Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

NCT00844298 | Completed Phase 2 Results

• 3 other identifiers: CDR0000632225AMC-UUCM-2008-0310NOVARTIS-AMC-UUCM-2008-0310
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 16

Brief Summary

RATIONALE: Nilotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving nilotinib together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving nilotinib together with combination chemotherapy works in treating patients with newly diagnosed acute lymphoblastic leukemia.

Conditions

Leukemia

Keywords

Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia; untreated adult acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Achieving Hematologic and Molecular Complete Remission (CR) After Induction Therapy

  approximate time: at the recovery of cytopenia

  1 month

Secondary Outcomes (2)

• Disease(Relapse)-Free Survival

  2 years

• Overall Survival

  2 years

Study Arms (1)

Nilotinib+mVPD

EXPERIMENTAL

Patients who were Philadelphia-positive, newly-diagnosed adult ALL and treated with nilotinib + mVPD treatment plan

Drug: Nilotinib+mVPD

Interventions

Nilotinib+mVPD DRUG

1. Induction: * Daunorubicin 90 mg/m2/day by continuous iv infusion (d1-3) * Vincristine 2 mg iv push (d1, 8, 15, 22) * Prednisolone 60 mg/m2/day po (d1-28) * Nilotinib 400mg bid/d (d8-) 2. Consolidation A (cycle1) * Daunorubicin 45 mg/m2/day by continuous iv (d1, 2) * Vincristine 2 mg iv (d1, 8) * Prednisolone 60 mg/m2/day po (d1-14) * Nilotinib 400mg bid/d 3. Consolidation B (cycles 2\&4) * Cytarabine 2,000 mg/m2/day iv over 2 hours (d1-4) * Etoposide 150 mg/m2/day iv over 3 hours (d1-4) * Nilotinib 400mg bid/d 4. Consolidation C (cycles 3\&5) * Methotrexate 220 mg/m2 iv bolus, then 60mg/m2/h for 36 hours (d1-2, 15-16) * Leucovorin followed immediately by 50 mg/m2 iv every 6hrs for three doses, * Nilotinib 400mg bid/d 5. Maintenance ◦Nilotinib 400mg bid/d (during 2 years, for patients without alloHCT) 6. Consider alloHCT

Also known as: Mabthera, VCS, Daunobrastina, Solondo, Leunase, Cytarabine, Efosin, DBLMethotrexate

Nilotinib+mVPD

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Newly diagnosed acute lymphoblastic leukemia or acute mixed lineage leukemia * Positive for Bcr-Abl fusion transcript (Philadelphia chromosome-positive disease) by RT-PCR PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Total bilirubin \< 2 mg/dL * SGOT \< 3 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN (unless considered tumor-related) * Creatinine \< 2.0 mg/dL ULN * Serum amylase and lipase ≤ 1.5 times ULN * Potassium, magnesium, and phosphorus normal (supplementation allowed) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No rare hereditary problems with galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption * No known sensitivity to any of the study drugs * No severe medical condition that, in the opinion of the investigator, would preclude study participation * No impaired cardiac function, including any of the following: * LVEF \< 45% or below the lower limit of normal by ECHO * Long QT syndrome or known family history of long QT syndrome * Clinically significant resting bradycardia (\< 50 beats per minute) * QTc \> 450 msec on baseline ECG (using the QTcF formula) * Myocardial infarction within the past 12 months * Other clinically significant heart disease, including any of the following: * Unstable angina * Congestive heart failure * Uncontrolled hypertension * Uncontrolled arrhythmias * No other primary malignant disease requiring systemic treatment * No acute or chronic liver, pancreatic, or severe renal disease * No other severe and/or life-threatening medical disease * No history of significant congenital or acquired bleeding disorder unrelated to cancer * No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug * No history of non-compliance PRIOR CONCURRENT THERAPY: * More than 30 days since prior investigational agents * No concurrent medications that have the potential to prolong the QTc interval * No concurrent strong CYP3A4 inhibitors * No concurrent therapeutic coumarin derivatives

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (16)

Daegu Fatima Hospital

Daegu, 701-600, South Korea

Location

Kyungpook National University Hospital

Daegu, 702-701, South Korea

Location

Yeungnam University Medical Center

Daegu, 712-749, South Korea

Location

Daegu Catholic University Hospital

Daegu, South Korea

Location

National Cancer Center - Korea

Goyang, 410-769, South Korea

Location

Chonnam National University Hwasun Hospital

Jeollanam-do, 519-809, South Korea

Location

Gyeongsang National University Hospital

Jinju, 660-701, South Korea

Location

Pusan National University Hospital

Pusan, 602-739, South Korea

Location

Inje University Seoul Paik Hospital

Seoul, 100-032, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Kyung Hee University Hospital

Seoul, 130-702, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Asan Medical Center - University of Ulsan College of Medicine

Seoul, 138-736, South Korea

Location

Konkuk University Medical Center

Seoul, 143-729, South Korea

Location

Ajou University Hospital

Suwon, 441-749, South Korea

Location

Ulsan University Hospital

Ulsan, South Korea

Location

Related Publications (1)

• Kim DY, Joo YD, Lim SN, Kim SD, Lee JH, Lee JH, Kim DH, Kim K, Jung CW, Kim I, Yoon SS, Park S, Ahn JS, Yang DH, Lee JJ, Lee HS, Kim YS, Mun YC, Kim H, Park JH, Moon JH, Sohn SK, Lee SM, Lee WS, Kim KH, Won JH, Hyun MS, Park J, Lee JH, Shin HJ, Chung JS, Lee H, Eom HS, Lee GW, Cho YU, Jang S, Park CJ, Chi HS, Lee KH; Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015 Aug 6;126(6):746-56. doi: 10.1182/blood-2015-03-636548. Epub 2015 Jun 11.

  PMID: 26065651 DERIVED

MeSH Terms

Conditions

Leukemia

Interventions

Rituximab; Asparaginase; Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

The limitation of the current study was that this study was not performed in a randomized comparative way, and the advantages of nilotinib over other TKIs were not definitely demonstrated.

Results Point of Contact

• Title: Dr. Dae-Young Kim
• Organization: Asan Medical Center, University of Ulsan College of Medicine

dani@amc.seoul.kr

82230105930

Study Officials

• Kyoo H. Lee, MD

  Asan Medical Center

  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: Professor

Study Record Dates

• First Submitted: February 13, 2009
• First Posted: February 16, 2009
• Study Start: January 1, 2009
• Primary Completion: June 1, 2012
• Study Completion: July 1, 2014
• Last Updated: September 7, 2015
• Results First Posted: September 7, 2015

Record last verified: 2015-08

Locations

KR (16)