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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)

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

Tracking Information
First Submitted Date  ICMJE March 21, 2011
First Posted Date  ICMJE March 23, 2011
Last Update Posted Date October 17, 2018
Actual Study Start Date  ICMJE April 20, 2011
Actual Primary Completion Date June 28, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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.
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE 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  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Diffuse Large B-cell Lymphoma
  • de Novo DLBCL
  • DLBCL Transformed From Indolent Lymphoma
  • Follicular Grade 3 Lymphoma
Intervention  ICMJE
  • 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  ICMJE
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 16, 2018)
312
Original Estimated Enrollment  ICMJE
 (submitted: March 22, 2011)
350
Actual Study Completion Date  ICMJE September 14, 2018
Actual Primary Completion Date June 28, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE 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  ICMJE NCT01321541
Other Study ID Numbers  ICMJE PIX306 (PIX-R Trial)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CTI BioPharma
Study Sponsor  ICMJE CTI BioPharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account CTI BioPharma
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP