Interleukin-2 Plus Histamine Dihydrochloride in Treating Patients With Acute Myeloid Leukemia

Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003991
• Other study ID #: CDR0000067196
• Secondary ID: MAXIM-MP-MA-0201
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: November 5, 2013
• Start date: July 1998
• Est. completion date: August 2011

Study information

• Verified date: December 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.)

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• aldesleukin

Drug:
• histamine dihydrochloride

Locations

Country	Name	City	State
Australia	Hanson Center for Cancer Research	Adelaide	South Australia
Australia	Queen Elizabeth Hospital	Adelaide	South Australia
Australia	Wesley Clinic for Hematology/Oncology	Auchenflower	Queensland
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Royal Brisbane Hospital	Brisbane	Queensland
Australia	Monash Medical Center	East Bentleigh	Victoria
Australia	Peter MacCallum Cancer Institute	East Melbourne	Victoria
Australia	Fremantle Hospital	Fremantle
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Newcastle Mater Misericordiae Hospital	Newcastle	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Mater Public Hospital	South Brisbane	Queensland
Australia	Royal North Shore Hospital	St. Leonards	New South Wales
Australia	St. Vincent's Hospital	Sydney	New South Wales
Australia	NSW Breast Cancer Institute	Westmead	New South Wales
Canada	Queen Elizabeth II Health Science Center	Halifax	Nova Scotia
Canada	London Health Sciences Centre	London	Ontario
Canada	Hopital Du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	Seaforth Medical Centre	Montreal	Quebec
Canada	Ottawa Regional Cancer Center - General Division	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec, Pavillion de Quebec	Quebec City	Quebec
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	Vancouver General Hospital	Vancouver	British Columbia
Denmark	Aalborg Hospital	Aalborg
Denmark	Odense University Hospital	Odense
Estonia	Tallinn Central Hospital	Tallinn
Estonia	University of Tartu	Tartu
Finland	Helsinki University Central Hospital	Helsinki
Finland	Kuopio University Hospital	Kuopio
Finland	Tampere University Hospital	Tampere
Finland	Turku University Central Hospital	Turku
France	Centre Hospitalier Regional et Universitaire d'Angers	Angers
France	CHR de Besancon - Hopital Jean Minjoz	Besancon
France	Hopital Beaujon	Clichy
France	Hopital Andre Mignot	Le Chesnay
France	Centre Hospitalier Regional de Lille	Lille
France	Hopital Edouard Herriot	Lyon
France	CHR Hotel Dieu	Nantes
France	Centre Henri Becquerel	Rouen
Germany	Zentralklinikum Augsburg	Augsburg
Germany	Universitaetsklinikum Charite	Berlin
Germany	Evang. Diakonissenanstalt	Bremen
Germany	Medizinische Klinik I	Dresden
Germany	Universitaetsklinik und Strahlenklinik - Essen	Essen
Germany	Klinikum der J.W. Goethe Universitaet	Frankfurt
Germany	Martin Luther Universitaet	Halle Saale
Germany	Universitats-Krankenhaus Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Medizinische Klinik und Poliklinik	Heidelberg
Germany	Staedtische Kliniken Osnabruek	Osnabruck
Germany	Universitat Rostock	Rostock
Germany	Caritasklinik St. Theresa	Saarbrucken
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Germany	Klinikum der Universitaet Ulm	Ulm
Germany	Medizinische Poliklinik der Universitat	Wurzburg
Israel	Rambam Medical Center	Haifa
Israel	Hadassah University Hospital	Jerusalem
Israel	Rabin Medical Center	Petach-Tikva
Israel	Sheba Medical Center	Ramat Gan
Israel	Kaplan Hospital	Rehovot
Israel	Tel-Aviv Medical Center-Ichilov Hospital	Tel-Aviv
New Zealand	University of Auckland School of Medicine	Auckland
New Zealand	Canterbury Health Laboratories	Christchurch
New Zealand	Waikato Hospital	Hamilton
New Zealand	Palmerston North Hospital	Palmerston North
New Zealand	Wellington Hospital	Wellington
Sweden	County Hospital (Malar Hospital)	Eskilstuna
Sweden	Sahlgrenska University Hospital	Gothenburg (Goteborg)
Sweden	County Hospital/Kalmar	Kalmar
Sweden	Central Hospital	Karlstad
Sweden	University Hospital of Linkoping	Linkoping
Sweden	Lund University Hospital	Lund
Sweden	Malmo University Hospital	Malmo
Sweden	Regional Hospital	Orebro
Sweden	County Hospital (Karnsjukhuset)	Skovde
Sweden	Huddinge Hospital	Stockholm
Sweden	Karolinska Hospital	Stockholm
Sweden	County Hospital/Sundsvall	Sundsvall
Sweden	County Hospital/Uddevalla	Uddevalla
Sweden	Umea Universitet	Umea
Sweden	University Hospital - Uppsala	Uppsala
Sweden	County Hospital/Vasteras	Vasteras
United Kingdom	Birmingham Heartlands and Solihull NHS Trust (Teaching)	Birmingham	England
United Kingdom	Leeds Teaching Hospital Trust	Leeds	England
United Kingdom	Manchester Royal Infirmary	Manchester	England
United States	University of New Mexico Cancer Research & Treatment Center	Albuquerque	New Mexico
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama
United States	Bethesda Bone Marrow Stem Cell Transplant Institute	Boynton Beach	Florida
United States	Our Lady of Mercy Medical Center	Bronx	New York
United States	Ireland Cancer Center	Cleveland	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	University of Florida Health Science Center - Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Scripps Clinic	La Jolla	California
United States	Nevada Cancer Center	Las Vegas	Nevada
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Boston Cancer Group	Memphis	Tennessee
United States	West Clinic, P.C.	Memphis	Tennessee
United States	New York Presbyterian Hospital - Cornell Campus	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Nevada Medical Group-Internal Medicine	Reno	Nevada
United States	University of Rochester Cancer Center	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Cancer Care Institute of South Texas	San Antonio	Texas
United States	South Texas Cancer Institute	San Antonio	Texas
United States	Kaiser Permanente-Southern California Permanente Medical Group	San Diego	California
United States	Sidney Kimmel Cancer Center	San Diego	California
United States	Pacific Hematology/Oncology	San Francisco	California
United States	Maine Center for Cancer Medicine and Blood Disorders	Scarborough	Maine
United States	Providence Hospital Cancer Center	Southfield	Michigan
United States	Arizona Cancer Center	Tucson	Arizona
United States	New York Medical College	Valhalla	New York
United States	Oncology and Hematology Associates	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Maxim Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Denmark,  Estonia,  Finland,  France,  Germany,  Israel,  New Zealand,  Sweden,  United Kingdom, 

References & Publications (2)

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 — View 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: 10.1186/1745-6 — View Citation