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Acute Myeloid Leukemia (AML) RelapsePhase 1PHIBINCT03207191

Trial to Find and Investigate a Safe Dose of F16IL2 and BI 836858 in Patients With AML Relapse After Allogeneic Hematopoietic Stem Cell Transplantation

A Phase 1 study testing F16IL2 and BI 836858 in people with Acute Myeloid Leukemia (AML) Relapse, run by Philogen S.p.A. at 2 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Phase I, open label, single arm, non-randomized, multicenter, prospective dose escalation study 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 to 75 years
Conditions the study is for
Acute Myeloid Leukemia (AML) Relapse
What is being tested?
F16IL2 and BI 836858
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
2 sitesGermany
Study dates
2 Dec 2016to 26 Mar 2020
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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with de novo or secondary AML according to the WHO/FAB classification relapsing after alloHSCT, and fulfilling at least one of the following:
  • bone marrow blasts ≥ 5% of all nucleated cells
  • appearance of blasts in the peripheral blood
  • extramedullary AML relapse
  • Age 18 - 75 years.
  • ECOG ≤ 2.
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  • Documented negative test for 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, vasectomized 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 sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy)

Who cannot join

  • Known central nervous system manifestation of AML.
  • Previous treatment (e.g., stem cell transplantation, chemotherapy, radiotherapy, investigational drugs) within 4 weeks or a minimum of 5 half-lifes of the treatment, whatever is shorter, of the first study drug intake for this current AML relapse after alloHSCT, except hydroxyurea to control peripheral cell counts up to one day before study medication.
  • Active GvHD requiring systemic immunosuppression, unless controlled with low dose steroids equivalent to a maximum of 10 mg methylprednisolone per day.
  • Chronically impaired renal function (estimated creatinine clearance < 30 ml/min).
  • Inadequate liver function (ALT, AST, ALP or total bilirubin ≥ 3.0 x ULN), if not caused by leukemic infiltration.
  • Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol.
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  • 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.
  • Uncontrolled hypertension.
  • Ischemic peripheral vascular disease (Grade IIb-IV).
  • Severe diabetic retinopathy such as severe non-proliferative retinopathy and proliferative retinopathy.
  • Major trauma including major 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) are allowed.
  • 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).
  • Known hereditary fructose intolerance.
  • 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.
  • Prior treatment with CD33 antibody.
  • Serious, non-healing wound, ulcer or bone fracture.
  • Allergy to study medication or excipients in study medication.
  • Concurrent use of other anti-cancer treatments or agents.
  • Failure to fulfil inclusion criteria.

Trial locations and contacts

2 sites in 1 country.

Germany2 sites

  • University Medical Center Freiburg

    Freiburg im Breisgau

  • Münster University Hospital

    Münster

Other trials in Germany

About this study

Official title: A Phase I Study of the Tumor-targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With the Anti-CD33 Antibody BI 836858 in Patients With AML Relapse After Allogeneic Hematopoietic Stem Cell Transplantation

Phase I, open label, single arm, non-randomized, multicenter, prospective dose escalation study in subjects with acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT).

Read the detailed description

The aim of the study is to determine a recommended dose for F16IL2 in combination with BI 836858 in AML relapse after alloHSCT and investigating safety and tolerability of the combination regimen.

Dose escalation will be guided by a Bayesian logistic regression model (BLRM) with overdose control that will be fitted to binary toxicity outcomes. The estimate of parameters will be updated as data are accumulated using the BLRM. At the end of the dose escalation phase, the probability of toxicity at each dose combination level will be calculated to determine an estimate of the MTD. Once the MTD or a biological active dose has been defined, additional patients (up to 10) will be treated with F16IL2 and BI 836858 dosed at this dose combination in order to confirm the safety profile of the combination.

Being tested
F16IL2, BI 836858
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

    F16IL2 dose escalation with provisional doses of 10, 20 and 30 Mio IU on Day 1, 8, 15 and 22 of each cycle through a rate-controlled intravenous infusion of 3 hours

  • BI 836858Drug

    BI 836858 dose escalation with provisional doses of 10, 20, 40, 80 and 160 mg on days 3, 10, 17 and 24 of each cycle through a rate-controlled intravenous infusion up to 5 hours

Study groups in NCT03207191
Study groupRoleWhat they receive
F16IL2 + BI 836858ExperimentalSuccessive cohorts of patients will receive increasing doses of FI6IL2 and BI 836858 until the MTD is reached. The MTD will be defined following a Bayesian logistic regression model (BLRM) with overdose control. Patients will go off treatment after 6 months (i.e. after 6 cycles of induction combination therapy). Patients achieving CR or CRi will receive maintenance therapy for a maximum of 6 months.
Receives: Drug: F16IL2; Drug: BI 836858

What is being measured

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

  1. Number of patients with adverse events that are related to treatment and classified as DLTs for each administered dosage

    To assess the dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended dose (RD) of F16IL2 combined with BI 836858

    Measured: Safety assessment will be performed from day 1 up to day 28 of the Cycle 1 (each cycle is 28 days) for every patient until the end of the enrollment

Secondary outcomes (26)

  1. Overall response rate (ORR)

    Measured: 1) from week 4 up to week 24, every 4 weeks; 2) for EoT: at week 26 (only induction) or 50 (plus maintenance); 3) for follow-up: from week 28 (only induction) or 52 (plus maintenance) up to week 76, every 4 weeks

  2. Relapse-free survival (RFS)

    Measured: 1) from week 4 up to week 24, every 4 weeks; 2) for EoT: at week 26 (only induction) or 50 (plus maintenance); 3) for follow-up: from week 28 (only induction) or 52 (plus maintenance) up to week 76, every 4 weeks

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

    Measured: 1) from week 4 up to week 24, every 4 weeks; 2) for EoT: at week 26 (only induction) or 50 (plus maintenance); 3) for follow-up: from week 28 (only induction) or 52 (plus maintenance) up to week 76, every 4 weeks

  4. Overall survival (OS) rate

    Measured: From day 1 up to week 76, every 4 weeks

  5. Rate to complete donor chimerism

    Measured: 1) day 0; 2) from week 4 up to week 24, every 4 weeks; 3) for EoT: at week 26 (only induction) or 50 (plus maintenance); 4) for follow-up: from week 28 (only induction) or 52 (plus maintenance) up to week 76 every 4 weeks

  6. Time to complete donor chimerism

    Measured: 1) day 0; 2) from week 4 up to week 24, every 4 weeks; 3) for EoT: at week 26 (only induction) or 50 (plus maintenance); 4) for follow-up: from week 28 (only induction) or 52 (plus maintenance) up to week 76 every 4 weeks

  7. Maximum drug concentration [Cmax]

    Pharmacokinetics assessment of F16IL2 through blood sampling

    Measured: Cycle 1,1) at day 1,2 (week 1); 2) at day 22,23 (week 4)

  8. Time to reach maximum drug concentration [Tmax]

    Pharmacokinetics assessment of F16IL2 through blood sampling

    Measured: Cycle 1,1) week 1; 2) week 4

  9. Terminal half-life [t1/2]

    Pharmacokinetics assessment of F16IL2 through blood sampling

    Measured: Cycle 1,1) at day 1,2 (week 1); 2) at day 22,23 (week 4)

  10. Area under the drug concentration-time curve [AUC(0 - t last)] and area under the drug concentration-time curve, extrapolated to infinity [AUC]

    Pharmacokinetics assessment of F16IL2 through blood sampling

    Measured: Cycle 1, 1) at day 1,2 (week 1); 2) at day 22,23 (week 4)

  11. Accumulation ratio for AUC [R AUC], Cmax [Rmax] and Cmin [R min]

    Pharmacokinetics assessment of F16IL2 through blood sampling

    Measured: Cycle 1,1) at day 1,2 (week 1); 2) at day 22,23 (week 4)

  12. Total clearance following the dose administered [CL]

    Pharmacokinetics assessment of F16IL2 through blood sampling

    Measured: Cycle 1,1) at day 1,2 (week 1); 2) at day 22,23 (week 4)

  13. Volume of distribution at steady state [Vss]

    Pharmacokinetics assessment of F16IL2 through blood sampling

    Measured: Cycle 1,1) at day 1,2 (week 1); 2) at day 22,23 (week 4)

  14. Mean residence time [MRT]

    Pharmacokinetics assessment of F16IL2 through blood sampling

    Measured: Cycle 1,1) at day 1,2 (week 1); 2) at day 22,23 (week 4)

  15. Maximum drug concentration [Cmax]

    Pharmacokinetics assessment of BI 836858 through blood sampling

    Measured: Cycle 1 [at day 3,4,6 (week 1); at day 24,25,27 (week 4)]

  16. Time to reach maximum drug concentration [Tmax]

    Pharmacokinetics assessment of BI 836858 through blood sampling

    Measured: Cycle 1 [at day 3,4,6 (week 1); at day 24,25,27 (week 4)]

  17. Terminal half-life [t1/2]

    Pharmacokinetics assessment of BI 836858 through blood sampling

    Measured: Cycle 1 [at day 3,4,6 (week 1); at day 24,25,27 (week 4)]

  18. Area under the drug concentration-time curve [AUC(0 - t last)] and area under the drug concentration-time curve, extrapolated to infinity [AUC]

    Pharmacokinetics assessment of BI 836858 through blood sampling

    Measured: Cycle 1 [at day 3,4,6 (week 1); at day 24,25,27 (week 4)]

  19. Accumulation ratio for AUC [R AUC], Cmax [Rmax] and Cmin [R min]

    Pharmacokinetics assessment of BI 836858 through blood sampling

    Measured: Cycle 1 [at day 3,4,6 (week 1); at day 24,25,27 (week 4)]

  20. Total clearance following the dose administered [CL]

    Pharmacokinetics assessment of BI 836858 through blood sampling

    Measured: Cycle 1 [at day 3,4,6 (week 1); at day 24,25,27 (week 4); up to week 21, 22, 23, 24 of Cycle 6, every 4 weeks]

  21. Volume of distribution at steady state [Vss]

    Pharmacokinetics assessment of BI 836858 through blood sampling

    Measured: Cycle 1 [at day 3,4,6 (week 1); at day 24,25,27 (week 4)]

  22. Mean residence time [MRT]

    Pharmacokinetics assessment of BI 836858 through blood sampling

    Measured: Cycle 1 [at day 3,4,6 (week 1); at day 24,25,27 (week 4)]

  23. Human anti-fusion protein antibodies (HAFA) levels

    Measured: 1) at day 1 of every 28 day cycle, from Cycle 1 up to Cycle 12; 2) for EoT: at week 26 (only induction) or 50 (plus maintenance); 3) for follow-up: at week 28 (only induction) or 52 (plus maintenance)

  24. BI 836858 anti-drug antibodies (ADAs) levels

    Measured: From Cycle 1 to Cycle 6, [at day 3 (week 1); at day 10 (week 2); at day 17 (week 3); at day 24 (week 4)]

  25. The rate of acute and chronic GvHD

    Measured: From day 1 up to week 76, every 4 weeks

  26. The severity of acute and chronic GvHD

    Measured: From day 1 up to week 76, every 4 weeks

Timeline

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

  1. First posted2 Jul 2017
  2. Study start2 Dec 2016
  3. Primary completion26 Mar 2020
  4. Study completion26 Mar 2020

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
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03207191
Sponsor's protocol ID
PH-F16IL2CD33-03/15
Acronym
PHIBI
Status last verified
Apr 2022
First submitted
16 Dec 2016
Last updated
20 Apr 2022
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing F16IL2 and BI 836858 in people with Acute Myeloid Leukemia (AML) Relapse, run by Philogen S.p.A. at 2 sites 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 25 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: finished, as of the sponsor's last update on 20 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Number of patients with adverse events that are related to treatment and classified as DLTs for each administered dosage (time frame: Safety assessment will be performed from day 1 up to day 28 of the Cycle 1 (each cycle is 28 days) for every patient until the end of the enrollment). 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 NCT03207191.

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 20 Apr 2022.

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