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

NCT02677948 | Withdrawn Phase 1 DMC

• 2 other identifiers: UMCC 2015.131HUM00105554
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia; Lymphoma, Small Lymphocytic

Outcome Measures

Primary Outcomes (2)

• Then maximum tolerated dose (MTD) of Pacritinib when given in combination with Ibrutinib

  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)

  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

Study Arms (1)

Pacritinib and Ibrutinib

EXPERIMENTAL

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: Pacritinib; Drug: Ibrutinib

Interventions

Pacritinib DRUG

Pacritinib and Ibrutinib

Ibrutinib DRUG

Pacritinib and Ibrutinib

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (2)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene; ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ryan Wilcox, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2016
• First Posted: February 9, 2016
• Study Start: October 1, 2016
• Primary Completion: October 1, 2018
• Study Completion: October 1, 2018
• Last Updated: September 6, 2017

Record last verified: 2017-09

Locations

US (2)