Lenalidomide, Ixazomib, and Rituximab as Front-Line Therapy for High Risk Indolent B-Cell Lymphoma

NCT02898259 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: CASE1414
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase IB/II Trial of Lenalidomide (Revlimid®), Ixazomib and Rituximab (RIXAR) as Front-line Therapy for High Risk Indolent B cell Lymphoma

Conditions

B Cell Lymphoma; Lymphoma

Keywords

Lenalidomide; Ixazomib; Rituximab

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Oral Ixazomib

  To determine the MTD of the combination of oral ixazomib and lenalidomide plus rituximab in patients with previously untreated low-grade B cell lymphoma having high tumor burden by GELF criteria or FLIPI 3-5. MTD will be determined using the first 12 participants 15 months after beginning treatment

  15 months after beginning treatment

Secondary Outcomes (6)

• Overall Response Rate

  Up to 15 months after beginning treatment

• Duration of Response

  Up to 15 months after beginning treatment

• Time to Progression

  Up to 15 months after beginning treatment

• Progression Free Survival

  Up to 15 months after beginning treatment

• Time to Treatment Failure

  Up to 15 months after beginning treatment

Study Arms (1)

Lenalidomide + Ixazomib + Rituximab

EXPERIMENTAL

Ixazomib will be orally administered with a starting dose of 2.0mg. Lenalidomide will be administered orally with a starting dose of 20mg. Rituximab will be administered intravenously at the standard dose of 375mg/m2. The study will use a standard 3 + 3 design for determination of MTD during cycle 1. There will be three dose levels for escalation, followed by two expansion cohorts of 12 patients each at the MTD, one cohort with follicular lymphoma and one cohort with non-follicular low-grade lymphoma (SLL, marginal zone, lymphoplasmacytic). Patients will be treated for 12 cycles of 4 week duration.

Drug: Ixazomib; Drug: Lenalidomide; Drug: Rituximab

Interventions

Ixazomib DRUG

The prescribed administration of ixazomib doses in this study is 2.0, 3.0 or 4.0 mg ixazomib on days 1, 8 and 15 of each 28 day cycle.

Lenalidomide + Ixazomib + Rituximab

Lenalidomide DRUG

Lenalidomide starting dose will be based on baseline calculated creatinine clearance as follows: * Starting lenalidomide Dose (20mg) * Calculated Creatinine Clearance: \>=60ml/min receive 20 mg daily on Days 1 - 21 of each 28-day cycle * Calculated Creatinine Clearance: \>= 30 and \< 60 ml/min receive 10 mg daily on Days 1 - 21 of each 28-day cycle

Also known as: Revlimid

Lenalidomide + Ixazomib + Rituximab

Rituximab DRUG

Rituximab is administered intravenously at 375mg/m2 on days 1, 8, and 15 of cycle 1, day 1 of cycles 2-6 and day 1 of cycles 8, 10, and 12.

Also known as: Rituxan

Lenalidomide + Ixazomib + Rituximab

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 histologically confirmed, low-grade B-lymphocyte Non-Hodgkin's Lymphoma (NHL) by the World Health Organization Classification:
• Follicular lymphoma grades 1, 2, and 3a
• Marginal zone B-cell lymphoma, including extranodal (MALT), nodal and splenic. Excluding: Small lymphocytic lymphoma Lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (WM)
• Lymphoplasmacytic lymphoma (including Waldenström's macroglobulinemia (WM))
• Must have stage 2, 3 or 4 disease, with either high tumor burden by Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria and/or Follicular Lymphoma International Prognostic Index (FLIPI) 3-5
• To meet GELF criteria, patient must have at least one criterion:
• Nodal or extranodal mass \> 7 cm
• At least 3 nodal masses: each \> 3.0 cm in longest dimension
• Systemic symptoms due to lymphoma or B symptoms
• Splenomegaly with spleen \> 16 cm by Computed Tomography (CT) scan
• Evidence of compression syndrome (e.g., ureteral, orbital, gastrointestinal) or pleural or peritoneal serous effusion due to lymphoma (irrespective of cell content)
• Leukemic presentation (\> 5.0 x 10\^9/L malignant circulating follicular or lymphoma cells)
• Cytopenias (absolute neutrophil count \< 1.0 X 10\^9/L, hemoglobin \< 10 gm/dL, and/or platelets \<100 x 10\^9/L).
• AND/OR To meet FLIPI criteria, patient must have at least 3 out of the following 5 criteria:
• Age \> 60 years

You may not qualify if:

• Patients who are receiving any other investigational agents.
• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Major surgery within 14 days before enrollment.
• Radiotherapy within 14 days before enrollment. If the involved field is small (single nodal area), 7 days will be considered a sufficient interval between treatment and beginning of protocol therapy.
• Known central nervous system involvement.
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
• Systemic treatment, within 14 days before the beginning of protocol therapy, with CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort.
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. Specifically, prior desquamating rash or erythema nodosum during prior thalidomide or other similar agents.
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib or lenalidomide including difficulty swallowing.
• Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Patient has ≥ Grade 2 peripheral neuropathy on clinical examination during the screening period.
• Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.
• Any prior use of Revlimid® or Velcade®.
• Known seropositivity for, or active viral infection with, Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) (unless due to vaccination), or Hepatitis C Virus (HCV). HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with lenalidomide and ixazomib. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Sponsors & Collaborators

• Brian Hill: lead
• The Cleveland Clinic: collaborator

Study Sites (2)

University Hospitals, Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma

Interventions

ixazomib; Lenalidomide; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Brian Hill
• Organization: Clevleland

TaussigResearch@ccf.org

1-866-223-8100

Study Officials

• Brian Hill, MD, PhD

  Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD,PhD

Study Record Dates

• First Submitted: September 8, 2016
• First Posted: September 13, 2016
• Study Start: February 20, 2017
• Primary Completion: October 23, 2018
• Study Completion: June 6, 2022
• Last Updated: September 26, 2022
• Results First Posted: January 13, 2021

Record last verified: 2022-09

Locations

US (2)