AzTrials
AzTrials

Acute Myeloid Leukemia, Relapsed, AdultPhase 1NCT02957032

A Study of the Tumor-targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Very Low-dose Cytarabine in Patients With AML Relapse After Allogeneic Hematopoietic Stem Cell Transplantation

A Phase 1 study testing F16IL2 and cytarabine in people with Acute Myeloid Leukemia, Relapsed, Adult, run by Philogen S.p.A. at 1 site in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

Phase I, open label, non-randomized, multicenter, prospective dose escalation study of F16IL2 in combination with very low-dose cytarabine in subjects with acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia, Relapsed, Adult
What is being tested?
F16IL2 and cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteGermany
Study dates
13 Apr 2016to 29 Sep 2023
Phase
Phase 1
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

  • Patients with AML (except APL) relapse after alloHSCT meeting the following criteria (at least one feature must be present):
  • bone marrow blasts ≥ 5% of all nucleated cells
  • appearance of blasts in the peripheral blood
  • extramedullary AML relapse.
  • Age ≥18 years.
  • ECOG ≤ 2.
Show all 12Show fewer
  • Documented negative test HIV-HBV-HCV. For HBV serology: the determination of HBsAg, anti-HBsAg-Ab and anti-HBCAg-Ab is required. In patients with serology documenting previous exposure to HBV (i.e., anti-HBs Ab with no history of vaccination and/or anti-HBc Ab), negative serum HBV-DNA is required.
  • Negative serum pregnancy test for females of childbearing potential* within 14 days of starting treatment.
  • Informed consent, personally signed and dated to participate in the study.
  • Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
  • Women of childbearing potential (WOCBP) must be using, from the screening to six months following the last study drug administration, highly effective contraception methods, as defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group (www.hma.eu/ctfg.html) and which include, for instance, progesteron-only or combined (estrogen- and progesteron-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion, vasectomised partner or sexual abstinence. Pregnancy test will be repeated at the end of treatment visit.
  • Women of childbearing potential are defined as females who have experienced menarche, are not postmenopausal (12 months with no menses without an alternative medical cause) and are not permanently sterilised (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy).

Who cannot join

  • Known central nervous system manifestation of AML.
  • Previous therapy (chemotherapy, radiotherapy, investigational drugs) for this current AML relapse after alloHSCT, unless this previous treatment yielded in a documented progression of the disease and except hydroxyurea to control peripheral cell counts up to 24h before study medication.
  • Active GvHD requiring systemic immunosuppression, unless controlled with low dose steroids equivalent to a maximum of 10 mg methylprednisolone per day.
  • All acute toxic effects of any prior therapy returned to G≤1 according to CTCAE v4.03 (excluding alopecia)
  • Chronically impaired renal function (creatinine clearance < 30 ml/min).
  • Inadequate liver function (ALT, AST, AP or total bilirubin ≥ 3.0 x ULN), if not caused by leukemic infiltration.
Show all 23Show fewer
  • Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol.
  • History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
  • Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).
  • Irreversible cardiac arrhythmias requiring permanent medication.
  • LVEF < 50%
  • Uncontrolled hypertension.
  • Ischemic peripheral vascular disease (Grade IIb-IV). Severe diabetic retinopathy such as severe non-proliferative retinopathy and proliferative retinopathy.
  • Major trauma including surgery (such as abdominal/cardiac/thoracic surgery) within 4 weeks of administration of study treatment.
  • Pregnancy or breast feeding.
  • Requirement of chronic administration of corticosteroids. However, low dose corticosteroids (maximum 10 mg methylprednisolone (or equivalent) per day when administered for GVHD or cancer symptoms (e.g., pain, dyspnoea, lack of appetite).
  • Presence of active and uncontrolled infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
  • Known active or latent tuberculosis (TB).
  • Concurrent malignancies other than AML (except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the patient has been disease-free for at least 2 years.
  • Concomitant treatment with angiogenesis inhibitors or other drugs with proven anti-leukemic activity.
  • Serious, non-healing wound, ulcer or bone fracture.
  • Allergy to study medication or excipients in study medication (not including drug fever or rash to cytarabine).
  • Concurrent use of other anti-cancer treatments or agents with the exception of palliative radiation, e.g. to myelosarcoma lesions not blinding the efficacy judgement of the study treatment.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Münster University Hospital

    Münster, 48149

Other trials in Germany

About this study

Official title: A Dose-finding Phase I Study of the Tumor-targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Very Low-dose Cytarabine in Patients With AML Relapse After Allogeneic Hematopoietic Stem Cell Transplantation

Phase I, open label, non-randomized, multicenter, prospective dose escalation study of F16IL2 in combination with very low-dose cytarabine in subjects with acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT).

Read the detailed description

Phase I, open label, non-randomized, multicenter, prospective dose escalation study of F16IL2 in combination with very low-dose cytarabine in subjects with acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT).

The aim of the study is to determine a recommended dose for F16IL2 in AML relapse after alloHSCT and investigating the toxicity of the combination regimen.

Patients will be enrolled sequentially in cohorts and treated at different dose levels of F16IL2 and a fixed dose of cytarabine. All patients first receive an initial run-in dose of 30 Mio IU of F16IL2 on day 1 and escalating doses of F16IL2 on day 1, 8, 15 and 22. Patients will be treated with cytarabine (5 mg twice daily s.c. for 10 days). The following F16IL2 administration will be at the dose of the respective cohort (days 8, 15 and 22).

The RD will be defined following a traditional 3+3 design. The dose escalation will continue until the MTD is found, that is until at least two patients among a cohort of three to six patients experience a dose limiting toxicity (DLT) (i.e., >33 % of patients with a DLT). The RD is defined as the dose level just below the MTD level. If the MTD is not found at cohort 5 the RD for this study will be considered equal to the cohort 5 dosage.

Being tested
F16IL2, cytarabine
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.

  • F16IL2Drug

    All patients first receive an initial run-in dose of 30 Mio IU of F16IL2 on day 1 and escalating doses of F16IL2 on day 1, 8, 15 and 22.

    Treatment will be repeated every 28 days for up to three cycles.

  • cytarabineDrug

    Patients will be treated with cytarabine (5 mg twice daily s.c. for 10 days). Treatment will be repeated every 28 days for up to three cycles.

Study groups in NCT02957032
Study groupRoleWhat they receive
F16IL2 + cytarabineExperimentalPatients will be enrolled sequentially in cohorts and treated at different dose levels of F16IL2 and a fixed dose of cytarabine.
Receives: Drug: F16IL2; Drug: cytarabine

What is being measured

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

  1. Dose limiting toxicity (DLT)

    To assess the safety, including maximum tolerated dose (MTD), recommended dose (RD) and dose limiting toxicity (DLT) of F16IL2 combined with very low dose cytarabine, Adverse Events (AEs) assessment based on CTCAE v.4.03 will be considered.

    Measured: Safety assessment will be performed from Day 1 up to Day 28 of the Cycle 1 (each cycle is 28 days)

Secondary outcomes (10)

  1. The overall response rate (ORR, consisting of CR and CRi as defined by the International Working Group (IWG) criteria).

    Measured: Up to 13 months

  2. The relapse-free survival (RFS) of responding (CR and CRi) patients.

    Measured: Up to 12 months

  3. The time to response (CR or CRi) of responding patients.

    Measured: Up to 13 months

  4. Median progression free survival (PFS)

    Measured: Up to 13 months

  5. Median overall survival (OS)

    Measured: Up to 13 months

  6. The time to complete donor chimerism.

    Measured: Up to 13 months

  7. The rate to complete donor chimerism.

    Measured: Up to 13 months

  8. The rate of acute GvHD.

    Measured: Up to 13 months

  9. The rate of chronic GvHD.

    The rate of patients with chronic GvHD will be summarized according to the following Chronic GVHD Staging:

    • mild: involvement of 1 to 2 organs/sites (except for lung) with a maximum score of 1;
    • moderate: involvement of at least 1 organ/site with a score of 2 or ≥ 3 organs/sites with a score of 1 or lung involvement with a score of 1;
    • severe: any organ/site with a score of 3 or lung involvement with a score of 2.

    Measured: Up to 13 months

  10. Human anti-fusion protein antibodies (HAFA) levels before and following treatment.

    Measured: at Day 1 (cycle 1), at Day 29 (cycle 2), Day 57 (cycle 3), from Day 25 to Day 85 (EoT visit), from Day 53 to Day 113 (first follow-up visit)

Timeline

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

  1. First posted7 Nov 2016 (estimated)
  2. Study start13 Apr 2016
  3. Primary completion29 Sep 2023
  4. Study completion29 Sep 2023

Why it stopped: New agents for the same indication impacted on patients' recruitment

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02957032
Sponsor's protocol ID
PH-F16IL2CYT-03/14
Status last verified
Oct 2023
First submitted
17 Oct 2016
Last updated
10 Oct 2023
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing F16IL2 and cytarabine in people with Acute Myeloid Leukemia, Relapsed, Adult, run by Philogen S.p.A. 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 23 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 10 Oct 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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: New agents for the same indication impacted on patients' recruitment). 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?

Dose limiting toxicity (DLT) (time frame: Safety assessment will be performed from Day 1 up to Day 28 of the Cycle 1 (each cycle is 28 days)). 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 NCT02957032.

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 10 Oct 2023.

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

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in