A Phase I/II Study of Diffuse Large B-cell Lymphoma (DLBL)

A Phase I/II Study of Relapse/Refractory Diffuse Large B-cell Lymphoma

For continuous variables, mean, median, minimum, and maximum will be used for the descriptive purpose. For categorical variables, frequency and percentage will be used for descriptive statistics. The variables of OS will be estimated by the Kaplan-Meier method. Differences between groups will be calculated using the log-rank test for univariate analysis. Cox's proportional hazards model will be employed to test independent prognostic factors. All calculations will be performed using the Statistical Package of Social Sciences software, version 17.0 (SPSS, Inc., Chicago, IL, USA). The level of statistical significance will be set at 0.05 for all tests.

Study Overview

• Status: Not yet recruiting
• Conditions: Refractory Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: Rituximab Paclitaxel Ruxolitinib

Detailed Description

This is an open-label, single arm, prospective, multiple-center phase Ib/II study.

In phase Ib, a maximum of 18 patients will be enrolled in the dose-finding period to determine the RP2D, dependent on the toxicity of the study drugs. The response rates of salvage chemotherapy regimen in R/R DLBCL were reported to be within the range of 35-65%.3 Assuming that the response rate of traditional salvage therapy has an overall response rate of 35% (H0=0.35) and that our experimental regimen would increase it to 50% (H1=0.50), the estimated sample size according to the Simon's two-stage minimal design will be 49 in the second phase.1 Briefly, among the 31 patients recruited during the first stage, the response should be seen in at least 10 of the cases, the lowest threshold for the trial to be moved into the second stage of the phase II part. Furthermore, for the RPR regimen to be deemed effective, a response must be demonstrated in at least 21 of the whole 49 patients enrolled in the phase II period. This would achieve a power of 80%, with a two-sided type I error rate of 10%. An additional 7 patients will be recruited, for an estimated dropout rate of 10%.

• Study Type: Interventional
• Enrollment (Anticipated): 74
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Chih-Cheng Chen, M.D. Ph.D.; Phone Number: 2852 886-5-3621000; Email: ccchen1968@gmail.com
• Study Contact Backup: Name: Hui-Jen Tsai, M.D. Ph.D.; Phone Number: 65149 886-6-7000123; Email: hjtsai@nhri.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with relapsed/refractory CD20+ diffuse large B-cell lymphoma.
2. Age greater than 20 years and younger than 75 years old.
3. Measurable disease
4. Patients must have an ECOG performance status of less than or equal to 2.
5. Patients must have recovered from toxic effects of all prior therapy before entering onto study.
6. A treatment of drug-free interval of at least 3 weeks since the last dose of chemotherapy is required.
7. More than 4 weeks since prior radiotherapy is required.
8. Adequate bone marrow function
9. Adequate renal function with calculated glomerular filtration rate > 15 mL/min
10. Patients must have adequate liver function
11. All patients must sign a document of informed consent indicating their awareness of the investigational nature and the risks of the study.

Exclusion Criteria:

1. Patients who have prior treatment with ruxolitinib or taxane for DLBCL.
2. Pregnant or breast-feeding females.
3. Active or uncontrolled infection.
4. Life expectancy < 6 months
5. Patients with brain or leptomeningeal metastases.
6. Known hypersensitivity to ruxolitinib or paclitaxel
7. Grade III peripheral neuropathy secondary to prior to therapy
8. Second malignancy, except indolent cancers not on active anti-cancer therapy.

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: single arm; ruxolitinib, paclitaxel, and rituximab	Drug: Rituximab Paclitaxel Ruxolitinib; Rituximab 375mg/m2 on D1 of each cycle Paclitaxel 200mg/m2 on D1 of each cycle Ruxolitinib continuously given (D1-21); Other Names: G-CSF 1PC sc qd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome Measure	The tumor response will be assessed according to IWG Response Criteria.	1 year

Collaborators and Investigators

• Sponsor: National Health Research Institutes, Taiwan
• Collaborators: China Medical University Hospital; Chang Gung Memorial Hospital; Taipei Veterans General Hospital, Taiwan; Shin Kong Wu Huo-Shih Memorial Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2021
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2028

Study Registration Dates

• First Submitted: November 26, 2019
• First Submitted That Met QC Criteria: April 19, 2021
• First Posted (ACTUAL): April 23, 2021

Study Record Updates

• Last Update Posted (ACTUAL): April 23, 2021
• Last Update Submitted That Met QC Criteria: April 19, 2021
• Last Verified: March 1, 2021

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, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Paclitaxel; Rituximab
• Other Study ID Numbers: T1420

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No