A Trial in Patients With Diffuse Large-B-cell Lymphoma Comparing Pixantrone Against Doxorubicin

NCT ID: NCT00268853

Last Updated: 2024-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2012-05-31

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.

Conditions

Diffuse Large-Cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

CPOP-R

Intervention Type: DRUG

Cyclophosphamide 750 mg/m2, pixantrone 150 mg/m2, vincristine 1.4 mg/m2, rituximab 375 mg.m2 on Day 1 of a 21 day cycle, for 8 cycles Prednisone 100 mg/day on Day 1-5 of a 21 day cycle for 8 cycles

2

Group Type: ACTIVE_COMPARATOR

CHOP-R

Intervention Type: DRUG

Cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, rituximab 375 mg.m2 on Day 1 of a 21 day cycle, for 8 cycles Prednisone 100 mg/day on Day 1-5 of a 21 day cycle for 8 cycles

Interventions

CPOP-R

Cyclophosphamide 750 mg/m2, pixantrone 150 mg/m2, vincristine 1.4 mg/m2, rituximab 375 mg.m2 on Day 1 of a 21 day cycle, for 8 cycles Prednisone 100 mg/day on Day 1-5 of a 21 day cycle for 8 cycles

Intervention Type: DRUG

CHOP-R

Cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, rituximab 375 mg.m2 on Day 1 of a 21 day cycle, for 8 cycles Prednisone 100 mg/day on Day 1-5 of a 21 day cycle for 8 cycles

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CTI BioPharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gabor Jurida, M.D.

Role: STUDY_DIRECTOR

CTI BioPharma

Locations

Bay Medical Oncology & Hematology

Concord, California, United States

Hazel Hawkins Hospital, Dept. of Medical Oncology

Hollister, California, United States

UCSD Moore's Cancer Center-Blood & Marrow Transplantation Division

La Jolla, California, United States

Loma Linda University Medical Center

Loma Linda, California, United States

Hematology/Oncology Group of Orange County

Orange, California, United States

Sharp Memorial Hospital

San Diego, California, United States

Rocky Mountain Cancer Center

Denver, Colorado, United States

The Center of Hematology and Oncology

Boca Raton, Florida, United States

Broward Oncology Associates

Fort Lauderdale, Florida, United States

Osceola Cancer Center

Kissimmee, Florida, United States

Watson Clinic for Cancer Care and Research

Lakeland, Florida, United States

Watson Clinic

Lakeland, Florida, United States

Memorial Cancer Institute

Pembroke Pines, Florida, United States

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, United States

Oncology Hematology Associates of West Broward

Tamarac, Florida, United States

Hematology Oncology Specialists

Tampa, Florida, United States

John B. Amos Cancer Center

Columbus, Georgia, United States

Columbus Clinic

Columbus, Georgia, United States

Oncology Hematology of Northern Illinois

Gurnee, Illinois, United States

Mid-Illinois Hematology & Oncology Associates

Normal, Illinois, United States

Cancer Care Center

New Albany, Indiana, United States

Consultants in Blood Disorders and Cancer

Louisville, Kentucky, United States

Western Kentucky Hematology/Oncology Group

Paducah, Kentucky, United States

Our Lady of the Lake Regional Medial Center, Hematology Oncology

Baton Rouge, Louisiana, United States

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Maryland Hematology/Oncology Associates, PA

Baltimore, Maryland, United States

Center for Cancer and Blood Disorders, P.C.

Bethesda, Maryland, United States

Frederick Memorial Hospital Cancer Center

Frederick, Maryland, United States

Tufts-New England Medical Center-The Neely Ctr for Clinical Cancer Research

Boston, Massachusetts, United States

Hubert H Humphrey Cancer Center

Robbinsdale, Minnesota, United States

North Missssppi Hematology Oncology Associates

Tupelo, Mississippi, United States

Capital Comprehensive Cancer Care

Jefferson City, Missouri, United States

Southeast Nebraska Hematology and Oncology Consultants, P.C.

Lincoln, Nebraska, United States

Nevada Cancer Institute

Las Vegas, Nevada, United States

New Mexico Hematology/Oncology Consultants

Albuquerque, New Mexico, United States

St. Luke's Roosevelt Hospital

New York, New York, United States

Interlake Foundation, Inc.

Rochester, New York, United States

Jacobi Medical Center Phase I Oncology

The Bronx, New York, United States

Our Lady of Mercy Medical Center

The Bronx, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Brody School of Medicine at East Carolina University - Leo W. Jenkins Cancer Center

Greenville, North Carolina, United States

Cancer Treatment & Research Mid-Dakota Clinic

Bismarck, North Dakota, United States

Summa Health Systems Hospitals

Akron, Ohio, United States

Barberton Citizen's Hospital

Barberton, Ohio, United States

Oncology Partners Network

Cincinnati, Ohio, United States

Dayton Clinical Oncology Program

Dayton, Ohio, United States

Northwest Kaiser Permanente

Portland, Oregon, United States

Berks Hematology-Oncology Associates Ltd.

Reading, Pennsylvania, United States

Charleston Cancer Center

Charleston, South Carolina, United States

Low County Hematology & Oncology

Mt. Pleasant, South Carolina, United States

The Family Cancer Center

Collierville, Tennessee, United States

Thompson Cancer Survival Center

Knoxville, Tennessee, United States

Sarah Cannon Cancer Center

Nashville, Tennessee, United States

Southwest Regional Cancer Center

Austin, Texas, United States

Texas Hematology Oncology Center

Dallas, Texas, United States

The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Northern Utah Hematology Oncology, P.C.

Ogden, Utah, United States

Multicare Oncology Hematology Specialists

Tacoma, Washington, United States

London Health Science Center Regional Care Program

London, Ontario, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

Queen Elizabeth II HSC

Halifax, , Canada

CHU Hotel Dieu

Nantes, , France

Hopitaux Universitaires de Strabourg - Hopital Hautepierre

Strasbourg, , France

Klinikum der Universitaet zu Koeln

Cologne, , Germany

Universitaetsklinikum Carl Gustav Carus

Dresden, , Germany

Universitaetsklinikum Duesseldorf

Düsseldorf, , Germany

Klinikum Nurnberg Nord - Medizinische

Nuremberg, , Germany

Universitaetsklinikum Wuerzburg

Würzburg, , Germany

Instituto di Ematologia "Lorenzo e Ariosto"

Bologna, , Italy

Azienda Ospedaliera Careggi

Florence, , Italy

Farmacia Osepdaliera, Odpedale Umberto I

Mestre, , Italy

Ospedal V. Cervello

Palermo, , Italy

Uiversita La Sapienza

Roma, , Italy

Policlinico S. Maria alle Scotte

Siena, , Italy

Ospedale Civile

Udine, , Italy

Countries

United States; Canada; France; Germany; Italy

References

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.

Reference Type: RESULT

PMID: 23946328 (View on PubMed)

Other Identifiers

PIX203

Identifier Type: -

Identifier Source: org_study_id