The Role of Ruxolitinib in Secondary Acute Myelogenous Leukemia Evolving From Myeloproliferative Neoplasm

NCT03558607 | Unknown Phase 1

• 1 other identifier: H-1803-145-934
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

This trial aimed to investigate the therapeutic efficacy of ruxolitinib in combination with cytotoxic chemotherapy for post-myeloproliferative neoplasm secondary acute myeloid leukemia.

Conditions

Secondary Acute Myelogenous Leukemia Evolving From Myeloproliferative Disorder

Outcome Measures

Primary Outcomes (2)

• complete remission rate

  After 12 months from induction chemotherapy

• complete remission with incompletre recovery rate

  After 12 months from induction chemotherapy

Secondary Outcomes (3)

• Overall survival

  3, 6, 12, 24 months after induction chemotherapy

• Progression-free survival

  3, 6, 12, 24 months after induction chemotherapy

• Toxicity profile

  3, 6, 12, 24 months after induction chemotherapy

Study Arms (1)

Experimental arm

EXPERIMENTAL

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

Induction chemotherapy include combination of cytarabine (200mg/m2) and idarubicin (12mg/m2). Both 7+3 and 5+2 regimen is allowed according to age and performance status (PS) as follows; * If Age \< 55 years and ECOG PS \< 2 : 7+3 regimen * If Age ≥ 55 years or ECOG PS = 2 : 5+2 regimen Ruxolitinib is administered for 14 days during induction/consolidation phase. After complete remission after induction, ruxolitinib is administered for the first 14 days during consolidation chemotherapy. Maximum 3 cycles of consolidation is recommended. In case of allogeneic stem cell transplantation (alloSCT), ruxolitinib is discontinued at the time of transplantation. After completion of consolidation, 2 years of ruxolitinib maintenance is planned. The follow-up period is from the time of enrollment until 24 months.

Experimental arm

Eligibility Criteria

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

You may qualify if:

• Cytologically confirmed AML following MPN
• ECOG performance status 2 or better
• Adequate physical condition that could tolerate cytotoxic induction chemotherapy judged by investigator
• Age 18 years or older
• Adequate cardiac function
• Adequate hepatic, and renal function
• Serum creatinine ≤ 2.5 mg/dl
• ALT (SGOT) and/or AST (SGPT) equal to or than 1.5 x upper limit of normal
• Life expectancy of ≥ 3 months
• Signed and dated informed consent of document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment
• For women of childbearing age, it should be confirmed that they are not pregnant and that they should be contraception during the study period and for up to 4 weeks after the end of the study
• Male should agree to the barrier method during the study period and up to four weeks after the end of the study

You may not qualify if:

• Diagnosis of any serious secondary malignancy within the last 2 years, except for adequately treated basal cell or squamous cell carcinoma of skin, or in situ carcinoma of cervix uteri
• Pregnancy or breast feeding
• Other severe acute or chronic medical or psychiatric condition
• Prior treatment with ruxolitinib
• Patients who received other chemotherapy within 2 weeks of the study enrollment
• Patients participating in other clinical studies at the time of registration

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (2)

Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Related Publications (11)

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  PMID: 20587614 BACKGROUND

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  PMID: 15388582 BACKGROUND

• Passamonti F, Rumi E, Arcaini L, Castagnola C, Lunghi M, Bernasconi P, Giovanni Della Porta M, Columbo N, Pascutto C, Cazzola M, Lazzarino M. Leukemic transformation of polycythemia vera: a single center study of 23 patients. Cancer. 2005 Sep 1;104(5):1032-6. doi: 10.1002/cncr.21297.

  PMID: 16047334 BACKGROUND

• Tam CS, Nussenzveig RM, Popat U, Bueso-Ramos CE, Thomas DA, Cortes JA, Champlin RE, Ciurea SE, Manshouri T, Pierce SM, Kantarjian HM, Verstovsek S. The natural history and treatment outcome of blast phase BCR-ABL- myeloproliferative neoplasms. Blood. 2008 Sep 1;112(5):1628-37. doi: 10.1182/blood-2008-02-138230. Epub 2008 Jun 19.

  PMID: 18566326 BACKGROUND

• Cherington C, Slack JL, Leis J, Adams RH, Reeder CB, Mikhael JR, Camoriano J, Noel P, Fauble V, Betcher J, Higgins MS, Gillette-Kent G, Tremblay LD, Peterson ME, Olsen JJ, Tibes R, Mesa RA. Allogeneic stem cell transplantation for myeloproliferative neoplasm in blast phase. Leuk Res. 2012 Sep;36(9):1147-51. doi: 10.1016/j.leukres.2012.04.021. Epub 2012 May 11.

  PMID: 22578777 BACKGROUND

• Heaney ML, Soriano G. Acute myeloid leukemia following a myeloproliferative neoplasm: clinical characteristics, genetic features and effects of therapy. Curr Hematol Malig Rep. 2013 Jun;8(2):116-22. doi: 10.1007/s11899-013-0154-5.

  PMID: 23572311 BACKGROUND

• Abdel-Wahab O, Manshouri T, Patel J, Harris K, Yao J, Hedvat C, Heguy A, Bueso-Ramos C, Kantarjian H, Levine RL, Verstovsek S. Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias. Cancer Res. 2010 Jan 15;70(2):447-52. doi: 10.1158/0008-5472.CAN-09-3783. Epub 2010 Jan 12.

  PMID: 20068184 BACKGROUND

• Beer PA, Delhommeau F, LeCouedic JP, Dawson MA, Chen E, Bareford D, Kusec R, McMullin MF, Harrison CN, Vannucchi AM, Vainchenker W, Green AR. Two routes to leukemic transformation after a JAK2 mutation-positive myeloproliferative neoplasm. Blood. 2010 Apr 8;115(14):2891-900. doi: 10.1182/blood-2009-08-236596. Epub 2009 Dec 11.

  PMID: 20008300 BACKGROUND

• Eghtedar A, Verstovsek S, Estrov Z, Burger J, Cortes J, Bivins C, Faderl S, Ferrajoli A, Borthakur G, George S, Scherle PA, Newton RC, Kantarjian HM, Ravandi F. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. Blood. 2012 May 17;119(20):4614-8. doi: 10.1182/blood-2011-12-400051. Epub 2012 Mar 15.

  PMID: 22422826 BACKGROUND

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  PMID: 2702835 BACKGROUND

MeSH Terms

Interventions

ruxolitinib

Central Study Contacts

Youngil Koh, Dr.

CONTACT

+82-2-2072-3079; go01@snu.ac.kr

Ryul Kim, Dr.

CONTACT

+82 10 9412 6108; chrono0707@icloud.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: June 15, 2018
• Study Start: May 17, 2018
• Primary Completion: April 30, 2022
• Study Completion: August 31, 2024
• Last Updated: March 19, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (2)