Trial of PCI-32765 (BTK Inhibitor) in Combination With Carfilzomib in Relapse/Refractory Mantle Cell Lymphoma

NCT02269085 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 2013-0677NCI-2014-02495
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of carfilzomib and ibrutinib that can be given to patients with relapsed or refractory MCL. Researchers also want to learn if carfilzomib and ibrutinib can help to control the disease. This is an investigational study. Ibrutinib is FDA approved and commercially available to treat MCL and chronic lymphocytic leukemia (CLL). Carfilzomib is FDA approved and commercially available to treat certain types of multiple myeloma. Giving carfilzomib to patients with MCL is investigational. The combination of ibrutinib and carfilzomib is investigational. The study doctor can explain how the study drugs are designed to work. Up to 35 participants will be enrolled on this study. All will be enrolled at MD Anderson.

Conditions

Lymphoma

Keywords

Lymphoma; Mantle cell lymphoma; MCL; Relapsed or refractory; Ibrutinib; PCI-32765; Imbruvica; Carfilzomib

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Carfilzomib When Given With Ibrutinib

  MTD is defined as highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). DLT assessed during the first course of each cohort (28 days), and refers to a study drug related or possibly related event which meets one of the following criteria using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

  28 days

Secondary Outcomes (1)

• Response Rate of Carfilzomib When Given With Ibrutinib

  Assessed after two 28 day cycles

Study Arms (1)

Ibrutinib + Carfilzomib

EXPERIMENTAL

Phase I: Ibrutinib administered by mouth daily at 420 or 560 mg on Days 1 - 28 of a 28-day cycle. Carfilzomib administered by vein 20/27 mg/m\^2, 20/36 mg/m\^2, 20/45 mg/m\^2 or 20/56 mg/m\^2 on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle for Cycles 1- 12 and on Days 1, 2, 15 and 16 for Cycle 13 and higher. Phase II: Once the MTD has been established 5 additional patients treated at the MTD to a maximum of 35 patients with MCL. Study staff calls participant after end-of-dosing visit every 6 months for 5 years.

Drug: Ibrutinib; Drug: Carfilzomib; Behavioral: Phone Calls

Interventions

Ibrutinib DRUG

Phase I Starting Dose: 420 mg by mouth daily on Days 1 - 28 of a 28-day cycle. Phase II Starting Dose: MTD from Phase I.

Also known as: PCI-32765, Imbruvica

Ibrutinib + Carfilzomib

Carfilzomib DRUG

Phase I Starting Dose: 20 mg/m2 by vein on Days 1, 2, 8 ,9, 15 and 16 in Cycles 1 - 12, and Days 1,2 and 15,16 of Cycle 13 and beyond. Phase II Starting Dose: MTD from Phase I.

Ibrutinib + Carfilzomib

Phone Calls BEHAVIORAL

Study staff calls participant after end-of-dosing visit every 6 months for 5 years. These calls should take about 2-3 minutes.

Ibrutinib + Carfilzomib

Eligibility Criteria

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

You may qualify if:

• Patients must have a confirmed diagnosis of mantle cell lymphoma with positivity in tissue biopsy.
• Patients must have previously treated relapsed and/or refractory MCL with at least 2 prior lines of therapy (prior carfilzomib, ibrutinib, bortezomib, anthracycline, rituximab or stem cell transplant are acceptable). There is no upper limit for prior lines of therapy.
• Understand and voluntarily sign an institutional review board (IRB)-approved informed consent form.
• Age \>/= 18 years at the time of signing the informed consent.
• Patients must have bi-dimensional measurable disease (Measureable disease by CT scan defined as at least 1 lesion that measures =/\>1.5 cm in single dimension.) Patient with leukemia phase (peripheral blood involvement), non-measurable disease, gastrointestinal (GI) MCL, or bone marrow (BM) MCL are also eligible.
• Gastrointestinal or bone marrow or spleen only patients are allowable and will be analyzed separately.
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
• Serum bilirubin \<1.5 mg/dl and creatinine (Cr) Clearance \>/= 30 mL/min, platelet count \>75,000/mm\^3 and absolute neutrophil count (ANC) \> 1,500/mm\^3, aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) \< 3 x upper limit of normal or \< 5 x upper limit of normal if hepatic metastases are present. (Patients who have bone marrow infiltration by MCL are eligible if their ANC is \>/= 1000/mm\^3 \[growth factor not allowed\] or their platelet level is \>/= 50,000/mm\^3).
• Willing and able to participate in all study related procedures and therapy including swallowing capsules without difficulty.
• Females of childbearing potential (FCBP)\* must have a negative serum or urine pregnancy test and must be willing to use acceptable methods of birth control during the study and for 30 days after the last dose of study treatment. \* A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• Male patients must use an effective barrier method of contraception during the study and for 30 days following the last dose of study treatment if sexually active with a female of childbearing potential.

You may not qualify if:

• Any serious medical condition including but not limited to, uncontrolled hypertension, uncontrolled diabetes mellitus, uncontrolled infection, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), renal failure, active hemorrhage, or psychiatric illness that, in the investigators opinion places the patient at unacceptable risk and would prevent the subject from signing the informed consent form.
• Pregnant or breastfeeding females.
• Use of any standard/experimental anti-lymphoma drug therapy, including steroids, within 3 weeks of initiation of the study or use of any experimental non-drug therapy (e.g., donor leukocyte/mononuclear cell infusions) within 56 days of initiation of the study drug treatment.
• Prior allogeneic stem cell transplant (SCT) within 16 weeks or autologous SCT within 8 weeks of initiation of therapy. (Patients that require immunosuppressive therapy are not eligible within 60 days of therapy.)
• Known human immunodeficiency virus (HIV) infection. Patients with active Hepatitis B infection (not including patients with prior Hepatitis B vaccination; or positive serum Hepatitis B antibody). Hepatitis C infection is allowed as long as there is no active disease and is cleared by GI consultation.
• All patients with central nervous system lymphoma.
• Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to enrollment.
• Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).
• Contraindication to any of the required concomitant drugs or supportive treatments or intolerance to hydration due to preexisting pulmonary or cardiac impairment including pleural effusion requiring thoracentesis or ascites requiring paracentesis.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or any other gastrointestinal condition that could interfere with the absorption and metabolism of ibrutinib.
• Major surgery within 4 weeks of initiation of therapy.
• Requires anticoagulation with warfarin or equivalent vitamin K antagonist.
• Requires treatment with strong CYP3A inhibitors.
• The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient's health and survival, than of the MCL, within the subsequent 6 months at the time of consent. Investigator discretion is allowed.
• Patients with New York Heart Association (NYHA) Class III and IV heart failure, myocardial infarction in the preceding 6 months, and significant conduction abnormalities, including but not limited to atrial fibrillation, 2nd degree AV block type II, 3rd degree block, Torsade de pointe, QT prolongation (QTc \> 450 msec, sick sinus syndrome, ventricular tachycardia, symptomatic bradycardia (heart rate \< 50 bpm), hypotension, light headedness and syncope. Patients with atrial fibrillation will be excluded even if they are rate-controlled. If there are any active cardiac issues, cardiology consultation will be obtained for clearance.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Pharmacyclics LLC.: collaborator
• Amgen: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma; Lymphoma, Mantle-Cell; Recurrence

Interventions

ibrutinib; carfilzomib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Hun J. Lee, MD

  M.D. Anderson 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: October 16, 2014
• First Posted: October 20, 2014
• Study Start: April 20, 2015
• Primary Completion: May 29, 2018
• Study Completion: May 29, 2018
• Last Updated: February 28, 2019

Record last verified: 2019-02

Locations

US (1)