Multicenter Study of Pacritinib Combined With Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

September 5, 2017 updated by: University of Michigan Rogel Cancer Center

Phase I/II, Open Label, Multicenter Study of Pacritinib Combined With Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

This study combines two drugs in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Investigators are proposing combining ibrutinib, an orally-administered, small molecule inhibitor of Bruton's tyrosine kinase (FDA approved for the treatment of relapsed/refractory CLL), with pacritinib, a novel JAK2-FLT3 inhibitor that has shown activity in relapsed lymphoma, including CLL/SLL. Investigators will first demonstrate the safety and tolerability of Pacritinib when combined with Ibrutinib in a phase I study, which will help establish the MTD (Maximum Tolerated Dose)of Pacritinib when combined with Ibrutinib. Once the optimal dose of Pacritinib is established in the phase I setting, a phase II evaluation will seek to establish the efficacy of the combination of Pacritinib with Ibrutinib. Patients will receive continuous treatment until progressive disease and will be followed while on study treatment for a total of 2 years.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 79 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of CLL/SLL
  • Relapsed or refractory CLL or SLL following at least 1 prior line of systemic therapy with active disease meeting criteria for treatment
  • Age ≥18 and <80
  • ECOG (Eastern Cooperative Oncology Group) ≤2 (This is a performance status that attempts to quantify a patients daily activities where 0 represents normal activity and 5 represents death)
  • Adequate organ function defined as AST and ALT ≤ 2 times upper limit of normal (ULN), Total Bilirubin ≤ 1.5 times ULN (exception of Gilbert disease), Renal function: CrCl ≥30 mL/min, Bazett-corrected Q-T interval ≤ 0.45 seconds
  • Peripheral blood counts of ANC >500 cells/μL, platelets ≥ 50,000 cells/ μL, Hemoglobin≥ 8 g/dL
  • Prior treatment allowed if: at least 30 days have elapsed since last chemotherapy and/or radiation and patient has recovered from all clinically significant treatment-related toxicity, or at least 90 days have passed since date of autologous stem cell transplant and patient has recovered to ≤grade 1 toxicity related to this procedure.
  • Ability to provide written informed consent
  • Ability to take oral medications.

Exclusion Criteria:

  • Pregnant or breast feeding women
  • Primary or metastatic CNS (Central Nervous System) disease prior to study enrollment
  • Uncontrolled current illness including, but not limited to, ongoing or active infections requiring intravenous antimicrobials, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia and/or psychiatric illness or social situations that would limit compliance with study requirements
  • Known HIV infection
  • Active infection with Hepatitis B or C virus
  • Concomitant therapy in last 30 days of any of the following: cytotoxic chemotherapy, immunosuppressive agents, other investigational therapies or chronic use of systemic corticosteroids
  • Prior treatment with ibrutinib
  • Uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP).
  • Requires anticoagulation with warfarin or equivalent Vit K antagonist
  • Allergy to either ibrutinib or pacritinib or components within medication
  • Treatment with strong CYP3A4 inducer or inhibitor, for which no alternative is available.
  • Unwilling or unable to use a medically acceptable form of contraception.
  • Any gastrointestinal or metabolic condition that could interfere with the absorption of oral medication.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pacritinib and Ibrutinib

Phase I: Patients will receive Pacritinib 100-200 mg twice daily along with Ibrutinib 420mg/day.

Phase II Lead-In: Pacritinib at MTD daily continuous x 2 months followed by Pacritinib at MTD twice daily along with Ibrutinib 420mg/day.
Drug: Ibrutinib
Drug: Pacritinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Then maximum tolerated dose (MTD) of Pacritinib when given in combination with Ibrutinib
Time Frame: 28 Days
DLTs (Dose Limiting Toxicities) occurring during the 1st cycle (first 28 days) of treatment with the combination of pacritinib and ibrutinib will be used for dose-escalation decisions. MTD is defined as the largest dose at which no more than 25% of patients experience a DLT.
28 Days
The number of patients with a Complete Response (CR)
Time Frame: 2 Years Post Treatment

Patients will be followed for response from the date of initial treatment until 2 years post treatment. CR is defined as:

Lymphadenopathy - None ˃1.5 cm Hepatomegaly - None Splenomegaly - None Blood Lymphocytes - ˂ 4000/μL Bone Marrow - Normocellular, 30% lymphocytes, no B-lymphoid nodules. Platelet Count - ˃ 100,000/μL Hemoglobin - ˃ 11.0 g/dL Neutrophils - ˃ 1,500/μL
2 Years Post Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan Rogel Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2016

Primary Completion (Anticipated)

October 1, 2018

Study Completion (Anticipated)

October 1, 2018

Study Registration Dates

First Submitted

February 4, 2016

First Submitted That Met QC Criteria

February 8, 2016

First Posted (Estimate)

February 9, 2016

Study Record Updates

Last Update Posted (Actual)

September 6, 2017

Last Update Submitted That Met QC Criteria

September 5, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCC 2015.131
  • HUM00105554 (Other Identifier: University of Michigan)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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