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

Primary Purpose

Refractory Diffuse Large B-cell Lymphoma

Status

Not yet recruiting

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Rituximab Paclitaxel Ruxolitinib

About this trial

This is an interventional treatment trial for Refractory Diffuse Large B-cell Lymphoma

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

single arm

Arm Description

ruxolitinib, paclitaxel, and rituximab

Outcomes

Primary Outcome Measures

Primary Outcome Measure

The tumor response will be assessed according to IWG Response Criteria.

Secondary Outcome Measures

Full Information

NCT ID

NCT04856137

First Posted

November 26, 2019

Last Updated

April 19, 2021

Sponsor

National Health Research Institutes, Taiwan

Collaborators

Taipei Veterans General Hospital, Taiwan, Chang Gung Memorial Hospital, China Medical University Hospital, Shin Kong Wu Huo-Shih Memorial Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04856137

Brief Title

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

Acronym

DLBL

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Not yet recruiting

Study Start Date

May 1, 2021 (Anticipated)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Health Research Institutes, Taiwan

Collaborators

Taipei Veterans General Hospital, Taiwan, Chang Gung Memorial Hospital, China Medical University Hospital, Shin Kong Wu Huo-Shih Memorial Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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%.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Refractory Diffuse Large B-cell Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Phase Ib Dose Escalation All patients received: Rituximab 375mg/m2 on D1 of each cycle, and Paclitaxel 200mg/m2 on D1 of each cycle, plus, G-CSF 1PC sc qd, starting D7 until ANC recovery Ruxolitinib continuously given (D1-21) in the following dose schema Phase II Efficacy Study All patients received: Rituximab 375mg/m2 on D1 of each cycle, and Paclitaxel 200mg/m2 on D1 of each cycle, plus Ruxolitinib using RP2D daily on D1-21 G-CSF 1PC sc qd, starting D7 until ANC recovery Repeat every 21 days

Masking

None (Open Label)

Allocation

N/A

Enrollment

74 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

single arm

Arm Type

Experimental

Arm Description

ruxolitinib, paclitaxel, and rituximab

Intervention Type

Drug

Intervention Name(s)

Rituximab Paclitaxel Ruxolitinib

Other Intervention Name(s)

G-CSF 1PC sc qd

Intervention Description

Rituximab 375mg/m2 on D1 of each cycle Paclitaxel 200mg/m2 on D1 of each cycle Ruxolitinib continuously given (D1-21)

Primary Outcome Measure Information:

Title

Primary Outcome Measure

Description

The tumor response will be assessed according to IWG Response Criteria.

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with relapsed/refractory CD20+ diffuse large B-cell lymphoma. Age greater than 20 years and younger than 75 years old. Measurable disease Patients must have an ECOG performance status of less than or equal to 2. Patients must have recovered from toxic effects of all prior therapy before entering onto study. A treatment of drug-free interval of at least 3 weeks since the last dose of chemotherapy is required. More than 4 weeks since prior radiotherapy is required. Adequate bone marrow function Adequate renal function with calculated glomerular filtration rate > 15 mL/min Patients must have adequate liver function All patients must sign a document of informed consent indicating their awareness of the investigational nature and the risks of the study. Exclusion Criteria: Patients who have prior treatment with ruxolitinib or taxane for DLBCL. Pregnant or breast-feeding females. Active or uncontrolled infection. Life expectancy < 6 months Patients with brain or leptomeningeal metastases. Known hypersensitivity to ruxolitinib or paclitaxel Grade III peripheral neuropathy secondary to prior to therapy Second malignancy, except indolent cancers not on active anti-cancer therapy.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Chih-Cheng Chen, M.D. Ph.D.

Phone

886-5-3621000

Ext

2852

ccchen1968@gmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Hui-Jen Tsai, M.D. Ph.D.

Phone

886-6-7000123

Ext

65149

hjtsai@nhri.edu.tw

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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