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

NCT03207191 | Completed Phase 1 DMC

• 1 other identifier: PH-F16IL2CD33-03/15
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Acute Myeloid Leukemia (AML) Relapse

Outcome Measures

Primary Outcomes (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

  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)

• Overall response rate (ORR)

  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

• Relapse-free survival (RFS)

  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

• Time to response (CR or CRi) of responding patients

  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

• Overall survival (OS) rate

  From day 1 up to week 76, every 4 weeks

• Rate to complete donor chimerism

  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

Study Arms (1)

F16IL2 + BI 836858

EXPERIMENTAL

Successive 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.

Drug: F16IL2; Drug: BI 836858

Interventions

F16IL2 DRUG

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

F16IL2 + BI 836858

BI 836858 DRUG

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

F16IL2 + BI 836858

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Philogen S.p.A.: lead
• Boehringer Ingelheim: collaborator

Study Sites (2)

University Medical Center Freiburg

Freiburg im Breisgau, Germany

Location

Münster University Hospital

Münster, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

BI 836858

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2016
• First Posted: July 2, 2017
• Study Start: December 2, 2016
• Primary Completion: March 26, 2020
• Study Completion: March 26, 2020
• Last Updated: April 20, 2022

Record last verified: 2022-04

Locations

DE (2)