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

NCT01549886 | Terminated Phase 2 Results

• 1 other identifier: SPI-MGD-11-201
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 9

Brief Summary

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 Non-Hodgkin's Lymphoma (NHL). Effectiveness of the experimental regimen 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.

Conditions

Non-Hodgkin's Lymphoma

Keywords

Non-Hodgkin's Lymphoma; Zevalin; Motexafin Gadolinium

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CR)

  6 Months

Secondary Outcomes (2)

• Overall Response Rate

  3 Months and 6 Months

• Number of Participants With Serious Adverse Events and Non-Serious Adverse Events

  From time of dosing until 2 years

Study Arms (2)

MGD + Rituximab + Y-90-Zevalin

EXPERIMENTAL

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/m\^2 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/m\^2 intravenous infusion, followed 4 hours later by Y-90-Zevalin 0.4 millicurie / kilogram (mCi/kg) 10-minute intravenous push (0.3 mCi/kg in patients with a platelet count in 100,000/μL to 149,000/μL.

Drug: Y-90-Zevalin; Drug: Moxtezafin Gadolinium; Drug: Rituximab

Rituximab + Y-90-Zevalin

ACTIVE COMPARATOR

Day 1 Rituximab 250 mg/m\^2 intravenous infusion. Day 8 Rituximab 250 mg/m\^2 intravenous infusion, followed 4 hours later by Y-90-Zevalin 0.4 mCi/kg 10-minute intravenous push

Drug: Y-90-Zevalin; Drug: Rituximab

Interventions

Y-90-Zevalin DRUG

Day 8 - Y-90-Zevalin 0.4 mCi/kg 10-minute intravenous push

Also known as: [90Y]- ibritumomab tiuxetan (Zevalin)

MGD + Rituximab + Y-90-Zevalin; Rituximab + Y-90-Zevalin

Moxtezafin Gadolinium DRUG

Day 1-4 Motexafin gadolinium 5 mg/kg intravenously once daily, followed in one hour (Day 1 only) by Day 1 Rituximab 250 mg/m\^2 intravenous infusion. Day 8-11 Motexafin gadolinium 5 mg/kg intravenously once daily

Also known as: MGD

MGD + Rituximab + Y-90-Zevalin

Rituximab DRUG

Day 1 and Day 8: Rituximab 250 mg/m\^2 intravenous infusion

MGD + Rituximab + Y-90-Zevalin; Rituximab + Y-90-Zevalin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women, at least 18 years of age
• Histologically-confirmed follicular or indolent, marginal zone and small lymphocytic B cell non-Hodgkin's lymphoma
• 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.
• 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
• A life expectancy of at least 3 months
• A World Health Organization/Eastern Cooperative Oncology Group (WHO/ECOG) performance status of 0 or 1
• 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.
• Adequate liver function: total bilirubin ≤ 2 × upper limit of normal (ULN), Aspartate aminotransferase (AST) (Serum glutamic oxaloacetic transaminase \[SGOT\]) and Alanine transaminase (ALT) (Serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 × upper limits of normal (ULN)
• Creatinine clearance ≥ 60 mL/min/1.73 m\^2
• Bone marrow involvement \< 25%
• 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
• Willing and able to provide written Informed Consent and to comply with the requirements of the study protocol

You may not qualify if:

• Received antineoplastic, experimental, and/or radiation therapy within the 3 weeks prior to Study Day 1
• Has not recovered to ≤ Grade 1 from all toxicities related to prior treatments
• Prior radioimmunotherapy for NHL
• 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
• Platelet transfusion within the 7 days prior to Study Day 1
• History of porphyria
• Grade 2 or higher peripheral neuropathy within the 14 days prior to Study Day 1
• History of or active central nervous system disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, brain metastases)
• Ongoing, active infection that requires anti infective therapy
• 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
• 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
• 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
• 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
• Evidence of a bleeding diathesis and/or a coagulopathy
• Known HIV infection

Sponsors & Collaborators

• Spectrum Pharmaceuticals, Inc: lead

Study Sites (9)

Alta Bates Summit Medical Center-Herrick

Berkeley, California, 94704, United States

Location

Providence Saint Joseph Medical Center

Burbank, California, 91505, United States

Location

Halifax Health- Center for Oncology

Daytona Beach, Florida, 32114, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Loyola University Chicago

Maywood, Illinois, 60153, United States

Location

Oncology Specialists

Park Ridge, Illinois, 60068, United States

Location

University of Massachusetts - Worcester

Worcester, Massachusetts, 01655, United States

Location

Hackensack Medical Center

Hackensack, New Jersey, 07601, United States

Location

West Virginia University, WVU Healthcare

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

ibritumomab tiuxetan; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Gajanan Bhat, PhD
• Organization: Spectrum Pharmaceuticals

Gajanan.Bhat@sppirx.com

949-743-9219

Study Officials

• Andrew M Evens, DO, MSc

  University of Massachusetts, Worcester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2012
• First Posted: March 9, 2012
• Study Start: November 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: May 1, 2015
• Last Updated: October 4, 2021
• Results First Posted: October 4, 2021

Record last verified: 2021-09

Locations

US (9)