LCL161 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis

NCT02098161 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 2013-0612NCI-2014-01241CLCL161AUS02T
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well second mitochondrial-derived activator of caspases (SMAC) mimetic LCL161 (LCL161) works in treating patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytosis myelofibrosis. SMAC mimetic LCL161 may help control the growth of abnormal cells by promoting apoptosis (programmed cell death).

Conditions

Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase; Primary Myelofibrosis; Secondary Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Response

  Will be defined as complete remission (CR), partial remission (PR), or clinical improvement (CI) after 3 courses of treatment according to International Working Group (IWG) consensus criteria for myelofibrosis. Complete remission (CR): bone marrow blasts \<5%, hemoglobin \>/= 10, absolute neutrophil count (ANC) \>/= 1000, platelets \>/= 100, \<2% immature myeloid cell, spleen and liver not palpable. Partial Response (PR): CR plus one or more of the following: ANC \>/= 1000, decreased platelets by 50%, hemoglobin \>/= 8.5 but \< 10, \<2% immature myeloid cells. Clinical improvement (CI): hemoglobin increase of 2g/dl, transfusion independence or reduction splenomegaly and/or hepatomegaly \>/= 50%, \>/=50% reduction in MPN-SAF TSS

  After 3 courses of Therapy

Secondary Outcomes (3)

• Duration of Response

  Up to 7 years 5 Months

• Time to Response

  Up to 7 years 5 months

• Overall Survival

  Up to 7 years 5 months

Study Arms (1)

Treatment (SMAC mimetic LCL161)

EXPERIMENTAL

Patients receive SMAC mimetic LCL161 PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration; Drug: Smac Mimetic LCL161

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (SMAC mimetic LCL161)

Questionnaire Administration OTHER

Ancillary studies

Treatment (SMAC mimetic LCL161)

Smac Mimetic LCL161 DRUG

Given PO

Also known as: LCL161

Treatment (SMAC mimetic LCL161)

Eligibility Criteria

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

You may qualify if:

• Patients must provide written informed consent
• Willing and able to comply with scheduled visits, treatment plan and laboratory tests
• Patient is able to swallow and retain oral medication
• Must be diagnosed with treatment requiring PMF or post ET/PV MF with intermediate-1, intermediate -2 or high risk disease according to the International Working Group (IWG) prognostic scoring system, or if with low risk disease then with symptomatic splenomegaly that is \>= 5 cm below left costal margin by physical exam
• Patients who are not candidates for, intolerant, or relapsed/refractory to ruxolitinib
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) \>= 0.5 x 10\^9/L (1500/mm\^3)
• Serum direct bilirubin =\< 2.0 x ULN (upper limit of normal)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN, except for patients with MF involvement of the liver who must have AST and ALT =\< 5 x ULN
• Serum creatinine =\< 1.5 x ULN
• Treatment-related toxicities from prior therapies must have resolved to grade =\< 1
• At least 2 weeks from prior MF-directed treatment (till the start of study drug)

You may not qualify if:

• Any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while in the study or that could confound discrimination between disease- and study treatment-related toxicities
• Patients who are currently receiving chronic (\> 14 days) treatment with corticosteroids at a dose \>= 10 mg of prednisone (or its glucocorticoid equivalent) per day, or any other chronic immunosuppressive treatment that cannot be discontinued prior to starting study drug
• Patients who are currently receiving treatment with agents that are metabolized solely through cytochrome P450 family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) and have a narrow therapeutic index or are strong cytochrome P450 family 3, subfamily C, polypeptide 8 (CYP2C8) inhibitors; or are receiving treatment with agents that carry a risk for QT prolongation and are CYP3A substrates
• Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LCL161 as per physicians opinion
• Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive beta-human chorionic gonadotropin (HCG) laboratory test
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 90 days after study treatment; highly effective contraception methods include: total abstinence or male partner or female sterilization or combination of any two of the following (a+b or a+c, or b+c): a) use of oral, injected or implanted hormonal methods of contraception, b) placement of an intrauterine device (IUD) or intrauterine system (IUS), c) barrier methods of contraception: condom for male partner or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
• Note: postmenopausal women are allowed to participate in this study; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, a woman is considered to be of not child bearing potential only when her reproductive status has been confirmed by follow-up hormone level assessment
• Sexually active males must use a condom during intercourse while taking the drug and for 3 months after stopping study drug and should not father a child in this period; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Pemmaraju N, Carter BZ, Bose P, Jain N, Kadia TM, Garcia-Manero G, Bueso-Ramos CE, DiNardo CD, Bledsoe S, Daver NG, Popat U, Konopleva MY, Zhou L, Pierce S, Estrov ZE, Borthakur GM, Ohanian M, Qiao W, Masarova L, Wang X, Mak PY, Cortes J, Jabbour E, Verstovsek S. Final results of a phase 2 clinical trial of LCL161, an oral SMAC mimetic for patients with myelofibrosis. Blood Adv. 2021 Aug 24;5(16):3163-3173. doi: 10.1182/bloodadvances.2020003829.

  PMID: 34424319 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Polycythemia Vera; Primary Myelofibrosis

Interventions

LCL161

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders

Results Point of Contact

• Title: Naveen Pemmaraju MD/ Associate Professor
• Organization: The University of Texas MD Anderson Cancer Center

NPemmaraju@mdanderson.org

713-792-4956

Study Officials

• Naveen Pemmaraju

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2014
• First Posted: March 27, 2014
• Study Start: December 18, 2014
• Primary Completion: May 19, 2022
• Study Completion: May 19, 2022
• Last Updated: June 6, 2023
• Results First Posted: June 6, 2023

Record last verified: 2023-05

Locations

US (1)