Zevalin and Velcade in Relapsed/Refractory Mantle Cell Lymphoma

A Phase II Study Evaluating Combined Zevalin(Ibritumomab Tiuxetan)and Velcade(Bortezomib)in Relapsed/Refractory Mantle Cell Lymphoma

The purpose of this study is to evaluate the effects (good and bad) of the combination of ibritumomab tiuxetan (Zevalin) and bortezomib (Velcade) in patients with relapsed/refractory mantle cell lymphoma.

Zevalin is a monoclonal antibody that is combined with a radioactive substance and given with another monoclonal antibody called rituximab (Rituxan). It works by attaching to cancer cells and releasing radiation to damage those cells. Both Zevalin and Rituxan are given in this study, along with Velcade.

Study Overview

• Status: Terminated
• Conditions: Mantle-Cell Lymphoma
• Intervention / Treatment: Drug: Rituximab, Bortezomib,Y90 ibritumomab tiuxetan

Detailed Description

This is a non-randomized, unblinded single arm Phase II trial to evaluate the combination of yttrium90 ibritumomab tiuxetan and bortezomib in patients with relapsed/refractory mantle cell lymphoma (MCL). Standard hematology and chemistries, imaging and bone marrow biopsies will be done.

Research tests: 17cc of blood will be collected at screen, Day 8 OR 11 and month 3. Samples will be collected and stored for future analysis. These analyses may include but are not limited to measurements of proteasome inhibition. No genetic studies will be performed on these samples. Samples will be destroyed at the end of the study.

Primary Objective Estimate the overall response rate (CR + PR) of the combination of bortezomib and ibritumomab tiuxetan in patients with relapsed/refractory mantle cell lymphoma.

Secondary Objectives

• Estimate the progression free and overall survival in patients with relapsed/refractory mantle cell lymphoma who receive bortezomib and ibritumomab tiuxetan.
• Assess the toxicity of the combination of bortezomib and ibritumomab tiuxetan in patients with relapsed/refractory MCL.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with relapsed or refractory Mantle Cell lymphoma with measurable disease.
• Age > 18 years old
• Expected survival >/= 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 at initiation of study (Appendix I).
• Laboratory tests meet the levels specified in the protocol

Exclusion Criteria:

• Patients must not have received chemotherapy, radiation or surgical resection of malignancy within 3 weeks of study initiation. However, if they have received nitrosurea or mitomycin C then they should not be enrolled in the study until 6 weeks after therapy was last received.
• No limitations to number of prior therapies
• No prior radioimmunotherapy (RIT)
• Prior bortezomib is allowed
• Patient must be fully recovered from all toxicities associated with prior surgery, radiation treatment, chemotherapy or immunotherapy.
• No active, serious infection or medical or psychiatric illness likely to interfere with participation in this clinic trial
• No known HIV infection
• No active central nervous system (CNS) involvement
• Bone Marrow Involvement >/= 25% within 30 days of initiation of study treatment
• Pregnant or breast feeding
• No patients who have received Granulocyte colony-stimulating factor (G-CSF) or Granulocyte macrophage colony-stimulating factor (GM-CSF) within the 14 days prior to initiating protocol
• No patient who has had major surgery within the four weeks prior to initiating protocol therapy
• No patients with pleural effusion or significant ascites

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Zevalin + Velcade; Drug: Rituximab, Bortezomib,Y90 ibritumomab tiuxetan Other Names: Rituxan Velcade Zevalin Rituximab 250mg/m2 will be given on day 1 and on day 8. Bortezomib 1.5mg/m2 will be given on Days 1, 4, 8, and 11. Y90 ibritumomab tiuxetan will be given on Day 8. Dosage will be based on the platelet count obtained at the time of study enrollment. The dose will be 0.4 millicurie (mCi)/kg unless the enrollee's platelets are between 100,000 and 150,000 in which case a dose of 0.3mCi/Kg will be used. Patients who weigh over 80 Kg will receive a maximum dose of 32mCi.

Drug: Rituximab, Bortezomib,Y90 ibritumomab tiuxetan; Rituximab 250mg/m2 will be given on day 1 and on day 8. Bortezomib 1.5mg/m2 will be given on Days 1, 4, 8, and 11. Y90 ibritumomab tiuxetan will be given on Day 8. Dosage will be based on the platelet count obtained at the time of study enrollment. The dose will be 0.4mCi/kg unless the enrollee's platelets are between 100,000 and 150,000 in which case a dose of 0.3mCi/Kg will be used. Patients who weigh over 80 Kg will receive a maximum dose of 32mCi.; Other Names: Velcade; Rituxan; Zevalin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate (Complete Response + Partial Response)	Disease will be assessed every 3 months. The Cheson criteria will be used to define response: Complete Response = Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present prior to therapy. Partial Response = A decrease of ≥ 50% in the sum of the products of their greatest transverse diameters (SPD) of up to six of the largest dominant nodes or nodal masses. These nodes or masses should be selected according to the following features: a) they should be clearly measurable in at least two perpendicular measurements; b) they should be from as disparate regions of the body as possible; and c) they should include mediastinal and retroperitoneal areas of disease whenever these sites are involved.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Progression Free Survival	Progression-free survival will be defined as time from on-study to disease progression or death, whichever comes first	6 months
Overall Survival at 1 Year	Number of participants who were alive at the 1 year time point. (Overall survival will be defined as the time from on-study to death due to any cause.)	1 year
Overall Survival at 5 Year	Number of participants who were alive at the 5 year time point. (Overall survival will be defined as the time from on-study to death due to any cause.)	5 year

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: December 20, 2011
• First Submitted That Met QC Criteria: December 20, 2011
• First Posted (Estimate): December 22, 2011

Study Record Updates

• Last Update Posted (Estimate): July 15, 2015
• Last Update Submitted That Met QC Criteria: June 18, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab; Bortezomib
• Other Study ID Numbers: Pro00032517