilized in monitoring the response of patients with hematologic malignancies to the administered treatment, there is still a debate about how MRD results can be used to guide treatment decisions in patients with CLL/SLL. Mounting evidence suggests that patients with CLL/SLL and undetectable MRD (uMRD) – those with residual disease below a certain detection threshold following initial treatment – may be at a lower risk for relapse, even without prolonged therapy. The RESOLVE trial will evaluate whether a shorter duration of treatment in patients without residual disease (undetectable MRD) is associated with a lower burden of adverse events without compromising on efficacy.
If you are interested in participating please contact a trial site close to you.
Participating Trial Sites
Acute Myeloid Leukemia
Augsburg – Universitätsklinik
Dept. Hematology/Oncology
Stenglinstr. 2, 86156 Augsburg
Berlin – Charité
Dept. Hematology/Oncology
Augustenburger Platz 1, 13353 Berlin
Braunschweig- Städt. Klinikum
Dept. Hematology/Oncology
Freisestr. 9/10, 38118 Braunschweig
Dresden – Universitätskrankenhaus
Dept. Hematology/Oncology
Fiedlerstraße 19, 1307 Dresden
Erfurt – Helios Klinikum
Dept. Hematology/Oncology
Nordhäuser Straße 74, 99089 Erfurt
Essen – Universitätsklinik
Dept. Hematology/Oncology
Hufelandstraße 55, 45147 Essen
Frankfurt – Universitätsklinik
Dept. Hematology/Oncology
Theodor-Stern-Kai 7, 60590 Frankfurt
Greifswald- Universitätsmedizin
Dept. Hematology/Oncology
Sauerbruchstr. , 17475 Greifswald
Halle – Universitätsklinikum
Dept. Hematology/Oncology
Ernst-Grube-Str. 40, 6120 Halle
Hamburg-Eppendorf- Universitätsklinikum
Dept. Hematology/Oncology
MARTINISTRASSE 52, Campus Forschung N27, 20246 Hamburg
Hannover- Medizinische Hochschule
Dept. Hematology/Oncology
Carl-Neuberg-Str. 1, 30625 Hannover
Kiel – Universitätsklinik Schleswig-Holstein
Dept. Hematology/Oncology
Arnold-Heller-Straße 3, 24105 Kiel
Köln- Universitätsklinik
Dept. Hematology/Oncology
Kerpener Str. 62, 50937 Köln
Leipzig – Universitätsklinikum
Dept. Hematology/Oncology
Liebigstr. 20, 04103 Leipzig
Magdeburg – Universitätsklinikum
Dept. Hematology/Oncology
Leipziger Str. 44, 39120 Magedburg
München- LMU Universitätsklinik
Dept. Hematology/Oncology
Marchioninistr. 15, 81377 München
Münster – Universitätsklinikum
Dept. Hematology/Oncology
Albert-Schweitzer-Straße 33, 48149 Münster
Regensburg – Universitätsklinikum
Dept. Acute leukaemia, stem cell transplantation and immunotherapy
Franz-Josef-Strauß-Allee 11, 93053 Regensburg
Rostock – Universitätsmedizin
Dept. Hematology/Oncology
Ernst-Heydemann-Str. 6, 18057 Rostock
Schwerin – Helios Klinikum
Dept. Hematology/Oncology
Wismarsche Straße 393 – 397, 19055 Schwerin
Tübingen- Universität
Dept. Hematology/Oncology
Ottfried-Müller-Str. 10, 72076 Tübingen
Ulm – Universität
Dept. Hematology/Oncology
Albert-Einstein-Allee 23, 89081 Ulm
Gdansk – Medical University – University Medical Center
Dept. Hematology/Oncology
Ul. Smoluchowskiego 17, 80-214 Gdansk
Gliwice – National Research Institute
Dept. Hematology/Oncology
Ul. Wybrzeże Armii Krajowej 15, 44-101 Gliwice
Lodz – Medical University
Dept. Hematology/Oncology
Ul. Pabianicka 62, 93-513 Łódź
Katowice – Silesian Medical University
Dept. Hematology/Oncology
Ul. Dąbrowskiego 25, 40-032 Katowice
Krakow – Jagiellonian University
Dept. Hematology/Oncology
Ul. Jakubowskiego 2, Krakow
Poznan – Medical University
Dept. Hematology/Oncology
Ul. Szamarzewskiego 82/84, 60-569 Poznan
Warszawa – Institute of Hematology and Transfusion Medicine
Dept. Hematology/Oncology
Ul. Indiry Gandhi 14 02-776 Warszawa
Warszawa – Medical University of Warsaw
Dept. Hematology/Oncology
Ul. Banacha 1A, Warszawa
Wroclaw – Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu, Klinika Hematologii
Dept. Nowotworów Krwi i Transplantacji Szpiku
ul. Wybrzeże L. Pasteura 4, 50-367 Wrocław
Athens – Evanggelismos Hospital
Athens – Attikon University General Hospital
Athens – Laikon Hospital
Thessaloniki – G. Papanikolaou Hospital
Haifa – Rambam Medical Center
Dr. Avi Friech
email: a_frisch@rambam.health.gov.il
Haifa – Beni Zion Medical Center
Prof. Tamar Tadmor
email: tamar.tadmor@b-zion.org.il
Jerusalem – Hadassah medical Center
Dr. Boaz Nahmias
email: Boazn@hadassah.org.il
Jerusalem – Shaare Zedek medical center
Prof. Yishai Ofran
email: yofran@szmc.org.il
Petach Tikvah –Rabin medical center – Beilinson
Prof. Ofir Wolach
email: ofirw@clalit.org.il
Tel Aviv –Sourasky medical center – Ichilov
Dr. Yakir Moshe
email: yakirm@tlvmc.gov.il
Latina – OSPEDALE SANTA MARIA GORETTI
Dept. UOC EMATOLOGIA
Meldola – I.R.S.T. SRL IRCCS
Dept. SC ONCOLOGIA MEDICA
Milano – ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA
Dept. SC EMATOLOGIA
Modena – AOU DI MODENA
Dept. SC EMATOLOGIA
Palermo -AO OSPEDALI RIUNITI VILLA SOFIA CERVELLO
Dept. UO EMATOLOGIA AD INDIRIZZO ONCOLOGICO
Perugia – OSPEDALE S. MARIA DELLA MISERICORDIA
Dept. EMATOLOGIA E TRAPIANTO MIDOLLO OSSEO
Pescara – ASL PESCARA, PRESIDIO OSPEDALIERO ‘SPIRITO SANTO’
Dept. UOC EMATOLOGIA CLINICA
Roma – UNIVERSITÀ DEGLI STUDI DI ROMA “SAPIENZA”
Dept. U.O.C. EMATOLOGIA
Roma – AOU POLICLINICO TOR VERGATA
UOC TRAPIANTO CELLULE STAMINALI
Bordeaux – CHU – Hôpital Haut Leveque
Département d’Hématologie
Grenoble – CHU de Grenoble
Département d’Hématologie
Rennes – CHU – Hôpital Pontchaillou
Département d’Hématologie
Toulouse – IUCT Oncopole
Département d’Hématologie
Chronic Lymphocytic Leukemia
Köln- Universitätsklinik
50924 Köln
Paderborn – Brüderkrankenhaus
Husener Str. 46, 33098 Paderborn
Rostock – Universitätsmedizin
Ernst-Heydemann-Str. 6, 18057 Rostock
Kiel Universitätsklinikum Schleswig Holstein Campus
Campus Kiel – Arnold-Heller-Straße 3, 24105 Kiel
Halle – Universitätsklinikum Halle
Erfurt Helios Klinikum
München –Klinik Schwabing
Gliwice -Narodowy Instytut Onkologii im. Marii Skłodowskiej – Curie, Państwowy Instytut Badawczy Oddział w Gliwicach
Klinika Transplantacji Szpiku i Onkohematologi
ul. Wybrzeże Armii Krajowej 15, 44 – 102 Gliwice
Lodz – Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi, Oddział – Klinika Hematologii.
Hematologii i Transplantologii
UL, Ciolkowskiego 2, 93-510 Lodz
Lublin Uniwersytet Medyczny w Lublinie
Hematoonkologii i Transplantacji Szpiku, ul.
Klinika Staszica 11 20-081 Lublin
Warszaw – Centralny Szpital Kliniczny Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
Klinika Hematologii/Transplantologii i Chorób Wewnętrznych
ul. Banacha 1A, 02 – 097 Warszawa
Wroclaw Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu, Klinika Hematologii
Nowotworów Krwi i Transplantacji Szpiku
ul. Wybrzeże L. Pasteura 4, 50-367 Wrocław
Alexandroupoulis – University
Athens – University of Athens
Ioannina – University
Thessaloniki – G. Papanikolaou Hospital
Thessaloniki – AHEPA Hospital
Haifa – Rambam Medical Center
Dr. Riva Fineman
email: r_fineman@rambam.health.gov.il
Haifa – Beni Zion Medical Center
Prof. Tamar Tadmor
email: tamar.tadmor@b-zion.org.il
Jerusalem – Hadassah Medical Center
Prof. Netta Goldshimt
email: neta@hadassah.org.il
Jerusalem – Shaare Zedek medical center
Prof. Yishai Ofran
email: yofran@szmc.org.il
Petach Tikvah – Rabin medical center – Beilinson
Tel Aviv – Sourasky medical center – Ichilov
Prof. Yair Herishanu
email: yairh@tlvmc.gov.il
Kfar Saba –Meir medical center
Dr. Gilad Itchaki
email: giladi@clalit.org.il
Milano – Ospedale San Raffaele
Novara – AOU MAGGIORE DELLA CARITA’ DI NOVARA
Padova – AOU DI PADOVA
UO EMATOLOGIA
Perugia – OSPEDALE S. MARIA DELLA MISERICORDIA
Dept. EMATOLOGIA E TRAPIANTO MIDOLLO OSSEO
Pescara – ASL PESCARA, PRESIDIO OSPEDALIERO ‘SPIRITO SANTO’
Dept. UOC EMATOLOGIA CLINICA
Grenoble – CHU de Grenoble
Département d’Hématologie
Nantes – CHU – Hôtel Dieu
Département d’Hématologie
Rennes – CHU – Hôpital Pontchaillou
Département d’Hématologie
Toulouse – IUCT Oncopole
Département d’Hématologie