Safety and Efficacy of Rituximab for Treatment of Multicentric Castleman Disease in Malawi

LCCC 1950 - Rituximab for Multicentric Castleman Disease in Malawi, A Single-Arm Phase II Safety/Efficacy Trial

Sponsors

Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

Collaborator: Fogarty International Center of the National Institute of Health

Source UNC Lineberger Comprehensive Cancer Center
Brief Summary

The purpose of this study is to determine the safety and efficacy of first-line, risk-stratified Rituximab-based Multicentric Castleman Disease (MCD) treatment in Malawi in a single-arm, phase II clinical trial. This study also aims to compare the cost-effectiveness of first-line Rituximab treatment for MCD in Malawi to chemotherapy.

Detailed Description

This study aims to determine the safety and efficacy of first-line, risk-stratified rituximab-based MCD treatment in Malawi in a single-arm, phase II clinical trial. The investigators will enroll 27 subjects with newly diagnosed or previously treated MCD (who have not previously received rituximab) requiring treatment (B symptoms or hemoglobin <10 g/dL). Subjects will be treated with four weekly doses of rituximab. High-risk subjects (defined as patients with Eastern Cooperative Oncology Group (ECOG) performance status >2 or hemoglobin <8 g/dL) will also receive etoposide chemotherapy. Subjects will be followed for one year for toxicity and two years for survival. The primary outcome will be safety, defined as the frequency of ≥Grade 3 treatment-related Common Terminology Criteria for Adverse Events (AEs). Secondary outcomes will be event-free survival (death, progression, or development of NHL) and 1- and 2-year overall survival (OS). The investigators also aim to compare the cost-effectiveness of first-line rituximab treatment for MCD in Malawi to chemotherapy (using the investigators' historical controls).

Overall Status Not yet recruiting
Start Date October 2020
Completion Date August 2025
Primary Completion Date August 2023
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Rate of non-hematologic grade ≥3 adverse events 12 weeks
Treatment-related mortality rate 12 weeks
Secondary Outcome
Measure Time Frame
Characteristics of MCD presentation in Malawi 21 days, at study entry
Overall survival rate 2 years
Event-free survival survival rate 2 years
Clinical response rate 90 days
Radiologic response rate 90 days
Frequency of all Adverse Events 12 weeks
Rate of Kaposi sarcoma exacerbation 2 years
Change in Multicentric Castleman disease symptom score 2 years
Change in Quality of life PROMIS scores 2 years
Change in hemoglobin measurement Baseline, Day 15 and End of treatment (approximately 6 weeks)
Change in platelet count measurement Baseline, Day 15 and End of treatment (approximately 6 weeks)
Change in C-reactive protein measurement Baseline, Day 15 and End of treatment (approximately 6 weeks)
Change in Interleukin-6 measurement Baseline, Day 15 and End of treatment (approximately 6 weeks)
Change in Interleukin-10 measurement Baseline, Day 15 and End of treatment (approximately 6 weeks)
Change in Kaposi sarcoma herpesvirus viral load measurement Baseline, Day 15 and End of treatment (approximately 6 weeks)
Enrollment 27
Condition
Intervention

Intervention Type: Drug

Intervention Name: Rituximab

Description: 375 mg/m^2 administered via IV infusion weekly for four weeks. Administered via slow IV infusion, starting at 50mg/hr and increasing by 50mg/hr every 30 minutes to a maximum infusion rate of 400mg/hr.

Arm Group Label: Single Arm Rituximab

Other Name: Rituxan

Intervention Type: Drug

Intervention Name: Etoposide

Description: Subjects with high-risk disease will receive 100 mg/m^2 etoposide weekly for four weeks administered over one hour via IV infusion after completion of rituximab

Arm Group Label: Single Arm Rituximab

Eligibility

Criteria:

Inclusion Criteria: 1. Newly diagnosed or previously treated subjects with KSHV-associated MCD that is pathologically confirmed by characteristic histologic features and latency-associated nuclear antigen (LANA) positivity by Immunohistochemistry (IHC). 2. Age is greater than or equal 18 years old at time of consent. 3. Can provide informed consent. 4. HIV-infected or HIV-uninfected. 5. If HIV-infected, must be on or willing to start antiretroviral therapy including lamivudine or tenofovir. 6. Willing to comply with study visits. 7. MCD treatment indicated based on the presence of a symptomatic MCD flare, defined as the presence of each of the following three criteria: 1. Fever (subjective or objective) 2. Lymphadenopathy or hepatosplenomegaly 3. At least one of the following signs or symptoms attributable to MCD by the local study investigator: - Weight loss >5% - Malaise - Anemia (Hemoglobin <10 g/dL) - Thrombocytopenia (Platelets <100 x 103/mL) NOTE: If only two of the three criteria are present, but the provider feels treatment is indicated for a symptomatic MCD flare, this will be allowed after communication with the study principal investigator (PI). 8. Females of childbearing potential must have a negative urine pregnancy test within three days prior to registration. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided. 9. Females must agree to abstain from breast-feeding during therapy and for 30 days after the completion of therapy. 10. Females of childbearing potential must be willing to abstain from heterosexual activity or to use two forms of effective methods of contraception from the time of informed consent until 30 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method, or an intrauterine device that meets <1% failure rate for protection from pregnancy in the product label. 11. Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 30 days after the last dose of study therapy. Exclusion Criteria: 1. Symptomatic, extensive-stage KS (T1 by the AIDS Clinical Trials Group (ACTG) staging system; T1 includes ulceration or edema from KS, raised or non-hard palate oral lesions, or any visceral involvement) requiring urgent treatment, to avoid potential rituximab-induced KS worsening. 2. Previous rituximab use for MCD. 3. Second active malignancy requiring systemic therapy. 4. If HIV negative and a) hepatitis B virus surface antigen positive or b) combination of HepB core antibody positive and HepB surface antibody negative (indicative of chronic infection) unless on tenofovir or lamivudine. All HIV-infected patients must be on tenofovir or lamivudine as part of the inclusion criteria. 5. Active infection requiring systemic therapy. 6. Treatment with any investigational drug within 28 days prior to registration. 7. >7 days of corticosteroids. 8. Bilirubin >3 mg/dL. 9. Creatinine clearance <30 ml/min by Cockcroft-Gault formula. 10. ECOG performance status >3.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Matthew Painschab, MD Principal Investigator University of North Carolina
Overall Contact

Last Name: Matthew Painschab, MD

Phone: 763 234 5055

Email: [email protected]

Location
Facility: UNC Project, Kamuzu Central Hospital
Location Countries

Malawi

Verification Date

October 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Single Arm Rituximab

Type: Experimental

Description: The safety and efficacy of first-line rituximab will be assessed through a risk-stratified rituximab-based Multicentric Castleman disease (MCD) The planned sample size is 27 adult patients accrued at a rate of 10 patients annually. High-risk patients (defined as patients with ECOG performance status >2 or hemoglobin <8 g/dL) will receive four weekly doses of rituximab (375 mg/m2) and etoposide (100 mg/m2). Low-risk patients will receive the same dose of rituximab (four weekly doses at 375 mg/m2) alone.

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov