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Low Dose Vemurafenib and Rituximab in Hairy Cell Leukemia

Primary Purpose

Hairy Cell Leukemia

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Low dose vemurafenib plus rituximab

About this trial

This is an interventional treatment trial for Hairy Cell Leukemia

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

≥ 18 years of age
Histologically confirmed HCL that are BRAF V600E positive by IHC or NGS
Patient's must meet the standard treatment initiation criteria, as defined by ANC ≤1.0, Hgb ≤ 10.0 or PLT ≤100K
Patients can either have (1) not received any prior therapy for the disease or have had (2) failure to achieve any response to the initial purine analog-based therapy or (3) subsequent relapse after any prior therapy.
ECOG performance status of 0-2
Acceptable pre-study organ function during screening not exacerbated by Hairy Cell Leukemia. General thresholds should be a total bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN, and serum creatinine ≤ 1.5x ULN
For women of childbearing potential, agreement to use acceptable methods of contraception
For men with female partners of childbearing potential, agreement to use barrier contraception
Negative serum pregnancy test within 7 days of commencement of treatment in premenopausal women.
Ability to understand and willingness to sign a written informed consent document.
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

Pregnant or breast-feeding or intending to become pregnant during the study
Have had chemotherapy (including purine analogs), rituximab, and other investigational agents within six weeks prior to entering the study. The patients cannot have received BRAF inhibitor therapy within 6 months of entering the study.
Major surgery within 4 weeks prior to entering the study
Invasive malignancy within the past 2 years prior to first study drug administration, except for adequately treated (with curative intent) basal or squamous cell carcinoma, melanoma, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, or limited stage bladder cancer or other cancers from which the patient has been disease-free for at least 2 years
Active HIV, hepatitis B and hepatitis C or any clinically significant history of liver disease. Hepatitis B prior infection is not a contraindication though will require therapy.
Known hypersensitivity to any of the study drugs
Patients with HCL that are BRAF V600E mutation negative

Sites / Locations

Scripps MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Low dose Vemurafenib and Rituximab

Arm Description

Eligible patients will receive vemurafenib at a dose of 240 mg orally twice daily (b.i.d.) continuously for 8 weeks. Rituximab 375 mg/m2 will be administered every 2 weeks for a total of 16 weeks. The entire duration of treatment will be 16 weeks.

Outcomes

Primary Outcome Measures

Complete Response

Resolution of cytopenias and splenomegaly

Secondary Outcome Measures

Time to hematologic response

Days until resolution of cytopenias

MRD Status

At the time of bone marrow assessment by testing for BRAFV600E mutation status

Relapse-Free Survival

Reapperance of Hairy-Cell related cytopenia

Full Information

NCT ID

NCT05388123

First Posted

May 16, 2022

Last Updated

May 19, 2022

Sponsor

Scripps Health

1. Study Identification

Unique Protocol Identification Number

NCT05388123

Brief Title

Low Dose Vemurafenib and Rituximab in Hairy Cell Leukemia

Official Title

A Single Arm Phase II Pilot Study of Low Dose Vemurafenib Plus Rituximab in the Front-line and Relapsed/Refractory Treatment of Hairy Cell Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Recruiting

Study Start Date

January 1, 2022 (Actual)

Primary Completion Date

January 1, 2025 (Anticipated)

Study Completion Date

January 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Scripps Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The current standard-of-care for Hairy Cell Leukemia involves chemotherapy, with agents such as cladribine or pentostatin. Chemotherapy is associated with infection, low blood counts and predisposition to future cancers. This study tests a new drug combination for the treatment of hairy cell leukemia. The treatment involves 8 weeks of treatment with an oral drug called vemurafenib and 8 doses of an intravenous medication called rituximab. The goal of this study is to see whether this treatment is better tolerated and more effective than the currently used treatment in this disease. In addition, this study uses a lower dose of vemurafenib than previous studies have used, with the goal of minimizing side effects from this medication.

Detailed Description

This is a single-center, open label, single arm, investigator-initiated phase II trial of the oral BRAF inhibitor, vemurafenib, plus rituximab in patients with previously untreated or relapsed and refractory HCL. Eligible patients will receive vemurafenib at a dose of 240 mg orally twice daily (b.i.d.) continuously for 8 weeks. Rituximab 375 mg/m2 will be administered concomitantly with vemurafenib every 2 weeks from the first day of treatment. After completion of vemurafenib, the patient will receive rituximab 375 mg/m2 every 2 weeks for a total of 8 weeks. The entire duration of treatment will be 16 weeks. Six months after the initiation of the treatment, a peripheral blood flow cytometry and a bone marrow aspirate and biopsy will be performed for assessment of response and evaluation of minimal residual disease (MRD).

6. Conditions and Keywords

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

Hairy Cell Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Low dose Vemurafenib and Rituximab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Low dose vemurafenib plus rituximab

Other Intervention Name(s)

Vemurafenib, Rituximab

Intervention Description

Vemurafenib 960 mg twice daily for 8 weeks with concurrent rituximab 375 mg/m2 every 2 weeks followed by maintenance consolidative rituximab 4 times every 2 weeks post-vemurafenib

Primary Outcome Measure Information:

Title

Complete Response

Description

Resolution of cytopenias and splenomegaly

Time Frame

Up to 2 years from enrollment

Secondary Outcome Measure Information:

Title

Time to hematologic response

Description

Days until resolution of cytopenias

Time Frame

Up to 2 years from enrollment

Title

MRD Status

Description

At the time of bone marrow assessment by testing for BRAFV600E mutation status

Time Frame

At 6 months, 1 year and 2 years from treatment

Title

Relapse-Free Survival

Description

Reapperance of Hairy-Cell related cytopenia

Time Frame

From start of treatment until 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: ≥ 18 years of age Histologically confirmed HCL that are BRAF V600E positive by IHC or NGS Patient's must meet the standard treatment initiation criteria, as defined by ANC ≤1.0, Hgb ≤ 10.0 or PLT ≤100K Patients can either have (1) not received any prior therapy for the disease or have had (2) failure to achieve any response to the initial purine analog-based therapy or (3) subsequent relapse after any prior therapy. ECOG performance status of 0-2 Acceptable pre-study organ function during screening not exacerbated by Hairy Cell Leukemia. General thresholds should be a total bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN, and serum creatinine ≤ 1.5x ULN For women of childbearing potential, agreement to use acceptable methods of contraception For men with female partners of childbearing potential, agreement to use barrier contraception Negative serum pregnancy test within 7 days of commencement of treatment in premenopausal women. Ability to understand and willingness to sign a written informed consent document. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Exclusion Criteria: Pregnant or breast-feeding or intending to become pregnant during the study Have had chemotherapy (including purine analogs), rituximab, and other investigational agents within six weeks prior to entering the study. The patients cannot have received BRAF inhibitor therapy within 6 months of entering the study. Major surgery within 4 weeks prior to entering the study Invasive malignancy within the past 2 years prior to first study drug administration, except for adequately treated (with curative intent) basal or squamous cell carcinoma, melanoma, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, or limited stage bladder cancer or other cancers from which the patient has been disease-free for at least 2 years Active HIV, hepatitis B and hepatitis C or any clinically significant history of liver disease. Hepatitis B prior infection is not a contraindication though will require therapy. Known hypersensitivity to any of the study drugs Patients with HCL that are BRAF V600E mutation negative

Central Contact Person:

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

Alan Saven, MD

Phone

8585548788

saven.alan@scrippshealth.org

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

David J Hermel, MD

Phone

8585377617

hermel.david@scrippshealth.org

Facility Information:

Facility Name

Scripps MD Anderson Cancer Center

City

La Jolla

State/Province

California

ZIP/Postal Code

92037

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David J Hermel, MD

Phone

858-537-7617

hermel.david@scrippshealth.org

First Name & Middle Initial & Last Name & Degree

Alan Saven, MD

First Name & Middle Initial & Last Name & Degree

David Hermel, MD

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Plan to publish aggregate data in manuscript

Citations:

PubMed Identifier

33979489

Citation

Tiacci E, De Carolis L, Simonetti E, Capponi M, Ambrosetti A, Lucia E, Antolino A, Pulsoni A, Ferrari S, Zinzani PL, Ascani S, Perriello VM, Rigacci L, Gaidano G, Della Seta R, Frattarelli N, Falcucci P, Foa R, Visani G, Zaja F, Falini B. Vemurafenib plus Rituximab in Refractory or Relapsed Hairy-Cell Leukemia. N Engl J Med. 2021 May 13;384(19):1810-1823. doi: 10.1056/NEJMoa2031298.

Results Reference

background

PubMed Identifier

33947938

Citation

Grever M, Andritsos L, Banerji V, Barrientos JC, Bhat S, Blachly JS, Call T, Cross M, Dearden C, Demeter J, Dietrich S, Falini B, Forconi F, Gladstone DE, Gozzetti A, Iyengar S, Johnston JB, Juliusson G, Kraut E, Kreitman RJ, Lauria F, Lozanski G, Parikh SA, Park J, Polliack A, Ravandi F, Robak T, Rogers KA, Saven A, Seymour JF, Tadmor T, Tallman MS, Tam CS, Tiacci E, Troussard X, Zent C, Zenz T, Zinzani PL, Wormann B. Hairy cell leukemia and COVID-19 adaptation of treatment guidelines. Leukemia. 2021 Jul;35(7):1864-1872. doi: 10.1038/s41375-021-01257-7. Epub 2021 May 4.

Results Reference

background

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Low Dose Vemurafenib and Rituximab in Hairy Cell Leukemia

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