- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05063123
Study to Assess an Interphase Cycle With Flotetuzumab. (HOVON162AML)
A Phase II Multicenter Study to Assess the Feasibility and Efficacy of the Addition of an Interphase Cycle With Flotetuzumab Prior to Start Conditioning for an Allogeneic HCT in AML With MRD After 2 Cycles of Intensive Chemotherapy
Study Overview
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
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Amsterdam, Netherlands
- NL-Amsterdam-VUMC
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Groningen, Netherlands
- NL-Groningen-UMCG
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Maastricht, Netherlands
- NL-Maastricht-MUMC
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Rotterdam, Netherlands
- NL-Rotterdam-ERASMUSMC
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥18 years.
- Diagnosis of ELN AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants of these according to the 2016 WHO classification.
- In first CR/CRi/CRh after at at least 2 cycles of intensive chemotherapy with MRD by l MFC-based MRD assay or qPCR mutant NPM1 assessed by central lab. Three cycles of intensive treatment is allowed if 2 cycles of treatment were needed to reach morphological remission.
- Should be off any active systemic therapy for AML for at least 14 days or 5 half-lives (whichever is longer) prior to study registration
- All Grade 2-4 non-hematologic toxicities should have resolved.
- Planned to undergo myeloablative or reduced intensity conditioning prior to alloHCT with a likely source for donor cells identified.
- Eastern Cooperative Oncology Group (ECOG)/ WHO performance status 0-2.
Adequate hepatic and renal function
- Both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (less or equal then) 2.5 times the institutional upper limit of normal (ULN).
- Total bilirubin level (less or equal then) 1.5 times the ULN (unless the patient has a history of Gilbert's Syndrome, in which case, total bilirubin must be (less or equal then) 2.5 times the ULN).
- Serum creatinine level (less or equal then) 1.5 times the ULN or a calculated or measured creatinine clearance of ≥ 50 mL/min.
Adequate organ reserve including cardiovascular, pulmonary, renal, and hepatic functioning sufficient, in the judgment of the Investigator, to undergo therapy.
- If there is a history or signs of heart failure, an echocardiography or MUGA should be obtained, with the estimated left ventricular ejection fraction required to be ≥45%.
- Women of childbearing potential must test negative for pregnancy at enrollment.
- Sexually active women of child-bearing potential must be willing to use a highly effective method of birth control from the time of consent through 12 weeks after flotetuzumab administration. A highly effective method is defined as those which result in a low failure rate (i.e., less than 1% per year) such as implants, injectables, combined oral contraceptives, intra-uterine devices (IUDs) or vasectomized partner.
- Male patients with partners of childbearing potential must be either vasectomized or agree to use a condom in addition to having their partners use another method of contraception resulting in a highly effective method of birth control defined as those which result in a low failure rate (i.e., less than 1% per year) such as implants, injectables, combined oral contraceptives, or IUDs. Patients should not have sexual intercourse with females who are either pregnant or lactating without double barrier contraception. Contraception should be employed from the time of consent through 12 weeks after flotetuzumab administration.
- Patient is able and willing to adhere to the study visit schedule and other protocol requirements.
- Patient is capable of giving informed consent.
- Written informed consent.
Exclusion Criteria:
- Prior history of allogeneic HCT.
- Prior treatment with an anti-CD123-directed agent.
- Favorable risk AML other than AML with NPM1 mutation (according to 2017 ELN)
- Myeloid blast crisis of chronic myeloid leukemia (CML).
- Concomitant illness associated with an estimated survival of <1 year.
- Any active untreated autoimmune disorders (with the exception of vitiligo, resolved childhood atopic dermatitis, prior Grave's disease now euthyroid clinically and with stable supplementation).
Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed. Patients with the following history/concurrent conditions are allowed:
- Basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer
- Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials, and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired [e.g. chronic viral hepatitis, HIV]). Patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24 hours.
- Requirement, at the time of study entry, for concurrent steroids >10 mg/day of oral prednisone or the equivalent, except steroid inhaler, nasal spray or ophthalmic solution.
- Use of immunosuppressant medications (other than steroids as noted) in the 2 weeks prior to study drug administration.
- Use of granulocyte colony stimulating or granulocyte-macrophage colony stimulating factor in the 2 weeks prior to study drug administration.
- Known central nervous system (CNS) leukemia. Patients with suspected CNS leukemia must be evaluated by lumbar puncture and be free of CNS disease prior to study entry. Previously treated CNS leukemia is allowed provided adequate treatment has been provided and the patient is free of CNS disease.
- Known hypersensitivity to murine, yeast, or recombinant proteins; polysorbate 80; recombinant human serum albumin; benzyl alcohol; or any excipient contained in the flotetuzumab drug formulation.
- Dementia or altered mental status that would preclude sufficient understanding to provide informed consent.
- Pregnant or lactating female patient.
- Current participation in another clinical trial.
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Single arm - Flotetuzumab
1 - 3 cycles of Flotetuzumab.
Flotetuzumab will be administered intravenously via continuous (pump) administration.
At least for the first 7 days of cycle 1, the drug will be administered in an inpatient hospital setting, but afterwards may be administered in an outpatient setting using an ambulatory pump configuration.
Flotetuzumab will be dosed using multi-step increments in dosing over the first week as follows: 30, 60, 100, 200, 300, and 400 ng/kg/day each for 24 hours.
On day 7, the dose will be increased to 500 ng/kg/day and administered as a continuous infusion for the remainder of cycle 1.
After 1 cycle of flotetuzumab patients will proceed with alloHCT.
However if there is a delay in access to transplantation, patients are allowed to receive up to 2 additional cycles flotetuzumab provided all non-hematologic toxicities have resolved to Grade <2.
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Flotetuzumab will be given after at least 2 intensive chemotherapy cycles and before the start of the conditioning regimen prior to allo-HCT.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of CR/CRi without MRD defined as MRD < 0.1% by flowcytometry or undetectable mutant NPM1 by qPCR after 1 cycle of flotetuzumab
Time Frame: 1 year after inclusion last patient
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The primary objective of this study is to assess the rate of MRDneg remission after treatment with one cycle of flotetuzumab. The rate of MRDneg remission after one treatment cycle will be tabulated and exact 95% confidence intervals will be calculated. |
1 year after inclusion last patient
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Collaborators and Investigators
Investigators
- Principal Investigator: M. Jongen-Lavrencic, PhD, Erasmus Medical Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- HO162
- 2021-001041-12 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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