Phase 2 Study of Zevalin Versus Zevalin and Motexafin Gadolinium in Patients With Rituximab-Refractory Low-grade or Follicular B-cell Non-Hodgkin's Lymphoma

This study has been terminated.
(Due to business reasons.)
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01549886
First received: March 6, 2012
Last updated: March 25, 2013
Last verified: March 2013

March 6, 2012
March 25, 2013
November 2011
June 2014   (final data collection date for primary outcome measure)
Complete Response Rate (CR) [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
Primary endpoint is complete response rate within 6 months
Same as current
Complete list of historical versions of study NCT01549886 on ClinicalTrials.gov Archive Site
  • Overall Response Rate [ Time Frame: 3 Months and 6 Months ] [ Designated as safety issue: No ]
    Complete response rate within 3 months, overall response rate within 6 months and progression-free survival.
  • Safety [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Treatment-emergent adverse events, deaths and other serious adverse events, adverse events resulting in withdrawal of patient, ad laboratory abnormalities.
  • Overall Response Rate [ Time Frame: 3 Months and 6 Months ] [ Designated as safety issue: No ]
    Complete response rate within 3 months, overall response rate within 6 months and progression-free survival.
  • Safety [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Treatment-emergent adverse events, deaths and other serious adverse evets, adverse events resulting in withdrawal of patient, ad laborabory abnormalities.
Not Provided
Not Provided
 
Phase 2 Study of Zevalin Versus Zevalin and Motexafin Gadolinium in Patients With Rituximab-Refractory Low-grade or Follicular B-cell Non-Hodgkin's Lymphoma
A Randomized, Open-Label, Multi-Center, Phase 2 Study of Zevalin ([90Y]- Ibritumomab Tiuxetan) Versus Zevalin and Motexafin Gadolinium in Patients With Rituximab- Refractory Low-grade or Follicular B-cell Non-Hodgkin's Lymphoma

The objectives of this study are to evaluate the efficacy and safety of the Zevalin regimen compared to Zevalin and motexafin gadolinium in patients with rituximab-refractory, low-grade or follicular NHL.

Effectiveness of the experimental regimen will be assessed by complete response rate within 6 months of study entry (primary endpoint), complete response rate within 3 months of study entry, and overall response rate within 6 month of study entry.

This multi-center, randomized, open-label study is designed to compare the safety and efficacy of therapy with Zevalin regimen versus Zevalin and motexafin gadolinium in patients with rituximab-refractory, low-grade or follicular NHL. Approximately 100 adult patients will be enrolled in the study (approximately 50 in each group at 15 clinical sites in North America).

Patients will be screened for eligibility within the 14 days prior to Day 1 of the study. Once written informed consent has been obtained and patient eligibility has been established, the patient will be randomized 1:1 to receive either Zevalin or Zevalin and motexafin gadolinium.

Patients will be assessed for safety at each visit to the study center and for disease response at Months 3, 6 and 12. An end-of-study-visit will be performed at Month 12.

Disease status will be assessed using positron emission tomography (PET) or PET/CT, and/or flow cytometry. Disease response will be evaluated in accordance with the standardized definitions and criteria of the International Working Group Revised Response Criteria for Malignant Lymphoma. The efficacy endpoints that will be assessed are complete response rate and overall response rate.

Safety will be assessed by adverse events, physical examinations, vital signs, and clinical laboratory assessments. Serious adverse events (SAEs) and treatment-emergent adverse events(TEAEs) will be collected for all patients beginning on Day 1 and continuing through the end-of study-visit to be performed at Month 12 or withdrawal from study.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Non-Hodgkin's Lymphoma
  • Drug: Zevalin Regimen
    Day 1 - Rituximab 250 mg/m2 intravenous infusion. Day 8 - Rituximab 250 mg/m2 intravenous infusion, followed 4 hours later by Y-90-Zevalin 0.4 mCi/kg 10-minute intravenous push
    Other Name: Rituximab + [90Y]- ibritumomab tiuxetan (Zevalin)
  • Drug: Moxtezafin Gadolinium

    Day 1-4 Motexafin gadolinium 5 mg/kg intravenously once daily, followed in one hour (Day 1 only) by Day 1 Rituximab 250 mg/m2 intravenous infusion.

    Day 8-11 Motexafin gadolinium 5 mg/kg intravenously once daily, followed in one hour (Day 8 only) by Day 8 Rituximab 250 mg/m2 intravenous infusion, followed 4 hours later by Y-90-Zevalin 0.4 mCi/kg 10-minute intravenous push (0.3 mCi/kg in patients with a platelet count in 100,000/μL to 149,000/μL.

    Other Name: MGD
  • Experimental: Moxtezafin Gadolinium
    Experimental Arm with Moxtezafin Gadolinium and Zevalin Regimen
    Intervention: Drug: Moxtezafin Gadolinium
  • Active Comparator: Zevalin Regimen
    Day 1 Rituximab 250 mg/m2 intravenous infusion. Day 8 Rituximab 250 mg/m2 intravenous infusion, followed 4 hours later by Y-90-Zevalin 0.4 mCi/kg 10-minute intravenous push (0.3 mCi/kg in patients with a platelet count in 100,000/μL to 149,000/μL.)
    Intervention: Drug: Zevalin Regimen
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
5
July 2016
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Men or women, at least 18 years of age
  2. Histologically-confirmed follicular or indolent, marginal zone and small lymphocytic B cell non-Hodgkin's lymphoma
  3. Progressive disease within 6 months of the end of a rituximab-containing regimen; or progressive disease at any time following 2 or more prior rituximab-containing regimens; or progressive disease while on rituximab-containing regimen.
  4. At least 1 measurable tumor (> 1.5 cm in the long axis and > 1.0 cm in the short axis) that has not been irradiated previously or that has increased in size since previous irradiation
  5. A life expectancy of at least 3 months
  6. A WHO/ECOG performance status of 0 or 1
  7. Adequate hematopoietic function: absolute neutrophil count (ANC) ≥ 1,500 cells/μL, absolute lymphocyte count (ALC) ≤ 5,000 cells/μL, platelet count ≥ 100,000 cells/μL,hemoglobin ≥ 9 g/dL (may be transfused to maintain this concentration). Patients who have received pre-phase therapy for purposes of improving performance status prior to initiating Zevalin are eligible.
  8. Adequate liver function: total bilirubin ≤ 2 × upper limit of normal (ULN), AST (SGOT)and ALT (SGPT) ≤ 2.5 × ULN
  9. Creatinine clearance ≥ 60 mL/min/1.73 m2
  10. Bone marrow involvement < 25%
  11. If men or women of reproductive potential, agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for at least 1 year following treatment with Zevalin
  12. Willing and able to provide written Informed Consent and to comply with the requirements of the study protocol

Exclusion Criteria:

  1. Received antineoplastic, experimental, and/or radiation therapy within the 3 weeks prior to Study Day 1
  2. Has not recovered to ≤ Grade 1 from all toxicities related to prior treatments
  3. Prior radioimmunotherapy for NHL
  4. Autologous stem cell transplant within the 3 months prior to Study Day 1, and/or any history of allogeneic stem cell transplant with continued allogeneic hematopoiesis
  5. Platelet transfusion within the 7 days prior to Study Day 1
  6. History of porphyria
  7. Grade 2 or higher peripheral neuropathy within the 14 days prior to Study Day 1
  8. History of or active central nervous system disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, brain metastases)
  9. Ongoing, active infection that requires anti infective therapy
  10. Clinically significant cardiovascular disease (e.g., unstable angina pectoris, serious cardiac arrhythmia requiring medication, uncontrolled hypertension, myocardial infarction, New York Heart Association [NYHA] Class 2 or higher congestive heart failure, Grade 2 or higher peripheral vascular disease) within the 12 months prior to Study Day 1
  11. History of another clinically significant medical condition, metabolic dysfunction, physical examination finding, and/or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or place the patient at high risk of treatment complications and/or of noncompliance with the study procedures
  12. Major surgical procedure and/or significant traumatic injury (that which could interfere with the patient's ability to receive protocol therapy as determined by the principal investigator) within the 28 days prior to Study Day 1, and/or patient is anticipated to require a major surgical procedure during the study period
  13. Diagnosed with and/or treated for a malignancy other than NHL within the 2 years prior to Study Day 1, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, and/or low-risk prostate cancer after curative therapy from which the patient has been disease-free for at least 1 year
  14. Evidence of a bleeding diathesis and/or a coagulopathy
  15. Known HIV infection
  16. Known hypersensitivity to drugs with porfyrin-like structures, like Visudyne™.
  17. Positive Hepatitis B or C infection: Patient must be tested for hepatitis B surface antigen.
  18. Pregnant or lactating woman
  19. Full dose oral or parenteral anticoagulants within the 10 days prior to Study Day 1, and/or anticipated full dose oral or parenteral anticoagulant therapy during the study period(except as required to maintain patency of pre-existing, permanent, indwelling intravenous catheters) or thrombolytic agents
  20. Participated in another clinical study within the 4 weeks prior to Study Day 1
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01549886
SPI-MGD-11-201
No
Spectrum Pharmaceuticals, Inc
Spectrum Pharmaceuticals, Inc
Not Provided
Principal Investigator: Andrew M Evens, DO, MSc University of Massachusetts, Worcester
Spectrum Pharmaceuticals, Inc
March 2013

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