SL-401 as Consolidation Therapy in Patients With Adverse Risk Acute Myeloid Leukemia in First Complete Remission

NCT02270463 | Terminated Phase 1 Results DMC

• 1 other identifier: STML-401-0214
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 7

Brief Summary

This is a non-randomized, open-label, multicenter, dose escalation study designed to determine the maximum tolerated dose (MTD) of SL-401 in adult patients with acute myeloid leukemia, and to evaluate the safety profile of SL-401 at the MTD.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Dose-Limiting Toxicity (DLT)

  The maximum tolerated dose was defined as the dose preceding the dose level at which 2 or more patients experienced a DLT during treatment Cycle 1.

  24 weeks

Secondary Outcomes (3)

• Eradication of Minimal Residual Disease (MRD) From Baseline

  24 weeks

• Overall Survival (OS)

  Day 1 (enrollment) through Month 44

• Relapse-Free Survival (RFS)

  24 weeks

Study Arms (1)

Tagraxofusp-erzs

EXPERIMENTAL

Patients received tagraxofusp-erzs (SL-401) by IV infusion over 15 minutes for 5 consecutive days of a 28-day cycle in both stages.

Drug: Tagraxofusp-erzs

Interventions

Tagraxofusp-erzs DRUG

Tagraxofusp-Erzs administered by IV infusion at doses of 7, 9, and 12 µg/kg/day

Also known as: SL-401

Tagraxofusp-erzs

Eligibility Criteria

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

You may qualify if:

• The patient has a diagnosis of AML according to World Health Organization (WHO) criteria.
• The patient received any induction chemotherapy regimen and may have received post-remission consolidation therapy prior to screening.
• The patient has achieved a first or second CR or CRi. For patients without evidence of MRD in CR/CRi, CR (or CRi) must have been initially identified within 12 months prior to screening.
• OR The patient has achieved first or second CR or CRi with evidence of MRD as determined locally at least 6 months post stem cell transplant without evidence of acute or chronic graft-versus-host disease post-transplant and has not received immunosuppressant therapy for at least 14 days prior to SL-401 therapy.
• The patient has adverse risk disease or AML for which there is otherwise a substantial risk of relapse, which includes but is not limited to: adverse karyotype, FLT3 internal tandem duplication (ITD) mutation, history of antecedent hematologic disorder (AHD), therapy-related AML, history of requiring more than 1 cycle of intensive induction chemotherapy to achieve first remission, and/or presence of persistent MRD (detected by cytogenetics, molecular markers, or flow cytometry) at any point after the initial induction cycle.
• For patients enrolling in Stage 2, the bone marrow evaluation determined locally within the previous 6 months indicates the presence of MRD.
• The patient is not considered to be an immediate candidate for allogeneic stem cell transplant as determined by the investigator.
• The patient is ≥18 years old.
• The patient has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0-2.
• The patient has adequate organ function, including cardiac, renal, and hepatic function:
• Left ventricular ejection fraction (LVEF) ≥institutional lower limit of normal as measured by multigated acquisition scan (MUGA) or 2-dimensional (2-D) echocardiography (ECHO) within 28 days prior to start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram (ECG)
• Serum creatinine ≤1.5 mg/dL
• Serum albumin ≥3.2 g/dL in the absence of receipt of (IV) albumin within the previous 72 hours.
• Bilirubin ≤1.5 mg/dL
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × the upper limit of normal (ULN)

You may not qualify if:

• The patient has a diagnosis of AML associated with karyotype t(15;17).
• The patient received treatment with another investigational agent within 14 days of screening.
• The patient previously received treatment with SL-401.
• The patient has an active malignancy and/or cancer history (excluding AML or antecedent myelodysplastic syndrome \[MDS\]) that may confound the assessment of the study endpoints. Patients with a past cancer history (within 2 years of entry) with substantial potential for recurrence and/or ongoing active malignancy must be discussed with the Sponsor before study entry. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ, cervical intraepithelial neoplasia, organ-confined prostate cancer with no evidence of progressive disease.
• The patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association \[NYHA\] Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
• The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study.
• The patient has known active or suspected central nervous system (CNS) leukemia. If suspected, CNS leukemia should be ruled out with relevant imaging and/or examination of cerebrospinal fluid.
• The patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation (DIC), or psychiatric illness/social situations that would limit compliance with study requirements.
• The patient is pregnant or breast feeding.
• The patient has known positive status for human immunodeficiency virus (HIV), active or chronic Hepatitis B or Hepatitis C.
• The patient is oxygen-dependent.
• The patient has any medical condition which in the opinion of the Investigator places the patient at an unacceptably high risk for toxicities.

Sponsors & Collaborators

• Stemline Therapeutics, Inc.: lead

Study Sites (7)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 12902, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Institute

Seattle, Washington, 98101, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

tagraxofusp

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

The small number of patients treated at 12 µg/kg/day precluded definitive interpretation of the efficacy data from this study.

Results Point of Contact

• Title: Ira Gupta, MD, Senior Vice President, Clinical Development & Medical Affairs - Hematology
• Organization: Stemline Therapeutics, Inc.

clinicaltrials@menarinistemline.com

1-877-332-7967

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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 9, 2014
• First Posted: October 21, 2014
• Study Start: February 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: October 17, 2024
• Results First Posted: August 21, 2024

Record last verified: 2024-10

Locations

US (7)