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

NCT02957032 | Terminated Phase 1

• 1 other identifier: PH-F16IL2CYT-03/14
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Acute Myeloid Leukemia, Relapsed, Adult

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (10)

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

  Up to 13 months

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

  Up to 12 months

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

  Up to 13 months

• Median progression free survival (PFS)

  Up to 13 months

• Median overall survival (OS)

  Up to 13 months

Study Arms (1)

F16IL2 + cytarabine

EXPERIMENTAL

Patients will be enrolled sequentially in cohorts and treated at different dose levels of F16IL2 and a fixed dose of cytarabine.

Drug: F16IL2; Drug: cytarabine

Interventions

F16IL2 DRUG

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.

F16IL2 + cytarabine

cytarabine DRUG

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.

F16IL2 + cytarabine

Eligibility Criteria

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

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (1)

Münster University Hospital

Münster, 48149, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

Cytarabine

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

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: October 17, 2016
• First Posted: November 7, 2016
• Study Start: April 13, 2016
• Primary Completion: September 29, 2023
• Study Completion: September 29, 2023
• Last Updated: October 10, 2023

Record last verified: 2023-10

Locations

DE (1)