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

NCT02092324 | Completed Phase 2 Results DMC

• 2 other identifiers: IRB00010262NCI-2014-00633
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 7

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Percentage of First 25 Enrolled Patients With a Hematologic Response to Ruxolitinib (Complete Response (CR), Partial Response (PR))

  A subject is defined as being responsive (responder) if he or she has achieved complete response (CR) or partial response (PR) at the beginning of cycle 7 compared to start of study (day 1,cycle 1). Subjects who do not reach the start of cycle 7 are counted as non-responders. Proportions with 95% exact confidence intervals will be computed. Protocol-defined Response evaluates changes in white blood cell count, absolute neutrophil count, marrow findings and spleen size to define response (attached protocol, Section 10.6, Clinical Response, Table 6 and Table). IWG-defined Response evaluates bone marrow cellularity and myeloblast percent, absence of osteopmyelofibrosis, peripheral blood elements (white blood cell, Neutrophil, Monocyte and platelet counts, hemoglobin density, percent blasts and Neutrophil precursors), symptom resolution, dysplasia, and spleen size to determine response (attached reference).

  Start of cycle 7

Secondary Outcomes (13)

• Percentage of Participant With Any Hematologic Grade III or IV Adverse Events.

  Up to 6 weeks after last dose of ruxolitinib phosphate

• Percentage of Participants With Any Non-hematologic Grade III or IV Adverse Events.

  Up to 6 weeks after last dose of ruxolitinib phosphate

• Percentage of Participants Who Achieved Clinical Response of Partial Response or Better

  Start of cycle 7

• Median Time on Study (Months) for Early Drop Offs

  End of cycle 6

• Median Time on Study (Months) for All Enrolled Subjects

  Outcome is measured from the first dose of study drug. If study drug continues to be effective, patient may be eligible to continue on study drug past 24 cycles (up to 4.5 years)

Study Arms (1)

Treatment (ruxolitinib phosphate)

EXPERIMENTAL

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.

Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Ruxolitinib Phosphate

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ruxolitinib phosphate)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (ruxolitinib phosphate)

Questionnaire Administration OTHER

Ancillary studies

Treatment (ruxolitinib phosphate)

Ruxolitinib Phosphate DRUG

Given PO

Also known as: INCB-18424 Phosphate, Jakafi

Treatment (ruxolitinib phosphate)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead

Study Sites (7)

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (3)

• 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.

  PMID: 25624319 BACKGROUND

• 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.

  PMID: 31880950 RESULT

• 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.

  PMID: 25180155 DERIVED

Related Links

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

MeSH Terms

Conditions

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

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myeloproliferative Disorders

Results Point of Contact

• Title: Dr. Kim-Hien Dao
• Organization: OHSU

daok@ohsu.edu

503-494-5074

Study Officials

• Kim-Hien Dao

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 18, 2014
• First Posted: March 20, 2014
• Study Start: July 8, 2014
• Primary Completion: November 22, 2019
• Study Completion: January 24, 2020
• Last Updated: November 16, 2020
• Results First Posted: November 16, 2020

Record last verified: 2020-10

Locations

US (7)