A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Hematologic Malignancies

NCT00109707 | Completed Phase 1 Results

• 1 other identifier: CAMN107A2101
• Study Type: interventional
• Target: 507
• Locations: 21 countries
• Sites: 98

Brief Summary

The purpose of this trial is to assess the efficacy, safety, tolerability, biologic activity, and pharmacokinetics of AMN107 in six groups of patients with one of the following conditions: Relapsed/refractory Ph+ Acute lymphoblastic leukemia (ALL) (arm 1) Group A - Imatinib failure only (arms 2, 3 and 4)

• imatinib-resistant or intolerant CML - Chronic Phase (CP)
• imatinib-resistant or intolerant CML - Accelerated Phase (AP)
• imatinib-resistant or intolerant CML - Blast Crisis (BC) Group B - Imatinib and other TKI failure (arms 2, 3 and 4)
• imatinib-resistant or intolerant CML - Chronic Phase (CP)
• imatinib-resistant or intolerant CML - Accelerated Phase (AP)
• imatinib-resistant or intolerant CML - Blast Crisis (BC) Hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL) (arm 5) Systemic mastocytosis (Sm) (arm 6)

Conditions

Chronic Myelogenous Leukemia; Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive); Hypereosinophilic Syndrome; Systemic Mastocytosis

Keywords

CML in blast crisis; CML in chronic phase; CML in accelerated phase; Gleevec resistance; Gleevec intolerant; Gleevec and CML; imatinib resistance; imatinib intolerant; Hypereosinophilic Syndrome; Systemic Mastocytosis; Chronic eosinophilic syndrome; Philadelphia chromosome positive acute lymphoblastic leukemia; HES; CEL; CML; SM; Ph+ ALL refractory to standard therapy; Ph+ALL relapsed; AMN107A

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Major Cytogenetic Response (MCyR)

  Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in bone marrow) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in bone marrow).

  Up to End of the Treatment (Approximately 7.5 years)

• Number of Participants Confirmed Overall Hematological Response (Phase II)

  Hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count \<10 x 109/L, Platelet count \<450 x 109/L, Basophils \<5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes \< 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver). Hematological response was a primary outcome measure for Arm CML-AP with prior imatinib only.

  Up to End of the Treatment (Approximately 7.5 years)

Secondary Outcomes (6)

• Number of Participants With Overall Major Cytogenetic Responses (Phase II)

  Up to End of the Treatment (Approximately 7.5 years)

• Number of Participants With Complete Hematologic Response (Phase II)

  Up to End of the Treatment (Approximately 7.5 years)

• Participants With (MMR) Major Molecular Response (Phase II)

  Up to End of the Treatment (Approximately 7.5 years)

• Time to Progression (TTP) (Phase II)

  Up to End of the Treatment (Approximately 7.5 years)

• Overall Survival (OS) (Phase II)

  Up to End of the Treatment (Approximately 7.5 years)

Study Arms (3)

CML-CP With Prior Imatinib Only

EXPERIMENTAL

Imatinib-resistant / intolerant PH+ CML-CP patients

Drug: Nilotinib

CML-AP With Prior Imatinib Onl

EXPERIMENTAL

Imatinib-resistant / intolerant PH+ CML-AP patients

Drug: Nilotinib

CML-CP

EXPERIMENTAL

Imatinib-resistant / intolerant PH+ CML-CP patients

Drug: Nilotinib

Interventions

Nilotinib DRUG

CML-AP With Prior Imatinib Onl; CML-CP; CML-CP With Prior Imatinib Only

Eligibility Criteria

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

You may qualify if:

• Patients with CML in blast crisis, CML in accelerated phase defined as never in blast crisis phase, or CML in chronic phase defined as never been in blast crisis phase or accelerated phase who have: \*developed progressive disease during therapy with at least 600 mg of imatinib per day, -OR- \*patients with CML on imatinib therapy, at any dose, developing progressive disease and the presence of a genetic mutation likely to result in imatinib resistance -OR- \*have developed an intolerance to imatinib
• Relapsed or refractory Ph+ ALL
• Hypereosinophilic syndrome/chronic eosinophilic leukemia.
• Systemic mastocytosis who have a clinical indication for treatment.
• Prior imatinib therapy for patients with Ph+ ALL, HES/CEL and SM is permitted but is not required
• CML patients who have been treated with an investigational tyrosine kinase inhibitor who otherwise meet the definition of imatinib-resistance or intolerance are eligible
• Written informed consent prior to any study procedures being performed

You may not qualify if:

• Impaired cardiac function
• Patients with severe/chronic or uncontrolled medical conditions (including but not limited to diabetes, infections, GI impairment, CNS infiltration, liver and kidney disease)
• Prior and concomitant use of certain medications (including but not limited to warfarin, chemotherapy, hematopoietic colony-stimulating growth factors, medications that can affect electrocardiogram test results, other investigational drugs )
• Women who are pregnant or breastfeeding
• Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
• Patients unwilling to comply with the protocol.
• Known diagnosis of human immunodeficiency virus (HIV) infection

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (101)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Stanford University Medical Center

Stanford, California, 94305-5750, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

H. Lee Moffitt Cancer Center & Research Institute Dept.of H. Lee Moffitt

Tampa, Florida, 33612, United States

Location

University of Chicago Medical Center Dept. of U. of Chicago Hosp(3)

Chicago, Illinois, 60637, United States

Location

University of Illinois at Chicago Divisionof Hematology/Oncology

Chicago, Illinois, United States

Location

Indiana Blood and Marrow Institute Dept of Indiana Blood&Mar (2)

Beech Grove, Indiana, 46107, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Div.of Hematologic Malignancie

Baltimore, Maryland, 21231, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan Health System Clinical Trials Office

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

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Roswell Park Cancer Institute Rosewell SC

Buffalo, New York, 14263, United States

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Memorial Sloan Kettering Cancer Center

New York, New York, 10017, United States

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University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

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Oregon Health Sciences University

Portland, Oregon, 97239, United States

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The Jones Clinic

Germantown, Tennessee, 38138, United States

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Vanderbilt University Medical Center, Clinical Trials Center Investigational Drug Services

Nashville, Tennessee, 37212, United States

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MD Anderson Cancer Center/University of Texas

Houston, Texas, 77030, United States

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Swedish Cancer Institute

Seattle, Washington, 98104, United States

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Novartis Investigative Site

St Leonards, New South Wales, 2065, Australia

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Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

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Novartis Investigative Site

Prahran, Victoria, 3181, Australia

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Novartis Investigative Site

Vienna, A-1090, Austria

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Novartis Investigative Site

Brussels, 1000, Belgium

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Novartis Investigative Site

Haine-Saint-Paul, 7100, Belgium

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Novartis Investigative Site

Leuven, 3000, Belgium

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Novartis Investigative Site

Yvoir, 5530, Belgium

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Novartis Investigative Site

Vancouver, British Columbia, V5Z 4E3, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Montreal, Quebec, H3A 1A1, Canada

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Vejle, DK-7100, Denmark

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HUS Helsinki, FIN-00029, Finland

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Bordeaux, 33076, France

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Novartis Investigative Site

Créteil, 94010, France

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Novartis Investigative Site

Dijon, 21034, France

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Novartis Investigative Site

Lille, 59037, France

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Novartis Investigative Site

Limoges, 87042, France

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Lyon, 69437, France

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Marseille, 13273, France

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Poitiers, 86021, France

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Rennes, 35019, France

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Novartis Investigative Site

Vandœuvre-lès-Nancy, 54511, France

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Berlin, 13353, Germany

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Novartis Investigative Site

Düsseldorf, 40225, Germany

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Novartis Investigative Site

Frankfurt/M, 60590, Germany

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Hamburg, 20246, Germany

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Leipzig, 04103, Germany

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Novartis Investigative Site

Mainz, 55131, Germany

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Mannheim, 68169, Germany

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München, 81675, Germany

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Pokfulam, Hong Kong, Hong Kong

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Bergamo, BG, 24128, Italy

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Bologna, BO, 40138, Italy

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Novartis Investigative Site

Genova, GE, 16132, Italy

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Monza, MB, 20900, Italy

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Milan, MI, 20162, Italy

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Pescara, PE, 65124, Italy

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Pavia, PV, 27100, Italy

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Reggio Calabria, RC, 89124, Italy

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Novartis Investigative Site

Roma, RM, 00144, Italy

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Novartis Investigative Site

Roma, RM, 00161, Italy

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Novartis Investigative Site

Roma, RM, 00168, Italy

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Novartis Investigative Site

Orbassano, TO, 10043, Italy

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Napoli, 80131, Italy

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Amsterdam, 1081 HV, Netherlands

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Rotterdam, Netherlands

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Grafton, Auckland, New Zealand

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Oslo, NO-0310, Norway

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Katowice, 40-635, Poland

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Novartis Investigative Site

Lodz, 90-153, Poland

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Novartis Investigative Site

Warsaw, 02-097, Poland

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Novartis Investigative Site

Warsaw, 02-776, Poland

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Novartis Investigative Site

Wroclaw, 50-367, Poland

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Novartis Investigative Site

Singapore, 169608, Singapore

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Novartis Investigative Site

Hwasun-gun, Jeollanam-do, 519-809, South Korea

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Novartis Investigative Site

Seoul, Korea, 05505, South Korea

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Novartis Investigative Site

Seoul, Korea, 137-701, South Korea

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Novartis Investigative Site

Taegu, 700 - 721, South Korea

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Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

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Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

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Gothenburg, SE-413 45, Sweden

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Novartis Investigative Site

Linköping, SE-581 85, Sweden

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Novartis Investigative Site

Lund, SE-221 85, Sweden

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Novartis Investigative Site

Uppsala, SE-751 85, Sweden

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Basel, 4031, Switzerland

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Geneva, 1211, Switzerland

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Niaosong Township, Taiwan, 83301, Taiwan

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Birmingham, B15 2TH, United Kingdom

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Novartis Investigative Site

Cambridge, CB2 2QQ, United Kingdom

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Novartis Investigative Site

Glasgow - Scotland, G12 OYN, United Kingdom

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Novartis Investigative Site

Leeds, LS9 7TF, United Kingdom

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Liverpool, L7 8XP, United Kingdom

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Novartis Investigative Site

London, SE5 9RS, United Kingdom

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Novartis Investigative Site

London, W12 0NN, United Kingdom

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Novartis Investigative Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

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Related Publications (6)

• Hochhaus A, Baccarani M, Giles FJ, le Coutre PD, Muller MC, Reiter A, Santanastasio H, Leung M, Novick S, Kantarjian HM. Nilotinib in patients with systemic mastocytosis: analysis of the phase 2, open-label, single-arm nilotinib registration study. J Cancer Res Clin Oncol. 2015 Nov;141(11):2047-60. doi: 10.1007/s00432-015-1988-0. Epub 2015 May 23.

  PMID: 26002753 DERIVED

• Hochhaus A, le Coutre PD, Kantarjian HM, Baccarani M, Erben P, Reiter A, McCulloch T, Fan X, Novick S, Giles FJ. Effect of the tyrosine kinase inhibitor nilotinib in patients with hypereosinophilic syndrome/chronic eosinophilic leukemia: analysis of the phase 2, open-label, single-arm A2101 study. J Cancer Res Clin Oncol. 2013 Dec;139(12):1985-93. doi: 10.1007/s00432-013-1529-7. Epub 2013 Sep 22.

  PMID: 24057647 DERIVED

• Stein AM, Martinelli G, Hughes TP, Muller MC, Beppu L, Gottardi E, Branford S, Soverini S, Woodman RC, Hochhaus A, Kim DW, Saglio G, Radich JP. Rapid initial decline in BCR-ABL1 is associated with superior responses to second-line nilotinib in patients with chronic-phase chronic myeloid leukemia. BMC Cancer. 2013 Apr 2;13:173. doi: 10.1186/1471-2407-13-173.

  PMID: 23547655 DERIVED

• Kantarjian HM, Giles FJ, Bhalla KN, Pinilla-Ibarz J, Larson RA, Gattermann N, Ottmann OG, Hochhaus A, Radich JP, Saglio G, Hughes TP, Martinelli G, Kim DW, Shou Y, Gallagher NJ, Blakesley R, Baccarani M, Cortes J, le Coutre PD. Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results. Blood. 2011 Jan 27;117(4):1141-5. doi: 10.1182/blood-2010-03-277152. Epub 2010 Nov 22.

  PMID: 21098399 DERIVED

• Kantarjian HM, Giles F, Gattermann N, Bhalla K, Alimena G, Palandri F, Ossenkoppele GJ, Nicolini FE, O'Brien SG, Litzow M, Bhatia R, Cervantes F, Haque A, Shou Y, Resta DJ, Weitzman A, Hochhaus A, le Coutre P. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood. 2007 Nov 15;110(10):3540-6. doi: 10.1182/blood-2007-03-080689. Epub 2007 Aug 22.

  PMID: 17715389 DERIVED

• Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006 Jun 15;354(24):2542-51. doi: 10.1056/NEJMoa055104.

  PMID: 16775235 DERIVED

Related Links

• Results for CAMN107A2101 on the Novartis Clinical Trials Website

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hypereosinophilic Syndrome; Mastocytosis, Systemic

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Eosinophilia; Leukocyte Disorders; Mastocytosis; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Mast Cell Activation Disorders

Results Point of Contact

• Title: Study Director
• Organization: NovartisPharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticlas

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2005
• First Posted: May 3, 2005
• Study Start: April 1, 2005
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: June 29, 2021
• Results First Posted: June 29, 2021

Record last verified: 2021-06

Locations

AU (1); FI (1); BE (4); HK (1); NO (1); PL (5); SG (1); FR (10); KR (4); CA (4); ES (2); NZ (1); DK (1); CH (2); GB (8); TW (1); DE (8); IT (13); NL (2); SE (4); US (24)