Clinical trial NCT00003991: Interleukin-2 Plus Histamine Dihydrochloride in Treating Patients With Acute Myeloid Leukemia
Official title: Multi-Center, Randomized Open-Label Study to Evaluate the Safety and Efficacy of Immunotherapy With Subcutaneous Maxamine (Histamine Dihydrochloride) Plus Proleukin (Interleukin-2) Versus No Treatment (Standard of Care) in Patients With Acute Myeloid Leukemia in First or Subsequent Complete Remission (CR)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Leukemia
Keywords: adult acute myeloid leukemia in remission
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-06-03
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Interleukin-2 may stimulate a person's white blood cells to kill acute myeloid leukemia cells. Histamine dihydrochloride may prolong remission and reduce the risk of relapse in patients with acute myeloid leukemia in remission.

PURPOSE: Randomized phase III trial to determine the effectiveness of interleukin-2 plus histamine dihydrochloride in treating patients who have acute myeloid leukemia that is in remission following previous therapy.

Detailed description: OBJECTIVES: I. Compare the efficacy of interleukin-2 plus histamine dihydrochloride (Maxamine) vs no further therapy in prolonging the leukemia free survival in patients with acute myeloid leukemia in first or subsequent complete remission (CR) following consolidation therapy. II. Compare the relapse rate, overall survival, and quality of life in this patient population treated with interleukin-2 plus Maxamine vs no further therapy. III. Compare the remission inversion rate in patients in subsequent CR with this treatment regimen vs no further therapy.

OUTLINE: This is a randomized, open label, parallel, multicenter study. Patients are stratified according to complete remission (first vs subsequent). Patients are randomized to one of two treatment arms. Arm I: Following consolidation chemotherapy or autologous stem cell transplantation, patients receive interleukin-2 subcutaneously followed by histamine dihydrochloride subcutaneously over 5-7 minutes twice daily on days 1-21. Treatment repeats every 6 weeks for 3 courses and then every 9 weeks for 7 courses in the absence of disease relapse or unacceptable toxicity. Arm II: Patients receive no further therapy following consolidation chemotherapy or autologous stem cell transplantation. Quality of life is assessed prior to study, and at visits 6, 7, 10, 11, 16, 17, and 22. Patients are followed for relapse and survival every 3 months for 2.5 years.

PROJECTED ACCRUAL: A total of 360 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Cytologically confirmed acute myeloid leukemia (AML) in first complete remission (CR) or subsequent CR Less than 5% blasts in normal bone marrow Less than 3 months since last dose of chemotherapy OR Less than 6 months since achieving CR

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: WHO 0-1 OR Karnofsky 70-100% Life expectancy: Greater than 3 months Hematopoietic: WBC at least 1,500/mm3 Platelet count at least 75,000/mm3 Hepatic: PTT normal Bilirubin no greater than 2 times upper limit of normal (ULN) SGOT and SGPT no greater than 2 times ULN Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No class III or IV heart disease No hypotension, severe hypertension, or serious or uncontrolled cardiac dysrhythmia (e.g., ventricular arrhythmias) No acute myocardial infarction within the past 12 months No active uncontrolled angina pectoris No symptomatic arteriosclerotic blood vessel disease Pulmonary: No history of asthma within the past 5 years Other: No other active malignancies except localized basal or squamous cell skin cancer or carcinoma in situ of the cervix HIV negative No prior or active peptic or esophageal ulcer disease No history of hypersensitivity to histamine or histamine products, or severe allergies Not pregnant or nursing

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior autologous stem cell transplantation allowed No prior allogeneic stem cell transplantation No other concurrent immunomodulating agents Chemotherapy: See Disease Characteristics Prior induction or consolidation therapy allowed No concurrent chemotherapy Endocrine therapy: At least 24 hours since prior corticosteroids No concurrent steroids Radiotherapy: Not specified Surgery: Not specified Other: No concurrent alternative therapy (e.g., laetrile, Brudzinski's treatment, etc.)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: Kaiser Permanente-Southern California Permanente Medical Group
state: California
city: San Diego
country: United States
facility: Sidney Kimmel Cancer Center
state: California
city: San Francisco
country: United States
facility: Pacific Hematology/Oncology
state: California
city: Boynton Beach
country: United States
facility: Bethesda Bone Marrow Stem Cell Transplant Institute
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Science Center - Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Westwood
country: United States
facility: Oncology and Hematology Associates
state: Kansas
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders
state: Maine
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Southfield
country: United States
facility: Providence Hospital Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Cancer Center
state: Nevada
city: Reno
country: United States
facility: Nevada Medical Group-Internal Medicine
state: Nevada
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Research & Treatment Center
state: New Mexico
city: Bronx
country: United States
facility: Our Lady of Mercy Medical Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Cornell Campus
state: New York
city: Rochester
country: United States
facility: University of Rochester Cancer Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Memphis
country: United States
facility: West Clinic, P.C.
state: Tennessee
city: Memphis
country: United States
facility: Boston Cancer Group
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Institute of South Texas
state: Texas
city: San Antonio
country: United States
facility: South Texas Cancer Institute
state: Texas
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: Newcastle Mater Misericordiae Hospital
state: New South Wales
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Westmead
country: Australia
facility: NSW Breast Cancer Institute
state: New South Wales
city: Auchenflower
country: Australia
facility: Wesley Clinic for Hematology/Oncology
state: Queensland
city: Brisbane
country: Australia
facility: Royal Brisbane Hospital
state: Queensland
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Public Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Hanson Center for Cancer Research
state: South Australia
city: Adelaide
country: Australia
facility: Queen Elizabeth Hospital
state: South Australia
city: East Bentleigh
country: Australia
facility: Monash Medical Center
state: Victoria
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Institute
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Fremantle
country: Australia
facility: Fremantle Hospital
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Science Center
state: Nova Scotia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Center - General Division
state: Ontario
city: Montreal
country: Canada
facility: Seaforth Medical Centre
state: Quebec
city: Montreal
country: Canada
facility: Hopital Du Sacre-Coeur de Montreal
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec, Pavillion de Quebec
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Aalborg
country: Denmark
facility: Aalborg Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Tallinn
country: Estonia
facility: Tallinn Central Hospital
city: Tartu
country: Estonia
facility: University of Tartu
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Central Hospital
city: Angers
country: France
facility: Centre Hospitalier Regional et Universitaire d'Angers
city: Besancon
country: France
facility: CHR de Besancon - Hopital Jean Minjoz
city: Clichy
country: France
facility: Hopital Beaujon
city: Le Chesnay
country: France
facility: Hopital Andre Mignot
city: Lille
country: France
facility: Centre Hospitalier Regional de Lille
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Nantes
country: France
facility: CHR Hotel Dieu
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Augsburg
country: Germany
facility: Zentralklinikum Augsburg
city: Berlin
country: Germany
facility: Universitaetsklinikum Charite
city: Bremen
country: Germany
facility: Evang. Diakonissenanstalt
city: Dresden
country: Germany
facility: Medizinische Klinik I
city: Essen
country: Germany
facility: Universitaetsklinik und Strahlenklinik - Essen
city: Frankfurt
country: Germany
facility: Klinikum der J.W. Goethe Universitaet
city: Halle Saale
country: Germany
facility: Martin Luther Universitaet
city: Hamburg
country: Germany
facility: Universitats-Krankenhaus Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Medizinische Klinik und Poliklinik
city: Osnabruck
country: Germany
facility: Staedtische Kliniken Osnabruek
city: Rostock
country: Germany
facility: Universitat Rostock
city: Saarbrucken
country: Germany
facility: Caritasklinik St. Theresa
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Ulm
country: Germany
facility: Klinikum der Universitaet Ulm
city: Wurzburg
country: Germany
facility: Medizinische Poliklinik der Universitat
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Petach-Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Hospital
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Medical Center-Ichilov Hospital
city: Auckland
country: New Zealand
facility: University of Auckland School of Medicine
city: Christchurch
country: New Zealand
facility: Canterbury Health Laboratories
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Palmerston North
country: New Zealand
facility: Palmerston North Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: Eskilstuna
country: Sweden
facility: County Hospital (Malar Hospital)
city: Gothenburg (Goteborg)
country: Sweden
facility: Sahlgrenska University Hospital
city: Kalmar
country: Sweden
facility: County Hospital/Kalmar
city: Karlstad
country: Sweden
facility: Central Hospital
city: Linkoping
country: Sweden
facility: University Hospital of Linkoping
city: Lund
country: Sweden
facility: Lund University Hospital
city: Malmo
country: Sweden
facility: Malmo University Hospital
city: Orebro
country: Sweden
facility: Regional Hospital
city: Skovde
country: Sweden
facility: County Hospital (Karnsjukhuset)
city: Stockholm
country: Sweden
facility: Huddinge Hospital
city: Stockholm
country: Sweden
facility: Karolinska Hospital
city: Sundsvall
country: Sweden
facility: County Hospital/Sundsvall
city: Uddevalla
country: Sweden
facility: County Hospital/Uddevalla
city: Umea
country: Sweden
facility: Umea Universitet
city: Uppsala
country: Sweden
facility: University Hospital - Uppsala
city: Vasteras
country: Sweden
facility: County Hospital/Vasteras
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands and Solihull NHS Trust (Teaching)
state: England
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospital Trust
state: England
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
state: England
Study officials:
affiliation: Maxim Pharmaceuticals
name: Barbara Berryhill
role: STUDY_CHAIR
References:
citation: Buyse M, Michiels S, Squifflet P, Lucchesi KJ, Hellstrand K, Brune ML, Castaigne S, Rowe JM. Leukemia-free survival as a surrogate end point for overall survival in the evaluation of maintenance therapy for patients with acute myeloid leukemia in complete remission. Haematologica. 2011 Aug;96(8):1106-12. doi: 10.3324/haematol.2010.039131. Epub 2011 May 5.
citation: Buyse M, Squifflet P, Lucchesi KJ, Brune ML, Castaigne S, Rowe JM. Assessment of the consistency and robustness of results from a multicenter trial of remission maintenance therapy for acute myeloid leukemia. Trials. 2011 Mar 23;12:86. doi: 10.1186/1745-6215-12-86.