Phase 2 LCL-161 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF) or Post-Essential Thrombocytosis Myelofibrosis (Post-ET MF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02098161
Recruitment Status : Recruiting
First Posted : March 27, 2014
Last Update Posted : February 5, 2018
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
To goal of this clinical research study is to learn if LCL161 can help to control myelofibrosis. The safety of this drug will also be studied.

Condition or disease Intervention/treatment Phase
Leukemia Drug: LCL-161 Behavioral: Questionnaires Other: Phone Calls Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : December 2014
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Experimental: LCL-161
Starting dose of LCL-161 1500 mg by mouth on Days 1, 8, 15, and 22 of each 28 day cycle. Participants remain on study treatment, in the absence of disease progression or toxicity warranting discontinuation of therapy, as long as there is evidence of clinical benefit, as judged by the treating physician.
Drug: LCL-161
Starting dose of LCL-161 1500 mg by mouth on Days 1, 8, 15, and 22 of each 28 day cycle.

Behavioral: Questionnaires
Questionnaire completion at baseline, day 1 of cycle 2 and beyond, and at end of treatment visit. The questionnaires should take about 5-10 minutes to complete.
Other Name: Surveys

Other: Phone Calls
Study staff to call participant 1 time each month, and at 30 days after end of treatment visit.

Primary Outcome Measures :
  1. Objective Response (OR) of LCL-161 [ Time Frame: After 3, 28 day cycles ]
    Objective response (OR), defined as CR (complete remission) + PR (partial remission) + CI (clinical improvement) for myelofibrosis (MF) patients after 3 cycles of treatment. Categorized according to the International Working Group (IWG) consensus criteria for myelofibrosis .

Secondary Outcome Measures :
  1. Time to Response [ Time Frame: Day 1 of third, 28 day cycle ]
    Time to response defined as 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 censored at the subject's last evaluation date. The distribution for each of these event-time variables (duration of response and time to response) estimated by Kaplan-Meier curves.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients must provide written informed consent.
  2. Age 18 years or older.
  3. Willing and able to comply with scheduled visits, treatment plan and laboratory tests
  4. Patient is able to swallow and retain oral medication
  5. Must be diagnosed with treatment requiring PMF or post ET/PV MF with intermediate-1, intermediate -2 or high risk disease according to the 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.
  6. Patients who are not candidates for, intolerant, or relapsed/refractory to Ruxolitinib
  7. ECOG performance status 0-2
  8. Required baseline laboratory status: Absolute neutrophil count (ANC) >/= 0.5 x 109/L (1500/mm3); Serum direct bilirubin </= 2.0 x ULN (upper limit of normal); AST (SGOT) and ALT (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
  9. Treatment-related toxicities from prior therapies must have resolved to Grade </= 1
  10. At least 2 weeks from prior MF-directed treatment (till the start of study drug)

Exclusion Criteria:

  1. 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.
  2. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: History or presence of ventricular tachyarrhythmia; Presence of unstable atrial fibrillation (ventricular response > 100 bpm). Patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria. Clinically significant resting bradycardia (< 50 bpm). Angina pectoris or acute myocardial infarction </= 3 months prior to starting study drug. Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen).
  3. 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
  4. Patients who are currently receiving treatment with agents that are metabolized solely through CYP3A4/5 and have a narrow therapeutic index or are strong CYP2C8 inhibitors; or are receiving treatment with agents that carry a risk for QT prolongation and are CYP3A substrates.
  5. Patients with impairment of GI function or GI disease that may significantly alter the absorption of LCL161 as per physicians opinion
  6. 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-HCG laboratory test.
  7. 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.
  8. Continued from #7 above: 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.
  9. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02098161

Contact: Naveen Pemmaraju, MD 713-792-4956

United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Principal Investigator: Naveen Pemmaraju, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT02098161     History of Changes
Other Study ID Numbers: 2013-0612
NCI-2014-01241 ( Registry Identifier: NCI CTRP )
First Posted: March 27, 2014    Key Record Dates
Last Update Posted: February 5, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Primary Myelofibrosis
Post-Polycythemia Vera Myelofibrosis
Post-PV MF
Post-Essential Thrombocytosis Myelofibrosis
Post-ET MF
Phone Call

Additional relevant MeSH terms:
Primary Myelofibrosis
Polycythemia Vera
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders