Acute Myeloid LeukemiaPhase 2TEAMNCT04173585
TEAM-Trial: Targeting Epigenetic Therapy Resistance in AML With Bortezomib
A Phase 2 study testing Bortezomib and Gemtuzumab Ozogamicin in people with Acute Myeloid Leukemia, run by University Hospital Heidelberg at 1 site in Germany.
Trial summary
The long-term outcome of patients with acute myeloid leukemia (AML) remains poor, with less than 30% of patients achieving long lasting remission or cure. This poor outcome is largely due to refractoriness to induction chemotherapy as well as relapses during and after completion of intensive induction and… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Bortezomib and Gemtuzumab Ozogamicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteGermany
- Study dates
- 22 Oct 2019to 24 Mar 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with confirmed diagnosis of AML according to WHO-2016 [27] (except acute promyelocytic leukemia) either de novo AML, AML after preceding myelodysplastic or myeloproliferative syndrome (MDS/MPD), and therapy related AML (t-AML) after previous cytotoxic therapy or radiation are eligible either refractory (A) to first line chemotherapy or in first relapse (B), also after stem cell transplantation. FLT3-ITD status, cytogenetics (refractory and relapsed patients), in addition status of core-binding-factor as well as double mutant CEBPA in relapsed patients must be available.
- Refractory to induction therapy is defined as no CR, CRi (according to standard criteria) [4] after 2 intensive induction cycles of at least 7 days of cytarabine 100-200 mg/m² continuously or an equivalent regimen with cytarabine with total dose not less than 700 mg/m² per cycle and 3 days of an anthracycline/ anthraquinone (e.g. daunorubicin, idarubicin).
- Relapsed after first line therapy is defined as relapsed AML after CR or CRi (according to standard criteria) after at least one intensive induction and consolidation (including intensive chemotherapy and/or hematopoietic cell transplantation) therapy.
- ECOG performance status ≤ 2
- Discontinuation of prior AML treatment before the start of study treatment (except hydroxyurea or other treatment to control hyperleukocytosis) for at least 10 days for cytotoxic agents and 5 half-lives for non-cytotoxic/ investigational drug treatment preceding the first dose of trial medications
- Age ≥ 18 years
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- Pregnancy and childbearing potential:
- Non-pregnant and non-nursing women of childbearing potential must have a negative serum or urine ß-HCG pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration ("Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months).
- Female patients of reproductive age must agree to avoid getting pregnant while on therapy.
- Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin highly effective methods of birth control during study and for at least 7 months after end of treatment.
- Men must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy and must agree to avoid to father a child during study and until 6 months after end of study/treatment.
- Willingness of patient to adhere to protocol specific requirements and capacity to give written informed consent
- Ability of patient to understand the character and individual consequences of clinical Trial
- Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out
Who cannot join
- Acute promyelocytic leukemia (AML M3)
- Acute myeloid leukemia previously treated with gemtuzumab ozogamicin
- Hyperleukocytosis (leukocytes > 30,000/μl) at the time of study entry. These patients should be treated with hydroxyurea and / or receive leukocytapheresis treatment according to routine practice and are only allowed to enter into the study when leukocyte counts of 30,000/μl or below are reached. If hydroxyurea is not sufficient to control hyperleukocytosis i.v. application of 100 mg cytarabine continuously over 24 hours may be discussed with the coordinating investigator or the scientific coordinator
- Known central nervous system manifestation of AML
- uncontrolled or significant cardiovascular disease, including any of the following:
- History of heart failure NYHA class 3 or 4
Show all 26Show fewer
- Left ventricular ejection fraction (LVEF) ≤ 40% by echocardiogram
- History of uncontrolled angina pectoris or myocardial infarction within 12 months prior to screening
- History of second (Mobitz II) or third degree heart block or any cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
- Pregnant or nursing woman
- Chronically impaired renal function (creatinine clearance < 30 ml / min)
- Inadequate liver function (ALT and AST ≥ 2 x ULN), total bilirubin ≥ 1.5 x ULN
- Known liver cirrhosis or history of veno-occlusive disease (VOD)
- HIV infection and/or active hepatitis B or C infection (active hepatitis B defined by HBs Ag positivity, active hepatitis C defined by positive virus load)
- Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy
- Uncontrolled active infection
- Concurrent malignancies other than AML with an estimated life expectancy of less than two years
- Known hypersensitivity to cytarabine (AraC) (not including drug fever, conjunctivitis or exanthema)
- Known hypersensitivity to bortezomib, boron or mannitol
- Isolated extramedullary manifestation of AML
- Patients within 100 days after allogeneic stem cell transplantation at the time of Screening
- Patients with clinically relevant Graft-versus-Host-Disease (GvHD) requiring initiation of treatment or treatment escalation within 21 days prior to Screening
- Patients with pre-existing severe neuropathy
- Acute diffuse infiltrative pulmonary disease
- Pericardial disease
- Expected incompliance of patient
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Hospital Heidelberg, Internal Medicine V
Heidelberg, Baden-Wurttemberg, 69120
About this study
Official title: TEAM-Trial: Targeting Epigenetic Therapy Resistance in AML With Bortezomib: A Multi-centre Matched Threshold Crossing Phase II Approach
The long-term outcome of patients with acute myeloid leukemia (AML) remains poor, with less than 30% of patients achieving long lasting remission or cure. This poor outcome is largely due to refractoriness to induction chemotherapy as well as relapses during and after completion of intensive induction and consolidation therapy. In patients with refractory/relapsed AML hematopoietic cell transplantation (allo-HCT) is currently the only treatment option offering a prospect of cure but outcome is heavy influenced by the remission status before allo-HCT. Therefore, patients are typically treated with salvage regimens based on high dose cytarabine (HiDAC) combined with mitoxantrone, fludarabine or idarubicin. Nevertheless, the remission rates remain poor and currently there is no accepted standard salvage regimen. Recent studies indicate that combination chemotherapy including HiDAC and gemtuzumab ozogamicin (GO) at a dose of 3 mg/m² leads to improved response rates in refractory AML.
Proteasome inhibition with bortezomib appears to be a promising treatment strategy to restore chemo-sensitivity via EZH2 stabilisation.
Read more
This study aims at improving response rates in refractory/ relapsed AML by combining high dose cytarabine, gemtuzumab ozogamicin (GA) and bortezomib (B).
During this phase II study efficacy of B-GA is assessed in comparison to matched historical controls using the Matched Threshold Crossing (MTC)-approach. If results are promising, a subsequent randomized phase III study is intended to assess the efficacy of GA with or without bortezomib.
Read the detailed description
Acute Myeloid Leukemia (AML) is a clonal malignant disorder which is characterized by the expansion of leukemic blasts in the bone marrow and the peripheral blood, which goes along with a suppression of normal hematopoiesis including granulopoiesis, erythropoiesis and thrombocytopoiesis. The prognosis is largely determined by cytogenetic and molecular risk factors, age, performance status and antecedent Myelodysplastic Syndrome (MDS).
With the exception of old and frail patients, most AML patients are eligible for intensive chemotherapy, which is given in curative intent consisting of induction and consolidation therapy. However, despite intensive therapy, the long-term outcome of AML patients remains poor, with less than 30% of patients achieving long lasting remission and even cure. This poor outcome is largely due to refractoriness to induction chemotherapy as well as relapses during and after completion of intensive induction and consolidation therapy. Regarding refractoriness, about 20-30% of AML patients under the age of 60 years and about 50% of older patients fail to attain complete remission (CR) following cytarabine plus anthracycline based standard induction therapy. Regarding relapses, even patients having achieved complete remission are at a high risk of relapse, particularly within the first two years after completion of chemotherapy.
In patients with blast persistence after induction therapy or relapse, allogeneic hematopoietic cell transplantation (allo-HCT) is currently the only treatment strategy to offer the prospect of cure. Outcome of allo-HCT is heavily influenced by the remission state before allo-HCT. With the aim to induce a complete remission (CR) before allo-HCT, salvage chemotherapy regimens are administered in refractory/relapsed patients. Typically, these salvage regimens are based on high dose cytarabine (HiDAC), which is frequently combined with either mitoxantrone (HAM regimen) or fludarabine plus idarubicin (idaFLA regimen). Currently, there is no commonly accepted standard salvage regime, but a large individual patient data meta-analysis and single arm phase-II studies suggest that combination chemotherapy including HiDAC and gemtuzumab ozogamicin, an antibody drug conjugate, are very effective. Since patients with refractory or relapsed AML are candidates for allo-HCT, the main purpose of the salvage regimen is to bridge patients to allo-HCT with induction of a CR before allo-HCT. Therapy resistance in cancer is still poorly understood. Beyond genetic aberrations epigenetic mechanisms are important components of resistance to cancer therapy. Recently, the investigators discovered an epigenetic therapy resistance mechanism in AML (Figure 1). This mechanism might be relevant in up to 50% of relapsed/refractory AML patients. This epigenetic mediated resistance can be successfully overcome in in vitro models by proteasome inhibition. Currently, relapsed and refractory r/r-AML still carries a dismal prognosis. In this multicentre, phase II trial the investigators will analyze efficacy of a novel therapy regimen for r/r-AML.
As detailed above, combination-chemotherapy including GO and HiDAC based chemotherapy is an effective regimen in r/r-AML.
Proteasome inhibitors can restore EZH2 protein levels in vitro and in vivo. The restoration of EZH2 significantly improved efficacy of anti-leukemic therapy. Based on the data mentioned above we combine the treatment efficacy of GO plus cytarabine based chemotherapy with the proteasome inhibitor bortezomib in the B-GA regimen. With such an approach the investigators believe that they can substantially improve treatment results in r/r-AML. Part of the study is a pre-specified biomarker analysis for EZH2 restoration after bortezomib exposure in vitro and in vivo. Accordingly, we will be able to determine whether EZH2 restoration after bortezomib exposure is associated with response and outcome. There have been rare reports of acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome (ARDS) in patients receiving bortezomib. In particular, 2 patients with r/r-AML given high-dose cytarabine (2 g/m²/day) by continuous infusion in combination with daunorubicin and bortezomib died of ARDS early in the course of therapy. However, in several trials evaluating the combination of bortezomib with standard and high-dose cytarabine in AML patients no toxicity signal was detected, especially with respect to ARDS.
Taken together, the rationale for this trial is based on the high unmet clinical need and strong in vitro evidence.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Bortezomib, Gemtuzumab Ozogamicin
- Keywords
- Acute Myeloid Leukemia, therapy resistance, refractory/relapsed, AML
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
Bortezomib is a small molecule dipeptide binding the catalytic site of the 26 S proteasome. It acts as a potent, reversible, and specific inhibitor of proteasomes and thus impairs the degradation of ubiquitinated proteins. It has demonstrated anti-neoplastic activity in myeloma and lymphoma. It is approved and widely used in multiple myeloma both for first line treatment and relapsed patients.
Gemtuzumab OzogamicinDrug
Also called Mylotarg
Gemtuzumab Ozogamicin is a monoclonal antibody directed against the myeloid surface antigen CD33. The antibody is linked to calicheamicin which serves as cytotoxic agent. For years, gemtuzumab ozogamicin has been tested in clinical AML trials. Though withdrawn from the US market in 2010, FDA approval was granted in September 2018, EU approval in April 2018 based on encouraging results from recent clinical trials using enhanced dosing schedules.
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib-Gemtuzumab Ozogamicin Treatment | Experimental | one cycle of combined chemotherapy:
* Bortezomib (1.3 mg/m2) sc on day 1 and 3. Dose will be given 3 hours prior to Cytarabine on day 1 and 3
* Cytarabine (1g/m² twice daily) iv over 3 hours on day 1, 2 and 3 Gemtuzumab Ozogamicin (3 mg/m²,up to a maximum of one 5 mg vial) iv over 2 hours on day 1 after first dose of Cytarabine and day 4
* Pegfilgrastim 6 mg sc on day 8 (optional) Receives: Drug: Bortezomib; Drug: Gemtuzumab Ozogamicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
CR/CRi rate
Primary endpoint is the CR/CRi rate (response rate), defined as the proportion of patients achieving a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) according to ELN 2017 criteria after B-GA treatment.
Measured: two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2019
- Study start22 Oct 2019
- Primary completion28 Feb 2023
- Study completion24 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by University Hospital HeidelbergThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Simon's Optimal Two-Stage Design: The Matched Threshold Crossing (MTC) Design
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Heidelberg
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Tumor Diseases, Heidelberg
- Responsible party
- Principal investigator, Prof. Dr. Richard F Schlenk, University Hospital Heidelberg
- Investigators
- Carsten Müller-Tidow, Prof., MD, Principal investigator, Medical Director of Internal Medicine V, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04173585
- Sponsor's protocol ID
- NCT-2017-0530
- Acronym
- TEAM
- Status last verified
- Mar 2023
- First submitted
- 20 Nov 2019
- Last updated
- 27 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TEAM-Trial: Targeting Epigenetic Therapy Resistance in AML With Bortezomib: A Multi-centre Matched Threshold Crossing Phase II Approach
- ClinicalTrials.gov ID
- NCT04173585
- Acronym / sponsor ID
- TEAM / NCT-2017-0530
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Acute Myeloid Leukemia, therapy resistance, refractory/relapsed, AML
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University Hospital HeidelbergUniversity, hospital or other
- Collaborators
- National Center for Tumor Diseases, Heidelberg
- Study start
- 22 Oct 2019 (actual)
- Primary completion
- 28 Feb 2023 (actual)
- Study completion
- 24 Mar 2023 (actual)
- First posted
- 22 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The long-term outcome of patients with acute myeloid leukemia (AML) remains poor, with less than 30% of patients achieving long lasting remission or cure. This poor outcome is largely due to refractoriness to induction chemotherapy as well as relapses during and after completion of intensive induction and consolidation therapy. In patients with refractory/relapsed AML hematopoietic cell transplantation (allo-HCT) is currently the only treatment option offering a prospect of cure but outcome is heavy influenced by the remission status before allo-HCT. Therefore, patients are typically treated with salvage regimens based on high dose cytarabine (HiDAC) combined with mitoxantrone, fludarabine or idarubicin. Nevertheless, the remission rates remain poor and currently there is no accepted standard salvage regimen. Recent studies indicate that combination chemotherapy including HiDAC and gemtuzumab ozogamicin (GO) at a dose of 3 mg/m² leads to improved response rates in refractory AML.
Proteasome inhibition with bortezomib appears to be a promising treatment strategy to restore chemo-sensitivity via EZH2 stabilisation.
This study aims at improving response rates in refractory/ relapsed AML by combining high dose cytarabine, gemtuzumab ozogamicin (GA) and bortezomib (B).
During this phase II study efficacy of B-GA is assessed in comparison to matched historical controls using the Matched Threshold Crossing (MTC)-approach. If results are promising, a subsequent randomized phase III study is intended to assess the efficacy of GA with or without bortezomib.
Detailed description
Acute Myeloid Leukemia (AML) is a clonal malignant disorder which is characterized by the expansion of leukemic blasts in the bone marrow and the peripheral blood, which goes along with a suppression of normal hematopoiesis including granulopoiesis, erythropoiesis and thrombocytopoiesis. The prognosis is largely determined by cytogenetic and molecular risk factors, age, performance status and antecedent Myelodysplastic Syndrome (MDS).
With the exception of old and frail patients, most AML patients are eligible for intensive chemotherapy, which is given in curative intent consisting of induction and consolidation therapy. However, despite intensive therapy, the long-term outcome of AML patients remains poor, with less than 30% of patients achieving long lasting remission and even cure. This poor outcome is largely due to refractoriness to induction chemotherapy as well as relapses during and after completion of intensive induction and consolidation therapy. Regarding refractoriness, about 20-30% of AML patients under the age of 60 years and about 50% of older patients fail to attain complete remission (CR) following cytarabine plus anthracycline based standard induction therapy. Regarding relapses, even patients having achieved complete remission are at a high risk of relapse, particularly within the first two years after completion of chemotherapy.
In patients with blast persistence after induction therapy or relapse, allogeneic hematopoietic cell transplantation (allo-HCT) is currently the only treatment strategy to offer the prospect of cure. Outcome of allo-HCT is heavily influenced by the remission state before allo-HCT. With the aim to induce a complete remission (CR) before allo-HCT, salvage chemotherapy regimens are administered in refractory/relapsed patients. Typically, these salvage regimens are based on high dose cytarabine (HiDAC), which is frequently combined with either mitoxantrone (HAM regimen) or fludarabine plus idarubicin (idaFLA regimen). Currently, there is no commonly accepted standard salvage regime, but a large individual patient data meta-analysis and single arm phase-II studies suggest that combination chemotherapy including HiDAC and gemtuzumab ozogamicin, an antibody drug conjugate, are very effective. Since patients with refractory or relapsed AML are candidates for allo-HCT, the main purpose of the salvage regimen is to bridge patients to allo-HCT with induction of a CR before allo-HCT. Therapy resistance in cancer is still poorly understood. Beyond genetic aberrations epigenetic mechanisms are important components of resistance to cancer therapy. Recently, the investigators discovered an epigenetic therapy resistance mechanism in AML (Figure 1). This mechanism might be relevant in up to 50% of relapsed/refractory AML patients. This epigenetic mediated resistance can be successfully overcome in in vitro models by proteasome inhibition. Currently, relapsed and refractory r/r-AML still carries a dismal prognosis. In this multicentre, phase II trial the investigators will analyze efficacy of a novel therapy regimen for r/r-AML.
As detailed above, combination-chemotherapy including GO and HiDAC based chemotherapy is an effective regimen in r/r-AML.
Proteasome inhibitors can restore EZH2 protein levels in vitro and in vivo. The restoration of EZH2 significantly improved efficacy of anti-leukemic therapy. Based on the data mentioned above we combine the treatment efficacy of GO plus cytarabine based chemotherapy with the proteasome inhibitor bortezomib in the B-GA regimen. With such an approach the investigators believe that they can substantially improve treatment results in r/r-AML. Part of the study is a pre-specified biomarker analysis for EZH2 restoration after bortezomib exposure in vitro and in vivo. Accordingly, we will be able to determine whether EZH2 restoration after bortezomib exposure is associated with response and outcome. There have been rare reports of acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome (ARDS) in patients receiving bortezomib. In particular, 2 patients with r/r-AML given high-dose cytarabine (2 g/m²/day) by continuous infusion in combination with daunorubicin and bortezomib died of ARDS early in the course of therapy. However, in several trials evaluating the combination of bortezomib with standard and high-dose cytarabine in AML patients no toxicity signal was detected, especially with respect to ARDS.
Taken together, the rationale for this trial is based on the high unmet clinical need and strong in vitro evidence.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Simon's Optimal Two-Stage Design: The Matched Threshold Crossing (MTC) Design
| Arm | Type | Receives |
|---|---|---|
| Bortezomib-Gemtuzumab Ozogamicin Treatment | Experimental | Drug: Bortezomib, Drug: Gemtuzumab Ozogamicinone cycle of combined chemotherapy: * Bortezomib (1.3 mg/m2) sc on day 1 and 3. Dose will be given 3 hours prior to Cytarabine on day 1 and 3 * Cytarabine (1g/m² twice daily) iv over 3 hours on day 1, 2 and 3 Gemtuzumab Ozogamicin (3 mg/m²,up to a maximum of one 5 mg vial) iv over 2 hours on day 1 after first dose of Cytarabine and day 4 * Pegfilgrastim 6 mg sc on day 8 (optional) |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients with confirmed diagnosis of AML according to WHO-2016 [27] (except acute promyelocytic leukemia) either de novo AML, AML after preceding myelodysplastic or myeloproliferative syndrome (MDS/MPD), and therapy related AML (t-AML) after previous cytotoxic therapy or radiation are eligible either refractory (A) to first line chemotherapy or in first relapse (B), also after stem cell transplantation. FLT3-ITD status, cytogenetics (refractory and relapsed patients), in addition status of core-binding-factor as well as double mutant CEBPA in relapsed patients must be available.
- Refractory to induction therapy is defined as no CR, CRi (according to standard criteria) [4] after 2 intensive induction cycles of at least 7 days of cytarabine 100-200 mg/m² continuously or an equivalent regimen with cytarabine with total dose not less than 700 mg/m² per cycle and 3 days of an anthracycline/ anthraquinone (e.g. daunorubicin, idarubicin).
- Relapsed after first line therapy is defined as relapsed AML after CR or CRi (according to standard criteria) after at least one intensive induction and consolidation (including intensive chemotherapy and/or hematopoietic cell transplantation) therapy.
- ECOG performance status ≤ 2
- Discontinuation of prior AML treatment before the start of study treatment (except hydroxyurea or other treatment to control hyperleukocytosis) for at least 10 days for cytotoxic agents and 5 half-lives for non-cytotoxic/ investigational drug treatment preceding the first dose of trial medications
Key exclusion criteria (26 listed)
- Acute promyelocytic leukemia (AML M3)
- Acute myeloid leukemia previously treated with gemtuzumab ozogamicin
- Hyperleukocytosis (leukocytes > 30,000/μl) at the time of study entry. These patients should be treated with hydroxyurea and / or receive leukocytapheresis treatment according to routine practice and are only allowed to enter into the study when leukocyte counts of 30,000/μl or below are reached. If hydroxyurea is not sufficient to control hyperleukocytosis i.v. application of 100 mg cytarabine continuously over 24 hours may be discussed with the coordinating investigator or the scientific coordinator
- Known central nervous system manifestation of AML
- uncontrolled or significant cardiovascular disease, including any of the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BortezomibAlso: VelcadeBortezomib is a small molecule dipeptide binding the catalytic site of the 26 S proteasome. It acts as a potent, reversible, and specific inhibitor of proteasomes and thus impairs the degradation of ubiquitinated proteins. It has demonstrated anti-neoplastic activity in myeloma and lymphoma. It is approved and widely used in multiple myeloma both for first line treatment and relapsed patients. | Drug | Bortezomib-Gemtuzumab Ozogamicin Treatment |
| Gemtuzumab OzogamicinAlso: MylotargGemtuzumab Ozogamicin is a monoclonal antibody directed against the myeloid surface antigen CD33. The antibody is linked to calicheamicin which serves as cytotoxic agent. For years, gemtuzumab ozogamicin has been tested in clinical AML trials. Though withdrawn from the US market in 2010, FDA approval was granted in September 2018, EU approval in April 2018 based on encouraging results from recent clinical trials using enhanced dosing schedules. | Drug | Bortezomib-Gemtuzumab Ozogamicin Treatment |
Primary outcome
CR/CRi rate
Time frame: two years
Primary endpoint is the CR/CRi rate (response rate), defined as the proportion of patients achieving a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) according to ELN 2017 criteria after B-GA treatment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carsten Müller-Tidow, Prof., MD principal investigator
Medical Director of Internal Medicine V, University Hospital Heidelberg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib and Gemtuzumab Ozogamicin in people with Acute Myeloid Leukemia, run by University Hospital Heidelberg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CR/CRi rate (time frame: two years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2023.