Neoplasms

Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Heart and Blood Diseases

Rare Diseases

Neoplasm Metastasis

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Myeloproliferative Disorders

Bone Marrow Diseases

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Chronic Myeloproliferative Disorders

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.

Laboratory Biomarker Analysis

Questionnaire Administration

Smac Mimetic LCL161

Naveen Pemmaraju

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).

PRIMARY OBJECTIVES:

I. To determine the efficacy of LCL161 as therapy for primary myelofibrosis (PMF), post-polycythemia vera (PV) myelofibrosis (MF) and post-essential thrombocytosis (ET) MF.

II. To determine the objective response which is defined as CR (complete remission) + PR (partial remission) + CI (clinical improvement) after three cycles of treatment.

SECONDARY OBJECTIVES:

I. To determine the safety of LCL161 as therapy for PMF, post-PV MF and post-ET MF.

II. To determine time to response and response duration. III. To assess changes in symptom burden as assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) and M.D. Anderson Symptom Inventory (MDASI) questionnaires.

EXPLORATORY OBJECTIVE:

I. To assess the mechanisms of action of LCL161 in patients with MF; these studies will include the analysis of baculoviral IAP repeat containing 2 (cIAP1), X-linked inhibitor of apoptosis, E3 ubiquitin protein ligase (XIAP), and poly (adenosine diphosphate \[ADP\]-ribose) polymerase 1 (PARP) protein levels which will be determined by western blot (actin as loading control) and will be measured at baseline and at beginning of each cycle for first 3 cycles and at end of study.

OUTLINE:

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

After completion of study treatment, patients are followed up for 30 days.

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

Open Label Phase 2 Single Agent Study of LCL-161 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocytosis Myelofibrosis (Post-ET MF)

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

duration of response is defined as the date at which the subject's objective status is first noted to be a CR or PR to the date progression is documented (if one has occurred) or to the date of last follow-up (for those subjects who have not progressed).

The time to response is defined as the time from study registration to the first date at which the subject's objective status was classified as a response (CR or PR). In subjects who do not achieve a response, time to response will be censored at the subject's last evaluation date. The distribution for each of these event-time variables (duration of response and time to response) will be estimated by Kaplan-Meier curves.

Time from date of treatment start until date of death due to any cause or last Follow-up.

National Cancer Institute (NCI)

Novartis Pharmaceuticals

M.D. Anderson Cancer Center

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.

Laboratory Biomarker Analysis: Correlative studies

Questionnaire Administration: Ancillary studies

Smac Mimetic LCL161: Given PO

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
LCL161 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis	NCT02098161	Polycythemia Ve... Primary Myelofi... Secondary Myelo...	Laboratory Biom... Questionnaire A... Smac Mimetic LC...	18 Years -	M.D. Anderson Cancer Center
LCL161 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis	NCT02098161	Polycythemia Ve... Primary Myelofi... Secondary Myelo...	Laboratory Biom... Questionnaire A... Smac Mimetic LC...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for smac mimetic lcl161