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

Diffuse Large-Cell Lymphoma Clinical Trial

— RAPID  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00268853
• Other study ID #: PIX203
• Status: Completed
• Phase: Phase 2
• Start date: November 2005
• Est. completion date: May 2012

Study information

• Verified date: May 2024
• Source: CTI BioPharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large-Cell Lymphoma
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• 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
• 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

Locations

Country	Name	City	State
Canada	Queen Elizabeth II HSC	Halifax
Canada	London Health Science Center Regional Care Program	London	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario
France	CHU Hotel Dieu	Nantes
France	Hopitaux Universitaires de Strabourg - Hopital Hautepierre	Strasbourg
Germany	Universitaetsklinikum Carl Gustav Carus	Dresden
Germany	Universitaetsklinikum Duesseldorf	Duesseldorf
Germany	Klinikum der Universitaet zu Koeln	Koeln
Germany	Klinikum Nurnberg Nord - Medizinische	Nuernberg
Germany	Universitaetsklinikum Wuerzburg	Wuerzburg
Italy	Instituto di Ematologia "Lorenzo e Ariosto"	Bologna
Italy	Azienda Ospedaliera Careggi	Firenze
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
United States	Summa Health Systems Hospitals	Akron	Ohio
United States	New Mexico Hematology/Oncology Consultants	Albuquerque	New Mexico
United States	Southwest Regional Cancer Center	Austin	Texas
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Maryland Hematology/Oncology Associates, PA	Baltimore	Maryland
United States	Barberton Citizen's Hospital	Barberton	Ohio
United States	Our Lady of the Lake Regional Medial Center, Hematology Oncology	Baton Rouge	Louisiana
United States	Center for Cancer and Blood Disorders, P.C.	Bethesda	Maryland
United States	Cancer Treatment & Research Mid-Dakota Clinic	Bismarck	North Dakota
United States	The Center of Hematology and Oncology	Boca Raton	Florida
United States	Tufts-New England Medical Center-The Neely Ctr for Clinical Cancer Research	Boston	Massachusetts
United States	Jacobi Medical Center Phase I Oncology	Bronx	New York
United States	Our Lady of Mercy Medical Center	Bronx	New York
United States	Charleston Cancer Center	Charleston	South Carolina
United States	Oncology Partners Network	Cincinnati	Ohio
United States	The Family Cancer Center	Collierville	Tennessee
United States	Columbus Clinic	Columbus	Georgia
United States	John B. Amos Cancer Center	Columbus	Georgia
United States	Bay Medical Oncology & Hematology	Concord	California
United States	Texas Hematology Oncology Center	Dallas	Texas
United States	Dayton Clinical Oncology Program	Dayton	Ohio
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Broward Oncology Associates	Fort Lauderdale	Florida
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	Frederick Memorial Hospital Cancer Center	Frederick	Maryland
United States	Brody School of Medicine at East Carolina University - Leo W. Jenkins Cancer Center	Greenville	North Carolina
United States	Oncology Hematology of Northern Illinois	Gurnee	Illinois
United States	Hazel Hawkins Hospital, Dept. of Medical Oncology	Hollister	California
United States	Capital Comprehensive Cancer Care	Jefferson City	Missouri
United States	Osceola Cancer Center	Kissimmee	Florida
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	UCSD Moore's Cancer Center-Blood & Marrow Transplantation Division	La Jolla	California
United States	Watson Clinic	Lakeland	Florida
United States	Watson Clinic for Cancer Care and Research	Lakeland	Florida
United States	Nevada Cancer Institute	Las Vegas	Nevada
United States	Southeast Nebraska Hematology and Oncology Consultants, P.C.	Lincoln	Nebraska
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Consultants in Blood Disorders and Cancer	Louisville	Kentucky
United States	Low County Hematology & Oncology	Mount Pleasant	South Carolina
United States	Sarah Cannon Cancer Center	Nashville	Tennessee
United States	Cancer Care Center	New Albany	Indiana
United States	St. Luke's Roosevelt Hospital	New York	New York
United States	Mid-Illinois Hematology & Oncology Associates	Normal	Illinois
United States	Northern Utah Hematology Oncology, P.C.	Ogden	Utah
United States	Hematology/Oncology Group of Orange County	Orange	California
United States	Western Kentucky Hematology/Oncology Group	Paducah	Kentucky
United States	Memorial Cancer Institute	Pembroke Pines	Florida
United States	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida
United States	Northwest Kaiser Permanente	Portland	Oregon
United States	Berks Hematology-Oncology Associates Ltd.	Reading	Pennsylvania
United States	Hubert H Humphrey Cancer Center	Robbinsdale	Minnesota
United States	Interlake Foundation, Inc.	Rochester	New York
United States	Sharp Memorial Hospital	San Diego	California
United States	Multicare Oncology Hematology Specialists	Tacoma	Washington
United States	Oncology Hematology Associates of West Broward	Tamarac	Florida
United States	Hematology Oncology Specialists	Tampa	Florida
United States	North Missssppi Hematology Oncology Associates	Tupelo	Mississippi

Sponsors (1)

Lead Sponsor	Collaborator
CTI BioPharma

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy, 

References & Publications (1)

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 l — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate		Subjects followed for 5 years post treatment
Secondary	Overall Survival	Overall Survival time frame is from the interval between the date of randomization and death due to any cause and measures the total number of deaths.	The interval between the date of randomization and death due to any cause (up to 100 weeks)
Secondary	Median Progression Free Survival (PFS)	The interval between the date of randomization and the event of disease progression or relapse, institution of a new anticancer treatment or death.	From the date of randomization to the first documented disease progression or death (up to 100 weeks)
Secondary	Overall Objective Response Rate		Subjects followed for 5 years post treatment
Secondary	Time to Treatment Failure		Subjects followed for 5 years post treatment