Acute Myeloid LeukemiaPhase 3GnGNCT04093505
Gemtuzumab Ozogamicin in Induction and Glasdegib in Postremission Therapy in Patients With AML (Acute Myeloid Leukemia)
A Phase 3 study testing Gemtuzumab Ozogamicin 147, Gemtuzumab Ozogamicin 1 and Glasdegib in people with Acute Myeloid Leukemia, run by University Hospital Heidelberg at 1 site in Germany.
Trial summary
The study is a randomized phase III trial with a 2x2 factorial design with measurable residual disease and event-free survival as primary endpoints, respectively. Patients are upfront randomized for the two induction schedules (Gemtuzumab Ozogamicin (GO)-147 versus GO-1; ratio 1:1) and for Glasdegib or Placebo (double… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Gemtuzumab Ozogamicin 147, Gemtuzumab Ozogamicin 1 and Glasdegib
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteGermany
- Study dates
- 1 Apr 2021to 23 Jun 2022
- Phase
- Phase 3
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with newly diagnosed acute myeloid leukemia according to the 2016 WHO classification
- Genetic and immunophenotypic assessment in one of the central laboratories
- No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis (≤ 7 days)
- Age ≥ 60 years, no upper age limit
- ECOG performance status (ECOG PS) ≤ 2. See appendix 18.1
- Pregnancy and childbearing potential:
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- Non-pregnant and non-nursing women of childbearing potential (WOCBP) must have a negative serum or urine 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.
- WOCBP must either commit to continued abstinence from heterosexual intercourse or begin one acceptable method of birth control (IUD, tubal ligation, or partner's vasectomy) during study and 6 months after end of study/treatment. Hormonal contraception is an inadequate method of birth control.
- 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 6 months after end of study/treatment
- Signed written informed consent
- Ability of patient to understand character and consequences of the clinical trial
Who cannot join
- AML with PML-RARA or BCR-ABL1
- Patients with known active central nervous system leukemia (assessed clinically).
- Prior treatment with a smoothened inhibitor (SMOi) and/or hypomethylating agent for AML. (Treatment of a preceding MDS (myelodysplastic syndrome) with HMA is not an exclusion criterion.)
- Inadequate renal function: creatinine > 1.5 x upper normal serum level; estimated creatinine clearance ≤30 ml/min (calculated using the standard method for the institution).
- Inadequate liver function: ALT and AST ≥ 2.5 x ULN), total bilirubin ≥ 1.5 x ULN; Alkaline phosphatase ≥ 2.5 x ULN. Known liver cirrhosis or history of veno-occlusive disease (VOD) or history of Sinusoidal Obstruction Syndrome (SOS)
- Uncontrolled hypertension; severe obstructive or restrictive ventilation disorder
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- Any one of the following ongoing or in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsades de pointes, arrhythmias (including sustained ventricular tachyarrhythmia), right or left bundle branch block and bifascicular block, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF NYHA III/IV), cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism; as well as bradycardia defined as <50 bpms
- QTc interval >470 msec using the Fredericia correction (QTcF).
- Uncontrolled infection
- Patients known to be refractory to platelet or packed red cell transfusions as per institutional guidelines, or who are known to refuse or who are likely to refuse blood product support.
- Patients with a "currently active" second malignancy other than non-melanoma skin cancer. Patients are not considered to have a "currently active" malignancy if they have completed therapy for more than one year and are considered by their physician to be at less than 30% risk of relapse within one year.
- Severe neurologic or psychiatric disorder interfering with ability of giving informed consent
- Known or suspected active alcohol or drug abuse
- Known positivity for HIV, active HBV, HCV, or hepatitis A infection
- Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy
- No consent for biobanking and for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician about study participation.
- Pregnancy and lactation
- History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
- Participation in a clinical study involving an investigational drug(s) (Phases 1-4) within 4 weeks prior to study entry.
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: Randomized Phase-III Study to Compare Two Schedules of Gemtuzumab Ozogamicin as Adjunct to Intensive Induction Therapy and to Compare Intensive Postremission Therapy Double Blinded With or Without Glasdegib in Older Patients With Newly Diagnosed AML
The study is a randomized phase III trial with a 2x2 factorial design with measurable residual disease and event-free survival as primary endpoints, respectively. Patients are upfront randomized for the two induction schedules (Gemtuzumab Ozogamicin (GO)-147 versus GO-1; ratio 1:1) and for Glasdegib or Placebo (double blinded, ratio 1:1) as adjunct to consolidation therapy and as single agent 6 months maintenance therapy. Chemotherapy backbone for induction therapy is standard 7+3 with cytarabine 200mg/m² continuously day 1 to day 7, daunorubicin 60mg/m² days 1, 2 and 3 and for consolidation therapy intermediate dose cytarabine (1g/m², bi-daily, days 1,2,3). The trial is designed to gain evidence of anti-leukemic activity of GO and Glasdegib in older patients with newly diagnosed acute myeloid leukemia.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Gemtuzumab Ozogamicin 147, Gemtuzumab Ozogamicin 1, Glasdegib, Placebo Oral Tablet
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gemtuzumab Ozogamicin 147Drug
Also called GO147
Induction therapy: Gemtuzumab Ozogamicin 3mg/m² on days 1,4 and 7
Gemtuzumab Ozogamicin 1Drug
Also called GO1
Induction therapy: Gemtuzumab Ozogamicin 3mg/m² on day 1
GlasdegibDrug
Also called _G
Consolidation \& Maintenance therapy Glasdegib 100mg on days 4 to 27
Placebo Oral TabletDrug
Also called _P
Consolidation \& Maintenance therapy Placebo 100mg on days 4 to 27
| Study group | Role | What they receive |
|---|---|---|
| GO147_G | Experimental | GO147: Induction therapy: Gemtuzumab Ozogamicin 3mg/m² on days 1,4 and 7
_G: Consolidation \& Maintenance therapy Glasdegib 100mg on days 4 to 27 Receives: Drug: Gemtuzumab Ozogamicin 147; Drug: Glasdegib |
| GO147_P | Placebo comparator | GO147: Induction therapy: Gemtuzumab Ozogamicin 3mg/m² on days 1,4 and 7
_P: Consolidation \& Maintenance therapy Placebo 100mg on days 4 to 27 Receives: Drug: Gemtuzumab Ozogamicin 147; Drug: Placebo Oral Tablet |
| GO1_G | Experimental | GO1: Induction therapy: Gemtuzumab Ozogamicin 3mg/m² on day 1
_G: Consolidation \& Maintenance therapy Glasdegib 100mg on days 4 to 27 Receives: Drug: Gemtuzumab Ozogamicin 1; Drug: Glasdegib |
| GO1_P | Placebo comparator | GO1: Induction therapy: Gemtuzumab Ozogamicin 3mg/m² on day 1
_P: Consolidation \& Maintenance therapy Placebo 100mg on days 4 to 27 Receives: Drug: Gemtuzumab Ozogamicin 1; Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRD-negativity
Minimal Residual Disease negativity (MRD-negativity) after induction therapy measured by flow cytometry.
Measured: Collected during the first MRD-analysis after the first induction therapy cycle (after 4 weeks)
Secondary outcomes (1)
EFS
Event-free survival
Measured: Collected after 2 years follow-up time
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2019
- Study start1 Apr 2021
- Primary completion15 Jun 2022
- Study completion23 Jun 2022
Why it stopped: Study turned out no longer feasible. End of Recruitment: 25.5.2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- The two research questions are addressed in a 2 by 2 factorial design. Patients are upfront randomized for the two induction schedules (GO-147 versus GO-1, ratio 1:1) and for Glasdegib or Placebo (double blinded, ratio 1:1) as adjunct to consolidation therapy and as single agent 6 months maintenance therapy.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Heidelberg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Dr. Richard F Schlenk, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04093505
- Sponsor's protocol ID
- NCT-2017-0537
- Acronym
- GnG
- Status last verified
- Jun 2022
- First submitted
- 30 Oct 2018
- Last updated
- 1 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jaramillo S, Krisam J, Le Cornet L, Kratzmann M, Baumann L, Sauer T, Crysandt M, Rank A, Behringer D, Teichmann L, Gorner M, Trappe RU, Rollig C, Krause S, Hanoun M, Hopfer O, Held G, Buske S, Fransecky L, Kayser S, Schliemann C, Schaefer-Eckart K, Al-Fareh Y, Schubert J, Geer T, Kaufmann M, Brecht A, Niemann D, Kieser M, Bornhauser M, Platzbecker U, Serve H, Baldus CD, Muller-Tidow C, Schlenk RF. Rationale and design of the 2 by 2 factorial design GnG-trial: a randomized phase-III study to compare two schedules of gemtuzumab ozogamicin as adjunct to intensive induction therapy and to compare double-blinded intensive postremission therapy with or without glasdegib in older patients with newly diagnosed AML. Trials. 2021 Nov 3;22(1):765. doi: 10.1186/s13063-021-05703-w.
PubMed 34732236
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase-III Study to Compare Two Schedules of Gemtuzumab Ozogamicin as Adjunct to Intensive Induction Therapy and to Compare Intensive Postremission Therapy Double Blinded With or Without Glasdegib in Older Patients With Newly Diagnosed AML
- ClinicalTrials.gov ID
- NCT04093505
- Acronym / sponsor ID
- GnG / NCT-2017-0537
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study turned out no longer feasible. End of Recruitment: 25.5.2022
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University Hospital HeidelbergUniversity, hospital or other
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 15 Jun 2022 (actual)
- Study completion
- 23 Jun 2022 (actual)
- First posted
- 18 Sep 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 study is a randomized phase III trial with a 2x2 factorial design with measurable residual disease and event-free survival as primary endpoints, respectively. Patients are upfront randomized for the two induction schedules (Gemtuzumab Ozogamicin (GO)-147 versus GO-1; ratio 1:1) and for Glasdegib or Placebo (double blinded, ratio 1:1) as adjunct to consolidation therapy and as single agent 6 months maintenance therapy. Chemotherapy backbone for induction therapy is standard 7+3 with cytarabine 200mg/m² continuously day 1 to day 7, daunorubicin 60mg/m² days 1, 2 and 3 and for consolidation therapy intermediate dose cytarabine (1g/m², bi-daily, days 1,2,3). The trial is designed to gain evidence of anti-leukemic activity of GO and Glasdegib in older patients with newly diagnosed acute myeloid leukemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- The two research questions are addressed in a 2 by 2 factorial design. Patients are upfront randomized for the two induction schedules (GO-147 versus GO-1, ratio 1:1) and for Glasdegib or Placebo (double blinded, ratio 1:1) as adjunct to consolidation therapy and as single agent 6 months maintenance therapy.
| Arm | Type | Receives |
|---|---|---|
| GO147_G | Experimental | Drug: Gemtuzumab Ozogamicin 147, Drug: GlasdegibGO147: Induction therapy: Gemtuzumab Ozogamicin 3mg/m² on days 1,4 and 7 _G: Consolidation \& Maintenance therapy Glasdegib 100mg on days 4 to 27 |
| GO147_P | Placebo comparator | Drug: Gemtuzumab Ozogamicin 147, Drug: Placebo Oral TabletGO147: Induction therapy: Gemtuzumab Ozogamicin 3mg/m² on days 1,4 and 7 _P: Consolidation \& Maintenance therapy Placebo 100mg on days 4 to 27 |
| GO1_G | Experimental | Drug: Gemtuzumab Ozogamicin 1, Drug: GlasdegibGO1: Induction therapy: Gemtuzumab Ozogamicin 3mg/m² on day 1 _G: Consolidation \& Maintenance therapy Glasdegib 100mg on days 4 to 27 |
| GO1_P | Placebo comparator | Drug: Gemtuzumab Ozogamicin 1, Drug: Placebo Oral TabletGO1: Induction therapy: Gemtuzumab Ozogamicin 3mg/m² on day 1 _P: Consolidation \& Maintenance therapy Placebo 100mg on days 4 to 27 |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients with newly diagnosed acute myeloid leukemia according to the 2016 WHO classification
- Genetic and immunophenotypic assessment in one of the central laboratories
- No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis (≤ 7 days)
- Age ≥ 60 years, no upper age limit
- ECOG performance status (ECOG PS) ≤ 2. See appendix 18.1
Key exclusion criteria (19 listed)
- AML with PML-RARA or BCR-ABL1
- Patients with known active central nervous system leukemia (assessed clinically).
- Prior treatment with a smoothened inhibitor (SMOi) and/or hypomethylating agent for AML. (Treatment of a preceding MDS (myelodysplastic syndrome) with HMA is not an exclusion criterion.)
- Inadequate renal function: creatinine > 1.5 x upper normal serum level; estimated creatinine clearance ≤30 ml/min (calculated using the standard method for the institution).
- Inadequate liver function: ALT and AST ≥ 2.5 x ULN), total bilirubin ≥ 1.5 x ULN; Alkaline phosphatase ≥ 2.5 x ULN. Known liver cirrhosis or history of veno-occlusive disease (VOD) or history of Sinusoidal Obstruction Syndrome (SOS)
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 |
|---|---|---|
| Gemtuzumab Ozogamicin 147Also: GO147Induction therapy: Gemtuzumab Ozogamicin 3mg/m² on days 1,4 and 7 | Drug | GO147_G, GO147_P |
| Gemtuzumab Ozogamicin 1Also: GO1Induction therapy: Gemtuzumab Ozogamicin 3mg/m² on day 1 | Drug | GO1_G, GO1_P |
| GlasdegibAlso: _GConsolidation \& Maintenance therapy Glasdegib 100mg on days 4 to 27 | Drug | GO147_G, GO1_G |
| Placebo Oral TabletAlso: _PConsolidation \& Maintenance therapy Placebo 100mg on days 4 to 27 | Drug | GO147_P, GO1_P |
Primary outcome
MRD-negativity
Time frame: Collected during the first MRD-analysis after the first induction therapy cycle (after 4 weeks)
Minimal Residual Disease negativity (MRD-negativity) after induction therapy measured by flow cytometry.
1 secondary outcome
EFS
Time frame: Collected after 2 years follow-up time
Results and safety
The study was stopped early (reason given: Study turned out no longer feasible. End of Recruitment: 25.5.2022). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2022.
- Derived from this study: PubMed 34732236Jaramillo S, Krisam J, Le Cornet L, Kratzmann M, Baumann L, Sauer T, Crysandt M, Rank A, Behringer D, Teichmann L, Gorner M, Trappe RU, Rollig C, Krause S, Hanoun M, Hopfer O, Held G, Buske S, Fransecky L, Kayser S, Schliemann C, Schaefer-Eckart K, Al-Fareh Y, Schubert J, Geer T, Kaufmann M, Brecht A, Niemann D, Kieser M, Bornhauser M, Platzbecker U, Serve H, Baldus CD, Muller-Tidow C, Schlenk RF. Rationale and design of the 2 by 2 factorial design GnG-trial: a randomized phase-III study to compare two schedules of gemtuzumab ozogamicin as adjunct to intensive induction therapy and to compare double-blinded intensive postremission therapy with or without glasdegib in older patients with newly diagnosed AML. Trials. 2021 Nov 3;22(1):765. doi: 10.1186/s13063-021-05703-w.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Gemtuzumab Ozogamicin 147, Gemtuzumab Ozogamicin 1 and Glasdegib 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 12 inclusion and 19 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: stopped early, as of the sponsor's last update on 1 Jul 2022. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 was stopped early (reason given: Study turned out no longer feasible. End of Recruitment: 25.5.2022). Results are not available in the source record.
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?
MRD-negativity (time frame: Collected during the first MRD-analysis after the first induction therapy cycle (after 4 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04093505, which also lists 1 linked publication.
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 1 Jul 2022.