Clinical trial NCT00268853: A Trial in Patients With Diffuse Large-B-cell Lymphoma Comparing Pixantrone Against Doxorubicin
Official title: Cyclophosphamide, Doxorubicin, Vincristine, Prednisone Plus Rituximab (CHOP-R) and Cyclophosphamide, Pixantrone, Vincristine, Prednisone Plus Rituximab (CPOP-R) in Patients With Diffuse Large-B-cell Lymphoma: A Phase II, Randomized, Multicenter, Comparative Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diffuse Large-Cell Lymphoma
Keywords: lymphoma
NHL
large cell
phase II
CHOP R
CPOP R
non Hodgkins
Lead sponsor: CTI BioPharma
Sponsor class: INDUSTRY
First posted: 2005-12-23
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the standard CHOP-R regimen of Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, and Rituximab to CPOP-R (same regimen, but substituting Doxorubicin with Pixantrone). The objective is to show that CPOP-R is not inferior to CHOP-R.

Detailed description: In preclinical studies, pixantrone has shown significantly less cardiotoxicity than other anthracyclines or anthracenediones. In addition, patients with relapsed disease, who have received prior maximum doses of anthracyclines, have tolerated high doses of pixantrone with minimal added cardiotoxicity. Pixantrone is currently being studied in a Phase III study in 3rd line aggressive NHL.

Eligibility criteria: Inclusion Criteria:

1. Previously untreated and histologically confirmed diffuse large B-cell lymphoma according to REAL/WHO classification.
2. Stage II, III or IV disease
3. CD20+
4. Age ≥ 18 years
5. ECOG performance status ≤ 2
6. At least one objectively bidimensionally measurable lesion as demonstrated by CT, spiral CT, or MRI that can be followed for response as target lesion. Patients with the following sites of disease are NOT eligible:

   * Patients with only skin lesions or only palpable lymph nodes.
   * Patients with spleen or bone marrow as only site of disease.
7. Life expectancy ≥ 3 months
8. Serum bilirubin ≤ 1.5 x the institution's upper limit normal (ULN) and creatinine ≤ 2.0 ULN and AST or ALT ≤ 2.0 x the institution's ULN. If hepatic involvement by lymphoma is present, AST or ALT may be ≤ 5.0 x the institution's ULN.
9. LVEF ≥ 50% determined by MUGA scan.
10. Ability to comply with the visit schedule and assessments required by the protocol.
11. Signed approved informed consent, with understanding of study procedures.

Exclusion Criteria:

1. Any prior chemotherapy (except intrathecal chemotherapy at diagnosis and pretreatment corticosteroid therapy) or radiotherapy: Patients may receive corticosteroid pretreatment therapy for up to 7 days after randomization, pending Investigator's decision to reduce tumor burden.
2. Histological diagnosis of T-cell lymphoma or any B-cell lymphoma other than diffuse large B-cell.
3. History of indolent lymphoma
4. Active CNS involvement based on clinical evaluation .
5. HIV-related lymphoma.
6. Major thoracic and/or abdominal surgery within the 4 weeks before randomization from which the patient has not fully recovered except for diagnosis of NHL. Patients who have had minor surgery may be enrolled after a ≥ 1 week recovery period except for diagnosis of NHL.
7. Clinically significant cardiovascular abnormalities
8. Serious (NCI CTCAE grade 3-4) intercurrent infection at randomization or deep seated or systemic mycotic infections.
9. Clinical symptoms suggesting unresolved HIV, HBV or HCV infection. Patients with seropositivity presumed to be due to prior vaccination against Hepatitis B virus or resolved infection will not be excluded.
10. Active or history of another malignancy except cured basal cell carcinoma of skin or carcinoma in situ of uterine cervix. Patients who have been in remission from another previous malignancy for \>5 years will be considered eligible.
11. Known hypersensitivity to the excipients or the study drugs that the patient will receive.
12. Any contraindications to the study drugs as described in the Summary of Product Characteristics or package inserts. 13. Neurological contraindication to vincristine (e.g. peripheral neuropathy).

14. Any condition which, in the judgment of the Investigator, would place the subject at undue risk, interfere with the results of the study, or make the subject otherwise unsuitable. 15. General status that, in the opinion of the Investigator does not permit the administration of eight courses of CHOP-R/CPOP-R. 16. Treatment with any other investigational study drug within 30 days before randomization. Patient must have recovered from all side effects of other investigational therapy. 17. Potentially fertile men and women and their sexual partners not willing to use adequate contraception as defined by the Investigator during the study and for 6 months after the last day of study drug administration.

18. Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up.

Primary outcomes:
measure: Response Rate
timeFrame: Subjects followed for 5 years post treatment
Secondary outcomes:
measure: Overall Survival
timeFrame: The interval between the date of randomization and death due to any cause (up to 100 weeks)
measure: Median Progression Free Survival (PFS)
timeFrame: From the date of randomization to the first documented disease progression or death (up to 100 weeks)
measure: Overall Objective Response Rate
timeFrame: Subjects followed for 5 years post treatment
measure: Time to Treatment Failure
timeFrame: Subjects followed for 5 years post treatment
Other outcomes:
Locations:
city: Concord
country: United States
facility: Bay Medical Oncology & Hematology
state: California
city: Hollister
country: United States
facility: Hazel Hawkins Hospital, Dept. of Medical Oncology
state: California
city: La Jolla
country: United States
facility: UCSD Moore's Cancer Center-Blood & Marrow Transplantation Division
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Orange
country: United States
facility: Hematology/Oncology Group of Orange County
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Boca Raton
country: United States
facility: The Center of Hematology and Oncology
state: Florida
city: Fort Lauderdale
country: United States
facility: Broward Oncology Associates
state: Florida
city: Kissimmee
country: United States
facility: Osceola Cancer Center
state: Florida
city: Lakeland
country: United States
facility: Watson Clinic for Cancer Care and Research
state: Florida
city: Lakeland
country: United States
facility: Watson Clinic
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Tamarac
country: United States
facility: Oncology Hematology Associates of West Broward
state: Florida
city: Tampa
country: United States
facility: Hematology Oncology Specialists
state: Florida
city: Columbus
country: United States
facility: John B. Amos Cancer Center
state: Georgia
city: Columbus
country: United States
facility: Columbus Clinic
state: Georgia
city: Gurnee
country: United States
facility: Oncology Hematology of Northern Illinois
state: Illinois
city: Normal
country: United States
facility: Mid-Illinois Hematology & Oncology Associates
state: Illinois
city: New Albany
country: United States
facility: Cancer Care Center
state: Indiana
city: Louisville
country: United States
facility: Consultants in Blood Disorders and Cancer
state: Kentucky
city: Paducah
country: United States
facility: Western Kentucky Hematology/Oncology Group
state: Kentucky
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Regional Medial Center, Hematology Oncology
state: Louisiana
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Maryland Hematology/Oncology Associates, PA
state: Maryland
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders, P.C.
state: Maryland
city: Frederick
country: United States
facility: Frederick Memorial Hospital Cancer Center
state: Maryland
city: Boston
country: United States
facility: Tufts-New England Medical Center-The Neely Ctr for Clinical Cancer Research
state: Massachusetts
city: Robbinsdale
country: United States
facility: Hubert H Humphrey Cancer Center
state: Minnesota
city: Tupelo
country: United States
facility: North Missssppi Hematology Oncology Associates
state: Mississippi
city: Jefferson City
country: United States
facility: Capital Comprehensive Cancer Care
state: Missouri
city: Lincoln
country: United States
facility: Southeast Nebraska Hematology and Oncology Consultants, P.C.
state: Nebraska
city: Las Vegas
country: United States
facility: Nevada Cancer Institute
state: Nevada
city: Albuquerque
country: United States
facility: New Mexico Hematology/Oncology Consultants
state: New Mexico
city: Bronx
country: United States
facility: Jacobi Medical Center Phase I Oncology
state: New York
city: Bronx
country: United States
facility: Our Lady of Mercy Medical Center
state: New York
city: New York
country: United States
facility: St. Luke's Roosevelt Hospital
state: New York
city: Rochester
country: United States
facility: Interlake Foundation, Inc.
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: Brody School of Medicine at East Carolina University - Leo W. Jenkins Cancer Center
state: North Carolina
city: Bismarck
country: United States
facility: Cancer Treatment & Research Mid-Dakota Clinic
state: North Dakota
city: Akron
country: United States
facility: Summa Health Systems Hospitals
state: Ohio
city: Barberton
country: United States
facility: Barberton Citizen's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Partners Network
state: Ohio
city: Dayton
country: United States
facility: Dayton Clinical Oncology Program
state: Ohio
city: Portland
country: United States
facility: Northwest Kaiser Permanente
state: Oregon
city: Reading
country: United States
facility: Berks Hematology-Oncology Associates Ltd.
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Cancer Center
state: South Carolina
city: Mount Pleasant
country: United States
facility: Low County Hematology & Oncology
state: South Carolina
city: Collierville
country: United States
facility: The Family Cancer Center
state: Tennessee
city: Knoxville
country: United States
facility: Thompson Cancer Survival Center
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Southwest Regional Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Hematology Oncology Center
state: Texas
city: Fort Worth
country: United States
facility: The Center for Cancer and Blood Disorders
state: Texas
city: Ogden
country: United States
facility: Northern Utah Hematology Oncology, P.C.
state: Utah
city: Tacoma
country: United States
facility: Multicare Oncology Hematology Specialists
state: Washington
city: London
country: Canada
facility: London Health Science Center Regional Care Program
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Halifax
country: Canada
facility: Queen Elizabeth II HSC
city: Nantes
country: France
facility: CHU Hotel Dieu
city: Strasbourg
country: France
facility: Hopitaux Universitaires de Strabourg - Hopital Hautepierre
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Koeln
country: Germany
facility: Klinikum der Universitaet zu Koeln
city: Nuernberg
country: Germany
facility: Klinikum Nurnberg Nord - Medizinische
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Bologna
country: Italy
facility: Instituto di Ematologia "Lorenzo e Ariosto"
city: Firenze
country: Italy
facility: Azienda Ospedaliera Careggi
city: Mestre
country: Italy
facility: Farmacia Osepdaliera, Odpedale Umberto I
city: Palermo
country: Italy
facility: Ospedal V. Cervello
city: Roma
country: Italy
facility: Uiversita La Sapienza
city: Siena
country: Italy
facility: Policlinico S. Maria alle Scotte
city: Udine
country: Italy
facility: Ospedale Civile
Study officials:
affiliation: CTI BioPharma
name: Gabor Jurida, M.D.
role: STUDY_DIRECTOR
References:
citation: Herbrecht R, Cernohous P, Engert A, Le Gouill S, Macdonald D, Machida C, Myint H, Saleh A, Singer J, Wilhelm M, van der Jagt R. Comparison of pixantrone-based regimen (CPOP-R) with doxorubicin-based therapy (CHOP-R) for treatment of diffuse large B-cell lymphoma. Ann Oncol. 2013 Oct;24(10):2618-2623. doi: 10.1093/annonc/mdt289. Epub 2013 Aug 14.