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Gemtuzumab Chemotherapy MRD Levels; Glasdegib Post-transplant, Adult Untreated, de Novo, Fav Interm Risk AML

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ClinicalTrials.gov Identifier: NCT04168502
Recruitment Status : Recruiting
First Posted : November 19, 2019
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

Brief Summary:
MRD driven study. Addition of gemtuzumab to conventional chemotherapy to reduce MRD of patients with favorable/intermediate-risk AML. Post-consolidation assessment of MRD. Role of a post-SCT maintenance with glasdegib.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Glasdegib Drug: Gemtuzumab Ozogamicin Phase 3

Detailed Description:
Setting up a multicenter, MRD (Minimal Residual Disease)-driven study that relies on addition of gemtuzumab ozogamicin to conventional chemotherapy to reduce the pre-transplant levels of MRD of patients with favorable/intermediate-risk (according to ELN 2017) AML. Post-consolidation assessment of MRD will be exploited to establish the final risk assignment and to verify whether the delivery of a post remission therapy intensity (AuSCT, Autologous Stem Cell Transplant, vs ASCT, Allogeneic Stem Cell Transplant) of which is MRD-driven will improve the outcome in terms of anti-leukemic efficacy. Finally, the role of a post-SCT maintenance with glasdegib will be explored.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 414 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 3 Study to Assess Gemtuzumab, in Combination With Standard Chemotherapy, on MRD Levels, and the Role of Glasdegib as a Post-transplant Maintenance, in Adult, 18-60 Years, With Previously Untreated de Novo Fav-interm Risk AML
Actual Study Start Date : September 24, 2020
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2027


Arm Intervention/treatment
Experimental: Experimental arm

Induction:

Gemtuzumab 3 mg/m2 day 1,4,7 Daunorubicin 60 mg/m2 day 1-3 Cytosine arabinoside 200 mg/m2 day 1-7

Consolidation:

Gemtuzumab 3 mg/m2 day 1 Daunorubicin 50 mg/m2 day 4-6 Cytosine arabinoside 500 mg/m2 twice a day, day 1-6

Allogeneic transplantation or Autologous transplantation according to MRD level

Maintenance with glasdegib 100 mg daily for one year or until toxicity/relapse

Drug: Glasdegib
After randomization patients in both arms will be randomized to maintenance with glasdegib vs clinical observation

Drug: Gemtuzumab Ozogamicin
Both arms, before randomization, will receive induction and consolidation with Gemtuzumab ozogamicin, Daunorubicin and Cytarabine

Active Comparator: Standard arm

Induction:

Gemtuzumab 3 mg/m2 day 1,4,7 Daunorubicin 60 mg/m2 day 1-3 Cytosine arabinoside 200 mg/m2 day 1-7

Consolidation:

Gemtuzumab 3 mg/m2 day 1 Daunorubicin 50 mg/m2 day 4-6 Cytosine arabinoside 500 mg/m2 twice a day, day 1-6

Allogeneic transplantation or Autologous transplantation according to MRD level

clinical observation

Drug: Gemtuzumab Ozogamicin
Both arms, before randomization, will receive induction and consolidation with Gemtuzumab ozogamicin, Daunorubicin and Cytarabine




Primary Outcome Measures :
  1. Activity of GO in combination with chemotherapy in terms of MRD negativity achievement [ Time Frame: 2 months ]
    Percentage of MRD negativity after consolidation in patients treated in induction and consolidation with GO

  2. Efficacy of Glasdegib maintenance vs clinical observation [ Time Frame: 2,5 years ]
    Disease Free Survival (DFS) in patients randomized to glasdegib maintenance or clinical observation



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed written informed consent according to ICH/EU/GCP and national/local laws
  2. Patients aged between 18 and 60 years
  3. Patients previously untreated for their AML by other chemotherapeutic agents (except for no more than 7 days HU) or radiotherapy
  4. Unequivocal diagnosis of de novo AML according to WHO diagnostic criteria (at least 20% blasts in the bone marrow), other than acute promyelocytic leukemia, documented by bone marrow aspiration (or biopsy in case of dry tap) (not supervening after other myeloproliferative disease or myelodysplastic syndromes of ≥ 6 months duration)
  5. Patients with favorable-intermediate AML according to ELN 2017 (except for FLT3-ITD/TKD positive AML)
  6. WHO performance status 0-3
  7. Adequate renal (serum creatinine ≤ 2 x the institutional ULN) and liver (total serum bilirubin ≤ 2 x ULN; serum ALT and AST ≤ 2.5 x ULN) function, unless considered due to organ leukemic involvement
  8. Left Ventricular Ejection Fraction (LVEF) ≥ 50%, as determined by echocardiogram
  9. Absence of severe concomitant neurological or psychiatric diseases and congestive heart failure or active uncontrolled infection
  10. Absence of any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and the follow-up schedule.

Exclusion Criteria:

  1. Patients already treated for their AML by other chemotherapeutic agents (except for no more than 7 days HU) or radiotherapy
  2. Acute promyelocytic leukemia
  3. Blast crisis of chronic myeloid leukemia
  4. FLT3-ITD/TKD positive AML
  5. AML supervening after other myeloproliferative disease ≥ 6 months duration
  6. AML supervening after antecedent myelodysplastic syndromes
  7. Therapy-related AML
  8. Other active or progressive malignant diseases.
  9. Inadequate renal or liver function (metabolic abnormalities > 2-2.5 times the normal upper limit)
  10. Severe heart failure requiring diuretics
  11. Ejection fraction < 50%
  12. Uncontrolled infections
  13. Severe concomitant neurological or psychiatric diseases
  14. Patients who are pregnant or adults of reproductive potential not employing an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to administration of chemotherapy. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for at least 6 months following discontinuation of study drug.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04168502


Contacts
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Contact: Paola Fazi 0670390528 p.fazi@gimema.it
Contact: Enrico Crea 0670390514 e.crea@gimema.it

Locations
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Italy
A.O. - SS. Antonio e Biagio e Cesare Arrigo - SC Ematologia Recruiting
Alessandria, Italy
Contact: Zallio         
AO "San Giuseppe Moscati" - UOC Ematologia con unità di trapianto Recruiting
Avellino, Italy
Contact: Storti         
AOU Consorziale Policlinico "Aldo Moro" - UO Ematologia con trapianto Recruiting
Bari, Italy
Contact: Carluccio         
Policlinico S. Orsola - Malpighi - UOC Ematologia Recruiting
Bologna, Italy
Contact: Curti         
Presidio Ospedaliero Nord "Santa Maria Goretti" - UOC Ematologia Recruiting
Latina, Italy
Contact: Cimino         
ASL Le/1 P.O. Vito Fazzi - UO Ematologia Recruiting
Lecce, Italy
Contact: Di Renzo         
AOU Policlinico Tor Vergata- UOC Trapianto cellule staminali Recruiting
Roma, Italy
Contact: Adriano Venditti       adriano.venditti@uniroma2.it   
Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
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Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier: NCT04168502    
Other Study ID Numbers: AML1819
First Posted: November 19, 2019    Key Record Dates
Last Update Posted: April 1, 2021
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
De-novo
Favorable risk
Intermediate risk
Gemtuzumab ozogamicin
Glasdegib
Acute Myeloid Leukemia
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Gemtuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents