Tagraxofusp (SL-401) in Patients With CMML or MF

Sponsor

Stemline Therapeutics, Inc. (Other)

Overall Status

Recruiting

CT.gov ID

NCT02268253

Collaborator

(none)

130

Enrollment

Locations

Arm

103

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This multi-center, multi-arm trial is evaluating the safety and efficacy of tagraxofusp, a CD123-targeted therapy, in patients with either chronic myelomonocytic leukemia (CMML) or myelofibrosis (MF). There are two CMML cohorts, one enrolling patients with CMML (CMML-1 or CMML-2) who are refractory/resistant or intolerant to hypomethylating agents (HMA), hydroxyurea (HU), or intensive chemotherapy; and one enrolling treatment-naive patients with CMML (CMML-1 or CMML-2) with molecular features associated with poor prognosis. The MF cohort will enroll patients who are resistant/refractory or intolerant to approved JAK therapy (JAK1/JAK2 or JAK2).

Condition or Disease	Intervention/Treatment	Phase
Myelofibrosis Chronic Myelomonocytic Leukemia	Drug: SL-401	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

130 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Tagraxofusp (SL-401) in Patients With Chronic Myelomonocytic Leukemia (CMML) or Myelofibrosis (MF). [Prior Title: SL-401 in Patients With Advanced, High Risk Myeloproliferative Neoplasms (Systemic Mastocytosis, Advanced Symptomatic Primary Eosinophilic Disorder, Myelofibrosis, Chronic Myelomonocytic Leukemia).]

Actual Study Start Date :

Dec 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tagraxofusp (SL-401)	Drug: SL-401 Other Names: tagraxofusp-erzs

Arm

Intervention/Treatment

Experimental: Tagraxofusp (SL-401)

Drug: SL-401

Other Names:

tagraxofusp-erzs

Outcome Measures

Primary Outcome Measures

Rate and severity of treatment-emergent adverse events [Through 30 days post last dose of tagraxofusp]
Characterize the safety profile of tagraxofusp in patients with CMML and MF by assessing rates of adverse events
Evaluation of rate of response [Through 12 months post last dose of tagraxofusp]
Evaluate the efficacy of tagraxofusp as measured by the rate (%) of response

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Abbreviated Inclusion Criteria:

All Patients (Stages 2 and 3A):

The patient is ≥18 years old.
The patient has a life expectancy of >6 months.
The patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.
The patient has adequate baseline 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) echocardiogram (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 (or ≥32 g/L) 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 times the upper limit of normal (ULN)
Creatine phosphokinase (CPK) ≤2.5 times the ULN
Absolute neutrophil count (ANC) ≥0.5 × 10⁹/L

Additional Abbreviated Inclusion Criteria Specific to Patients with MF (Stage 2):

Patient meets the 2016 WHO diagnostic criteria for MF and has an IPSS/DIPSS/DIPSS-plus intermediate-2 or high-risk disease. Patients with IPSS/DIPSS/DIPSS-plus low or intermediate-1 risk disease who have at least one of the following symptoms are also eligible: MF-related anemia (Hb <10 g/dL), splenomegaly (palpable size >10 cm), leukocytosis (WBC >25 × 10⁹/L), marked thrombocytosis (platelet count >1000 × 10⁹/L), or constitutional symptoms (weight loss >10%, during prior 6 months or fever [>37.5ºC or drenching night sweats for >6 weeks]), as recommended by the ELN/IWG 2018 criteria.
Patient is approved JAK therapy (JAK1/JAK2 or JAK2) resistant/refractory or intolerant, in accordance with the ELN/IWG 2018 criteria, and at least 4 weeks have elapsed between the last dose of any MF-directed drug treatments; excluding HU, and study enrollment (first dose). HU can be continued until 2 weeks prior to study enrollment.
Patient is not eligible for an immediate allo-SCT.

Additional Abbreviated Inclusion Criteria Specific to Patients with CMML (Stage 3A):

Patient has a 2016 WHO-defined diagnosis of CMML (persistent monocytosis ≥1 × 10⁹/L for at least 3 months, with other causes excluded, and monocytes ≥10% of WBC in peripheral blood, no criteria and no previous history of CML, ET, PV, and acute promyelocytic leukemia; if eosinophilic, neither PDGFRA, PDGFRB, FGFR1 rearrangements nor PCM1-JAK2 translocation; <20% blasts in peripheral blood and bone marrow aspirate;

1 following criteria - dysplasia in >1 myeloid lineage, acquired clonal cytogenetic or molecular abnormality in hematopoietic cells).

Patient has 2016 WHO-defined CMML-1 (2-4% blasts in peripheral blood and/or 5-9% blasts in bone marrow) and CMML-2 (5-19% blasts in peripheral blood and/or 10-19% blasts in bone marrow, and/or presence of Auer rods).
Patient is refractory/resistant/intolerant to HMAs, or HU, or intensive chemotherapy OR patient is classified as high-risk based on the presence of morphological features, as described by the 2016 WHO prognostic system, and the clinical and molecular features described in molecularly-integrated prognostic systems, such as the GFM, MMM, and the CMML specific prognostic model (CPSS-Mol), and thus is not expected to benefit from HMAs.
Patient is ineligible for an immediate allo-SCT.

Abbreviated Exclusion Criteria:

All Patients (Stages 2 and 3A):

Persistent clinically significant toxicities Grade ≥2 from previous therapies not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue).
Treatment with any disease-related therapy, including radiation therapy or investigational agent, within 14 days of study entry.
Allogeneic SCT within 3 months of study entry.
Previous treatment with tagraxofusp or known hypersensitivity to any components of the drug product.
Active malignancy and/or cancer history (excluding myeloproliferative disorders and concomitant myeloid malignancies as specified in the inclusion criteria) that can confound the assessment of the study endpoints. Patients with a past cancer history (within 2 years of entry) and/or ongoing active malignancy or substantial potential for recurrence must be discussed with the Sponsor before study entry. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including superficial bladder cancer), cervical intraepithelial neoplasia, or organ-confined prostate cancer with no evidence of progressive disease.
Clinically significant cardiovascular disease, pulmonary disease, or known active or suspected disease involvement of the central nervous system (CNS).
Receiving immunosuppressive therapy, with the exception of corticosteroids as specified in the inclusion criteria and tacrolimus, for treatment or prophylaxis of graft-versus-host disease (GVHD).
Uncontrolled intercurrent illness.
Patient is pregnant or breast feeding.
Patient has known human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C.
Patient is oxygen-dependent.

Additional Exclusion Criteria Specific to Patients with MF and CMML (Stages 2 and 3A) apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	University of California, Los Angeles	Los Angeles	California	United States	90095
3	University of Kansas Cancer Center	Westwood	Kansas	United States	66205
4	Norton Cancer Institute	Louisville	Kentucky	United States	40207
5	Mayo Clinic	Rochester	Minnesota	United States	55905
6	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
7	Weill Cornell Medical Center	New York	New York	United States	10021
8	MD Anderson Cancer Center	Houston	Texas	United States	77030
9	University of Alberta	Edmonton	Alberta	Canada	T6G 2G3
10	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9