AzTrials
AzTrials

AMLPhase 2HOVON162AMLNCT05063123

Study to Assess an Interphase Cycle With Flotetuzumab.

A Phase 2 study testing Flotetuzumab in people with AML, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 4 sites in Netherlands.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

Patients who have measurable residual disease (MRDpos, defined as MRD > 0.1% by flowcytometry or detectable mutant Nucleophosmin 1 (NPM1) by quantitative polymerase chain reaction (qPCR) after two cycles of intensive chemotherapy) prior to start conditioning for an allogeneic Hematopoietic Cell Transplantation (HCT)… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
AML
What is being tested?
Flotetuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
4 sitesNetherlands
Study dates
Jan 2022to Dec 2026
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 19Show fewer
  • 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.

Who cannot join

  • 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).
Show all 21Show fewer
  • 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.

Trial locations and contacts

4 sites in 1 country.

Netherlands4 sites

  • NL-Amsterdam-VUMC

    Amsterdam

  • NL-Groningen-UMCG

    Groningen

  • NL-Maastricht-MUMC

    Maastricht

  • NL-Rotterdam-ErasmusMC

    Rotterdam

Other trials in Netherlands

About this study

Official title: 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

Patients who have measurable residual disease (MRDpos, defined as MRD > 0.1% by flowcytometry or detectable mutant Nucleophosmin 1 (NPM1) by quantitative polymerase chain reaction (qPCR) after two cycles of intensive chemotherapy) prior to start conditioning for an allogeneic Hematopoietic Cell Transplantation (HCT) have a very high risk of relapse after transplantation. Important questions in the field are whether patients with MRD after intensive chemotherapy can be converted to MRD negativity (i.e. undetectable MRD, MRDneg) and whether this conversion impacts on the relapse rate after transplantation. This trial aims to develop effective "interphase" treatment for patients in morphological complete remission (CR) with MRD after at least 2 cycles of intensive chemotherapy and prior to start conditioning for an allogeneic HCT. Flotetuzumab, a bispecific antibody-based molecule against CD3 and CD123 in a dual-affinity re-targeting antibody (DART®) format is a new treatment modality based on immunomodulation. The rationale to use flotetuzumab in this study is: 1) its antileukemic activity reported in R/R AML; 2) its limited extra-medullary (i.e. tissue) toxicity; and 3) its short halflife.

Conditions
AML
Being tested
Flotetuzumab
Keywords
MRD positive, APL excluded

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FlotetuzumabDrug

    Flotetuzumab will be given after at least 2 intensive chemotherapy cycles and before the start of the conditioning regimen prior to allo-HCT.

Study groups in NCT05063123
Study groupRoleWhat they receive
Single arm - FlotetuzumabOther1 - 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.
Receives: Drug: Flotetuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of CR/CRi without MRD defined as MRD < 0.1% by flowcytometry or undetectable mutant NPM1 by qPCR after 1 cycle of flotetuzumab

    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.

    Measured: 1 year after inclusion last patient

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Sep 2021
  2. Study startJan 2022 (estimated)
  3. Primary completionAug 2024 (estimated)
  4. Study completionDec 2026 (estimated)

Why it stopped: Withdrawal of MacroGenics (pharmaceutical company)

Resources

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
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05063123
Sponsor's protocol ID
HO162
Other IDs
2021-001041-12
Acronym
HOVON162AML
Status last verified
Sep 2021
First submitted
13 Sep 2021
Last updated
22 Dec 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Data will be shared with Fred Hutchinson / University of Washington Cancer Consortium

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Flotetuzumab in people with AML, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 4 sites in Netherlands.

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 19 inclusion and 21 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: withdrawn, as of the sponsor's last update on 22 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Netherlands. 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 was withdrawn before enrolling participants, so there are no results.

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?

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). 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 NCT05063123.

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 22 Dec 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in