Bortezomib in Combination With Ibrutinib in Ibrutinib Relapsed Mantle Cell Lymphoma

Study Overview
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Brief Summary
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This is a phase II study to evaluate the efficacy of ibrutinib in combination with bortezomib in in MCL (mantle cell lymphoma) patients who relapsed on single agent ibrutinib.

Official Title
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Phase II Study Evaluating the Effect of Adding Bortezomib to Ibrutinib in Ibrutinib Relapsed Mantle Cell Lymphoma

Conditions
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Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: Bortezomib
* Drug: Ibrutinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ≥ 18 years of age Diagnosis of mantle cell lymphoma established by histologic assessment by a hemato-pathologist with additional assessment of the histologic diagnosis by immunohistochemistry or flow cytometry. Patients with history of MCL that has relapsed (documented disease progression after previously responding) to therapy (CR/PR) on single agent ibrutinib (treated for at least 6 months) as the last treatment prior to enrollment. Adequate liver, renal and bone marrow function Adequate coagulation (unless abnormalities are unrelated to coagulopathy or bleeding disorder) Female subjects of childbearing potential must have a negative urine/serum pregnancy test upon study entry. Women as well are not advised to breastfeed during treatment with bortezomib and for 2 months after treatment. Male and female subjects of reproductive potential must agree to use both a highly effective method of birth control and barrier method during the period of therapy and for 30 days after the last dose of study drug for females and 90 days for males. Eastern Cooperative Oncology Group (ECOG) performance status of <2 (Eastern Cooperative Oncology Group scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 5 where 0 represents perfect health and 5 represents death.) Exclusion Criteria: Concurrent diagnosis of another malignancy unless treated with curative intent more than 2 years from study start (basal/squamous cell carcinoma of the skin is not an exclusion). Previous treatment with bortezomib. Patients who are eligible for autologous stem cell transplant are excluded unless they refuse this procedure. History of allogeneic stem cell transplant. Other exclusions (certain concurrent conditions) per protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bortezomib + Ibrutinib<br>Ibrutinib will be administered orally at a dose of 560 mg daily for each 21 day cycle. Bortezomib will be administered subcutaneously at a dose of 1.3 mg/m^2 on days 1, 4, 8, and 11 of each 21-day cycle. | Drug: Bortezomib<br>* Bortezomib will be administered subcutaneously at a dose of 1.3 mg/m^2 on days 1, 4, 8, and 11 of each 21-day cycle.<br>Drug: Ibrutinib<br>* Ibrutinib will be administered orally at a dose of 560 mg daily for each 21 day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants that respond to treatment at 6 months | The primary endpoint is overall response rate (ORR). Participants will be evaluated for response based on the Lugano criteria. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival time | Patients will be followed for survival until death or up to 10 years. | Up to 10 Years | 
| Progression free survival time | Progression will be determined using the Lugano criteria. Patients will be followed for survival until death or up to 10 years. | Up to 10 Years | 
| Best overall response | Participants will be evaluated for response based on the Lugano criteria. From the start of the study treatment until the disease progression/recurrence or up to 10 years. | Up to 10 Years | 
| Rate of complete response | Participants will be evaluated for response based on the Lugano criteria. The percentage of participants who achieve CR after treatment. | Up to 10 Years | 
| Time to progression | Progression will be determined using the Lugano criteria. | Up to 10 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed