Ruxolitinib Phosphate in Treating Patients With Chronic Neutrophilic Leukemia or Atypical Chronic Myeloid Leukemia

NCT ID: NCT02092324

Last Updated: 2020-11-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-08
• Study Completion Date: 2020-01-24

Brief Summary

This phase II trial studies how well ruxolitinib phosphate works in treating patients with chronic neutrophilic leukemia (CNL) or atypical chronic myeloid leukemia (aCML). Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cells to reproduce. This trial also studies the genetic makeup of patients. Certain genes in cancer cells may determine how the cancer grows or spreads and how it may respond to different drugs. Studying how the genes associated with CNL and aCML respond to the study drug may help doctors learn more about CNL and aCML and improve the treatment for these diseases.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the proportion of patients with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) who have a hematologic response to ruxolitinib (ruxolitinib phosphate) (partial response [PR], complete response [CR], complete response, partial [CRp]).

SECONDARY OBJECTIVES:

I. To determine the frequency of grade 3 or 4 hematologic and non-hematologic adverse events experienced by subjects during therapy with ruxolitinib.

II. To determine whether hematologic responses correlate with certain types of mutations in colony stimulating factor 3 receptor (CSF3R) and reduction in mutant CSF3R allele burden in the peripheral blood.

III. To determine the maximum clinical responses for each subject and the median duration of maximum clinical responses.

IV. To determine the mean % reduction of spleen size, estimated by volume using the conventional prolate ellipsoid method as measured by ultrasound compare to baseline.

V. To determine the mean % reduction of total symptom score as measured by a modified Myeloproliferative Neoplasm Symptom Assessment Form version 2.0 (MPN-SAF) compared to start of study (day 1, cycle 1).

VI. To determine overall survival in subjects who complete a minimum of 1 dose of study drug.

VII. To determine the proportion of subjects who discontinue after completion of > 3 cycles but < 6 cycles.

VIII. To determine the proportion of subjects who discontinue prior to completion of cycle 3.

OUTLINE:

Patients receive ruxolitinib phosphate orally (PO) every other day, once daily (QD), or twice daily (BID) on days 1-28. Each patient will be followed for a maximum of 96 weeks (24 cycles, 1 cycle is 4 weeks long). If the study drug continues to be effective, the patient may be eligible to continue on study drug past 24 cycles.

After completion of study treatment, patients are followed up within 2 weeks and at 4-6 weeks.

Conditions

Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Neutrophilic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (ruxolitinib phosphate)

Patients receive ruxolitinib phosphate PO every other day, QD, or BID on days 1-28. Each patient will be followed for a maximum of 96 weeks (24 cycles, 1 cycle is 4 weeks long). If the study drug continues to be effective, the patient may be eligible to continue on study drug past 24 cycles.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Quality-of-Life Assessment

Intervention Type: OTHER

Ancillary studies

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Ruxolitinib Phosphate

Intervention Type: DRUG

Given PO

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Quality-of-Life Assessment

Ancillary studies

Intervention Type: OTHER

Questionnaire Administration

Ancillary studies

Intervention Type: OTHER

Ruxolitinib Phosphate

Given PO

Intervention Type: DRUG

Other Intervention Names

Quality of Life Assessment; INCB-18424 Phosphate; Jakafi

Eligibility Criteria

Inclusion Criteria

• Subjects must be newly diagnosed or previously diagnosed with CNL or aCML; all patients must have a bone marrow biopsy completed during the screening or baseline period if one has not been done within 90 days of day 1, cycle one
• Subjects must have platelet count greater than 25,000 per microliter at baseline and at the start of study (day 1, cycle 1) visit
• Subjects must be able to discontinue any drug treatment aimed at lowering disease burden in CNL or aCML; subjects should discontinue hydroxyurea to treat underlying CNL or aCML disease no later than day -7 (one week before starting ruxolitinib); for drugs that have more long-lasting effects on the marrow, such as thalidomide and its analogs, and interferon, subjects should discontinue these no later than day -28
• Subjects must be willing to accept/continue transfusions to treat low hemoglobin levels
• Subjects must have a life expectancy of > 6 months

Exclusion Criteria

• Subjects unable to review and sign informed consent form
• Females who are pregnant or breastfeeding, and males and females who cannot comply with requirements to avoid fathering a child or becoming pregnant
• Subjects with known diagnosis of human immunodeficiency virus (HIV) or chronic active Hepatitis B or C; viral testing is not required; subjects with a history of Hepatitis B and/or C are allowed on trial if the virus is undetected at the time of enrollment
• Subjects with inadequate liver (alanine aminotransferase [ALT]/serum glutamate pyruvate transaminase [SGPT] above 4 X upper limit of normal [ULN] or direct bilirubin 4 X ULN AND the lab abnormalities are felt to be due to underlying liver dysfunction)
• Subjects with end stage renal function (creatinine clearance [CrCl] < 15 mL/min or glomerular filtration rate [GFR] <15 mL/min) regardless of whether hemodialysis is required
• Subjects with clinically serious infections requiring ongoing antibiotic therapy
• Subjects with severe (immediately life threatening) and recent (occurring within the last 3 months) cardiac dysfunction, pulmonary dysfunction, esophageal variceal bleeding, hemorrhagic strokes, or intracranial hemorrhage are not eligible for study participation
• Subjects requiring therapeutic doses of anticoagulation or anti-platelet therapies (aspirin above 81 mg daily, Plavix or similar agents) AND platelet counts are below 50,000 on two different laboratory evaluations, separated by minimum of two weeks
• Taking investigational or commercial agents or therapies with the intent to treat the subject's malignancy other than those therapies permitted
• Subjects with invasive malignancy over the previous 2 years except treated early stage carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix, and completely resected papillary thyroid and follicular thyroid cancers
• Previous allergic reactions to janus kinase (JAK) inhibitors or excipients
• Prior therapy with ruxolitinib or other JAK inhibitors
• Subjects who have had major surgery within 4 weeks prior to entering the study
• Subjects who are anticipated to receive a transplant within the first 6 months of treatment on trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

OHSU Knight Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Kim-Hien Dao

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kim-Hien Dao

Role: PRINCIPAL_INVESTIGATOR

OHSU Knight Cancer Institute

Locations

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Washington University School of Medicine

St Louis, Missouri, United States

OHSU Knight Cancer Institute

Portland, Oregon, United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

Savona MR, Malcovati L, Komrokji R, Tiu RV, Mughal TI, Orazi A, Kiladjian JJ, Padron E, Solary E, Tibes R, Itzykson R, Cazzola M, Mesa R, Maciejewski J, Fenaux P, Garcia-Manero G, Gerds A, Sanz G, Niemeyer CM, Cervantes F, Germing U, Cross NC, List AF; MDS/MPN International Working Group. An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults. Blood. 2015 Mar 19;125(12):1857-65. doi: 10.1182/blood-2014-10-607341. Epub 2015 Jan 26.

Reference Type: BACKGROUND

PMID: 25624319 (View on PubMed)

Dao KT, Gotlib J, Deininger MMN, Oh ST, Cortes JE, Collins RH Jr, Winton EF, Parker DR, Lee H, Reister A, Schultz, Savage S, Stevens, Brockett C, Subbiah N, Press RD, Raess PW, Cascio M, Dunlap J, Chen Y, Degnin C, Maxson JE, Tognon CE, Macey T, Druker BJ, Tyner JW. Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia. J Clin Oncol. 2020 Apr 1;38(10):1006-1018. doi: 10.1200/JCO.19.00895. Epub 2019 Dec 27.

Reference Type: RESULT

PMID: 31880950 (View on PubMed)

Dao KH, Solti MB, Maxson JE, Winton EF, Press RD, Druker BJ, Tyner JW. Significant clinical response to JAK1/2 inhibition in a patient with CSF3R-T618I-positive atypical chronic myeloid leukemia. Leuk Res Rep. 2014 Aug 1;3(2):67-9. doi: 10.1016/j.lrr.2014.07.002. eCollection 2014.

Reference Type: DERIVED

PMID: 25180155 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/25624319/

An international consortium proposal of uniform response criteria for myelodysplastic/myeloprolierative neoplasms (MDS/MPN) in adults

Other Identifiers

NCI-2014-00633

Identifier Type: REGISTRY

Identifier Source: secondary_id

IRB00010262

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00010262

Identifier Type: -

Identifier Source: org_study_id