A Study of Ixazomib and Ibrutinib in Relapsed/Refractory Mantle Cell Lymphoma

Phase 1

Completed

Brief Summary: Patients with mantle cell lymphoma (MCL) that has relapsed (come back) or refractory (progressed on treatment) will receive ixazomib and ibrutinib.

Ibrutinib has been approved by the Food and Drug Administration (FDA) as treatment for patients with mantle cell lymphoma who have received at least one prior therapy.

Ixazomib is in a class of medications called proteasome inhibitors. Cancer cells depend on proteasome to provide this protein metabolism (turnover) function to regulate their growth and survival. Ixazomib disrupts a cancer cells' ability to survive by blocking the proteasome and disrupting protein metabolism. This may help to slow down the growth of cancer or may cause cancer cells to die.

The purpose of this study is to see whether the addition of ixazomib to ibrutinib chemotherapy is effective in treating people who have relapsed or refractory MCL and to examine the side effects associated with ixazomib in combination with ibrutinib.

Detailed Description: MCL is a rare subtype of non-Hodgkin lymphoma that is considered incurable with conventional therapy. For relapsed patients, Ibrutinib, lenalidomide, and bortezomib are all approved by the FDA but are not curative. Novel approaches are required to improve outcomes for patients with relapsed/refractory MCL.

This is an open-label study that will be done in 2 phases. Phase I will test different doses of ixazomib and ibrutinib to determine the maximum safe and tolerated dose. In Phase I, patients who have already received ibrutinib, may participate if they meet certain criteria (i.e., have not received ibrutinib for at least 3 months).

Phase II will find out the effects, good and/or bad, of ixazomib in combination with ibrutinib. In Phase II, patients will be separated into 2 groups, patients who have never received a Bruton's Tyrosine Kinase (BTK) inhibitor and patients who have received a BTK inhibitor. This study is designed to examine the effectiveness of this drug in treating patients with MCL.

Patients will be treated until progression or unacceptable toxicity.

Tumor assessments will be performed approximately every 3 months for the first year of treatment, then every 6 months until progression.

Mandatory bone marrow and tumor tissue samples (i.e., obtained during a previous procedure or biopsy) are required at baseline. Mandatory research blood samples will also be collected.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Phase I: Ixazomib & Ibrutinib	Ibrutinib	Ixazomib and Ibrutinib will be given by mouth until progression or unacceptable toxicity.
Phase I: Ixazomib & Ibrutinib	Ixazomib	Ixazomib and Ibrutinib will be given by mouth until progression or unacceptable toxicity.
Phase II: Ixazomib & BTK-Naive	Ibrutinib	Patients who are BTK-Naive will receive Ixazomib and Ibrutinib by mouth until progression or unacceptable toxicity.
Phase II: Ixazomib & BTK-Naive	Ixazomib	Patients who are BTK-Naive will receive Ixazomib and Ibrutinib by mouth until progression or unacceptable toxicity.
Phase II: Ixazomib & BTK Pre-Treated (Closed 8/7/2020)	Ibrutinib	Patients previously treated with a BTK will receive Ixazomib and Ibrutinib by mouth until progression or unacceptable toxicity.
Phase II: Ixazomib & BTK Pre-Treated (Closed 8/7/2020)	Ixazomib	Patients previously treated with a BTK will receive Ixazomib and Ibrutinib by mouth until progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Phase I: Dose Limiting Toxicities (DLT) Rate	1 month	To determine the maximum tolerable dose (MTD) of ixazomib (mg) in combination with ibrutinib (mg) in patients with relapsed/refractory mantle cell lymphoma (MCL) using DLT endpoint.
Phase II: Complete Response Rate	12 months	CR rate will be the defined as the percentage of patients achieving CR as confirmed by bone marrow biopsy within the first 12 months of initiating treatment. Response to treatment was assessed using the Lugano classification criteria. Patients completed a PET/CT at the time of study enrollment and were restaged at cycles 3, 6, 9, and 12, and then every 6 months while on study therapy. All patients with suspected CR who had bone marrow involvement at screening underwent a bone marrow biopsy to confirm response.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Phase I & II: 48 months	OS assessed during clinic visit or by reaching out to patients to confirm vital status.
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0	Phase I: 12 months; Phase II: 36 months	Number of patients with abnormal laboratory values and/or adverse events (defined as a new untoward medical occurrence or worsening of a pre-existing medical condition) related to study treatment. Grades refer to the severity of the adverse event, where grade 1 through 5 signifies mild, moderate, severe, life-threatening, and death respectively.
Overall Response Rate (ORR)	Phase I: 12 months; Phase II: 12 months	ORR assessed in accordance with Lugano classification
Progression-Free Survival (PFS)	Phase I & II: 48 months	PFS assessed in accordance with Lugano classification

Locations (14): Winship Cancer Institute of Emory University
🇺🇸
Atlanta, Georgia, United States
Georgia Cancer Center at Augusta University
🇺🇸
Augusta, Georgia, United States
Carle Cancer Center
🇺🇸
Urbana, Illinois, United States
University of Kansas
🇺🇸
Overland Park, Kansas, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Rutgers Cancer Institute of New Jersey
🇺🇸
New Brunswick, New Jersey, United States
Laura and Isaac Perlmutter Cancer Center at NYU
🇺🇸
New York, New York, United States
University of Pennsylvania Abramson Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
University of Virginia
🇺🇸
Charlottesville, Virginia, United States
West Virginia University
🇺🇸
Morgantown, West Virginia, United States
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Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States