Comparison of Pixantrone + Rituximab With Gemcitabine + Rituximab in Patients With Aggressive B-cell Non-Hodgkin Lymphoma or Follicular Grade 3 Lymphoma Who Have Relapsed After Therapy and Are Not Eligible for Stem Cell Transplant (PIX-R)

• ClinicalTrials.gov Identifier: NCT01321541
• Recruitment Status: Completed
• First Posted: March 23, 2011
• Last Update Posted: October 17, 2018
• Sponsor: CTI BioPharma
• Information provided by (Responsible Party): CTI BioPharma

Tracking Information

• First Submitted Date: March 21, 2011
• First Posted Date: March 23, 2011
• Last Update Posted Date: October 17, 2018
• Actual Study Start Date: April 20, 2011
• Actual Primary Completion Date: June 28, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 16, 2014)

Progression Free Survival (PFS) [ Time Frame: Randomization to the date of disease progression or death ]

PFS is defined as the time of randomization to the date of disease progression or death due to any cause (whichever occurs first)

Original Primary Outcome Measures (submitted: March 22, 2011)

PFS and OS Analyses [ Time Frame: Disease assessments are scheduled at baseline, every 8 weeks ± 1 week during study treatment and the Early Follow-up period (24 weeks), and every 12 weeks ± 2 weeks during Intermediate Follow-up (72 weeks). ]

Progression Free Survival (PFS) between the two study arms will be determined. PFS is defined as the time between randomization and relapse (or death), whichever occurs first. Overall Survival (OS), defined as the time from randomization to death, will be determined.

Current Secondary Outcome Measures (submitted: September 16, 2014)

• Overall survival [ Time Frame: From randomization to death. ]
  Overall survival is from randomization to death due to any cause
• Complete Response Rate [ Time Frame: From randomization to death ]
  CRR is defined as the proportion of patients who achieve a CR without additional therapy.
• Overall Response Rate [ Time Frame: From randomization to death ]
  ORR is defined as the proportion of patients who achieve a CR or PR without additional therapy.
• Safety Evaluation [ Time Frame: From randomization to death ]
  The assessment of safety will be mainly on the frequency of adverse events and on the number of laboratory values that fall outside of predetermined ranges.

Original Secondary Outcome Measures (submitted: March 22, 2011)

• Overall Response Rate [ Time Frame: Disease assessments are scheduled at baseline, every 8 weeks ± 1 week during study treatment and the Early Follow-up period (24 weeks), and every 12 weeks ± 2 weeks during Intermediate Follow-up (72 weeks). ]
• Complete Response Rate [ Time Frame: Disease assessments are scheduled at baseline, every 8 weeks ± 1 week during study treatment and the Early Follow-up period (24 weeks), and every 12 weeks ± 2 weeks during Intermediate Follow-up (72 weeks). ]

Current Other Pre-specified Outcome Measures (submitted: August 17, 2016)

• Individual concentration-time profiles of patients will be compared to existing data using simulations (Visual Predictive Checks) [ Time Frame: within 1 hour of initiation of infusion to 24-48 hours after start of pixantrone infusion ]
  To characterize the PK profile of pixantrone when co-administered with rituximab. Plasma samples for PK analysis will be collected relative to the D-1 dose of pixantrone in one of the 6 treatment cycles for each participating patient. The goal is to enroll approx. 20 patients, active at 20 sites- Beatson West of Scotland Cancer Center, Uni. Hospital Kralovske Vinohrady, Uni. Hospital Hradec Kralove Hematooncology, Hospital Nuernberg, St. Marien Hospital Hamm, Puerta del Mar Hospital, Tokuda Hospital Sofia, National Center of Hematology & Transfusiology, UMHAT "SV. IVAN RILSKI", Moritz Kaposi General Hospital, Uni. of Debrecen, Polish Red Cross Marine Hospital, Kharkiv Regional Clinical Oncology Center, National Inst. of Cancer Ukraine, Cherkasy Regional Oncology Center, Inst. of Blood Pathology & Transfusion Medicine, Uni. Hospital Martin, National Onclogy Inst., Uni. Hospital with Outpatient Clinic F.D. Roosevelt Banska Bystrica, Uni. Hospital J.A. Reiman Presov
• To generate individual secondary PK parameters (eg, exposure, half-life etc.) using descriptive statistics [ Time Frame: within 1 hour of initiation of infusion to 24-48 hours after start of pixantrone infusion ]
  To characterize the PK profile of pixantrone when co-administered with rituximab. Plasma samples for PK analysis will be collected relative to the D-1 dose of pixantrone in one of the 6 treatment cycles for each participating patient. The goal is to enroll approx. 20 patients, active at 20 sites- Beatson West of Scotland Cancer Center, Uni. Hospital Kralovske Vinohrady, Uni. Hospital Hradec Kralove Hematooncology, Hospital Nuernberg, St. Marien Hospital Hamm, Puerta del Mar Hospital, Tokuda Hospital Sofia, National Center of Hematology & Transfusiology, UMHAT "SV. IVAN RILSKI", Moritz Kaposi General Hospital, Uni. of Debrecen, Polish Red Cross Marine Hospital, Kharkiv Regional Clinical Oncology Center, National Inst. of Cancer Ukraine, Cherkasy Regional Oncology Center, Inst. of Blood Pathology & Transfusion Medicine, Uni. Hospital Martin, National Onclogy Inst., Uni. Hospital with Outpatient Clinic F.D. Roosevelt Banska Bystrica, Uni. Hospital J.A. Reiman Presov

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparison of Pixantrone + Rituximab With Gemcitabine + Rituximab in Patients With Aggressive B-cell Non-Hodgkin Lymphoma or Follicular Grade 3 Lymphoma Who Have Relapsed After Therapy and Are Not Eligible for Stem Cell Transplant
• Official Title: A Randomized Multicenter Study Comparing Pixantrone + Rituximab With Gemcitabine + Rituximab in Patients With Aggressive B-cell Non-Hodgkin Lymphoma Who Have Relapsed After Therapy With CHOP-R or an Equivalent Regimen and Are Ineligible for Stem Cell Transplant
• Brief Summary: The purpose of this study is to evaluate the efficacy of Pixantrone + Rituximab compared to Gemcitabine + Rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), or follicular grade 3 lymphoma.

Detailed Description

Eligible patients will be randomized to treatment with pixantrone plus rituximab or gemcitabine plus rituximab in up to six 28-day cycles. At the time patients experience progressive disease during study treatment, early follow- up, or intermediate follow-up, they enter the survival follow up period. Patients who complete study treatment or discontinue study treatment for any other reason will participate in the follow-up periods.

Early Follow-Up: After treatment completion or discontinuation, patient will enter a 24-week follow-up period.

Intermediate Follow-Up: After completing the 24-week early follow-up period, patient will enter an additional 72-week follow-up period.

Survival Follow-Up: All patients will be monitored for survival.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment

Condition

• Diffuse Large B-cell Lymphoma
• de Novo DLBCL
• DLBCL Transformed From Indolent Lymphoma
• Follicular Grade 3 Lymphoma

Intervention

• Drug: Pixantrone + Rituximab
  Pixantrone + Rituximab: Rituximab 375 mg/m2 IV on day 1 and pixantrone 50 mg/m2 (equivalent to 85mg/m2 pixantrone dimaleate)IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.
• Drug: Gemcitabine + Rituximab
  Gemcitabine + Rituximab: Rituximab 375 mg/m2 IV on day 1 and gemcitabine 1000 mg/m2 IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.

Study Arms

• Experimental: Pixantrone + Rituximab
  Intervention: Drug: Pixantrone + Rituximab
• Active Comparator: Gemcitabine + Rituximab
  Intervention: Drug: Gemcitabine + Rituximab

• Publications *: Belada D, Georgiev P, Dakhil S, Inhorn LF, Andorsky D, Beck JT, Quick D, Pettengell R, Daly R, Dean JP, Pavlyuk M, Failloux N, Hübel K. Pixantrone-rituximab versus gemcitabine-rituximab in relapsed/refractory aggressive non-Hodgkin lymphoma. Future Oncol. 2016 Aug;12(15):1759-68. doi: 10.2217/fon-2016-0137. Epub 2016 Apr 20.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 16, 2018): 312
• Original Estimated Enrollment (submitted: March 22, 2011): 350
• Actual Study Completion Date: September 14, 2018
• Actual Primary Completion Date: June 28, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Diagnosis of DLBCL (de novo DLBCL, or transformed from indolent lymphoma) or follicular grade 3 lymphoma on the basis of tissue biopsy.
2. Patients with de novo DLBCL must have received 1-3 treatment regimens for DLBCL. Patients with follicular grade 3 lymphoma must have received 1-3 treatment regimens for follicular lymphoma (any grade). Patients with DLBCL transformed from indolent lymphoma must have received at least 1-4 treatment regimens for NHL.
3. Received rituximab containing a multi-agent therapy for the treatment of NHL.
4. Not eligible for high-dose chemotherapy and stem cell transplant.
5. Patients with DLBCL transformed from indolent lymphoma must have had a complete or partial response to a therapy for NHL lasting at least 12 weeks.

Exclusion Criteria:

1. Primary refractory de novo DLBCL or primary refractory follicular grade 3 lymphoma, defined as documented progression within 12 weeks of the last cycle of the first-line multi-agent regimen.
2. Prior treatment with cumulative dose of doxorubicin or equivalent exceeding 450 mg/m2
3. Any experimental therapy ≤ 28 days prior to randomization
4. Other malignancy within last 5 years except for the following: curatively treated basal cell/squamous cell skin cancer, carcinoma in situ of the cervix, superficial transitional cell bladder carcinoma, or in situ ductal carcinoma of the breast after complete resection
5. Any contraindication or known allergy or hypersensitivity to any study drugs
6. Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies. Low-dose corticosteroids for the treatment of non cancer-related illnesses are permitted.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Bulgaria, Czechia, Denmark, France, Germany, Hungary, Italy, Poland, Romania, Russian Federation, Slovakia, Spain, Ukraine, United Kingdom, United States
• Removed Location Countries: Canada, Czech Republic

Administrative Information

• NCT Number: NCT01321541
• Other Study ID Numbers: PIX306 (PIX-R Trial)
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: CTI BioPharma
• Study Sponsor: CTI BioPharma
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: CTI BioPharma
• Verification Date: October 2018