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

• Sponsor: Spectrum Pharmaceuticals, Inc (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01549886
• Collaborator: (none)
• Enrollment: 5
• Locations: 9
• Arms: 2
• Duration (Months): 42
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma	Drug: Y-90-Zevalin; Drug: Moxtezafin Gadolinium; Drug: Rituximab	Phase 2

Detailed Description

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 enrolled in the study (approximately 50 in each group at 15 clinical sites in North America).

Patients 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 randomized 1:1 to receive either Zevalin or Zevalin and motexafin gadolinium.

Patients 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 performed at Month 12.

Disease status assessed using positron emission tomography (PET) or PET/computerized tomography (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 assessed are complete response rate and overall response rate.

Safety was assessed by adverse events, physical examinations, vital signs, and clinical laboratory assessments. Serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs) was 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MGD + Rituximab + Y-90-Zevalin 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; Day 8 - Y-90-Zevalin 0.4 mCi/kg 10-minute intravenous push; Other Names: [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/m^2 intravenous infusion. Day 8-11 Motexafin gadolinium 5 mg/kg intravenously once daily; Other Names: MGD ; Drug: Rituximab; Day 1 and Day 8: Rituximab 250 mg/m^2 intravenous infusion
Active Comparator: Rituximab + Y-90-Zevalin 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; Day 8 - Y-90-Zevalin 0.4 mCi/kg 10-minute intravenous push; Other Names: [90Y]- ibritumomab tiuxetan (Zevalin) ; Drug: Rituximab; Day 1 and Day 8: Rituximab 250 mg/m^2 intravenous infusion

Outcome Measures

Primary Outcome Measures

1. Complete Response Rate (CR) [6 Months]

Secondary Outcome Measures

1. Overall Response Rate [3 Months and 6 Months]

   Complete response rate within 3 months, overall response rate within 6 months and progression-free survival.

2. Number of Participants With Serious Adverse Events and Non-Serious Adverse Events [From time of dosing until 2 years]

   An Adverse Events (AE) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Non-SAEs was an AE events that are not Serious Adverse Events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 World Health Organization/Eastern Cooperative Oncology Group (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), Aspartate aminotransferase (AST) (Serum glutamic oxaloacetic transaminase [SGOT]) and Alanine transaminase (ALT) (Serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper limits of normal (ULN)

9. Creatinine clearance ≥ 60 mL/min/1.73 m^2

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alta Bates Summit Medical Center-Herrick	Berkeley	California	United States	94704
2	Providence Saint Joseph Medical Center	Burbank	California	United States	91505
3	Halifax Health- Center for Oncology	Daytona Beach	Florida	United States	32114
4	Rush University Medical Center	Chicago	Illinois	United States	60612
5	Loyola University Chicago	Maywood	Illinois	United States	60153
6	Oncology Specialists	Park Ridge	Illinois	United States	60068
7	University of Massachusetts - Worcester	Worcester	Massachusetts	United States	01655
8	Hackensack Medical Center	Hackensack	New Jersey	United States	07601
9	West Virginia University, WVU Healthcare	Morgantown	West Virginia	United States	26506

Sponsors and Collaborators

• Spectrum Pharmaceuticals, Inc

Investigators

• Principal Investigator: Andrew M Evens, DO, MSc, University of Massachusetts, Worcester

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Spectrum Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT01549886
• Other Study ID Numbers: SPI-MGD-11-201
• First Posted: Mar 9, 2012
• Last Update Posted: Oct 4, 2021
• Last Verified: Sep 1, 2021

• Keywords provided by Spectrum Pharmaceuticals, Inc: Non-Hodgkin's Lymphoma; Zevalin; Motexafin Gadolinium
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Rituximab

Study Results

Participant Flow

Arm/Group Title	MGD+Rituximab+Y-90-Zevalin	Rituximab+Y-90-Zevalin
Arm/Group Description	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.	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 (0.3 mCi/kg in patients with a platelet count in 100,000/μL to 149,000/μL.)
Period Title: Overall Study
STARTED	2	3
COMPLETED	0	0
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	MGD+Rituximab+Zevalin	Rituximab+Zevalin	Total
Arm/Group Description	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 mCi/kg 10-minute intravenous push (0.3 mCi/kg in patients with a platelet count in 100,000/μL to 149,000/μL.	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 (0.3 mCi/kg in patients with a platelet count in 100,000/μL to 149,000/μL.)	Total of all reporting groups
Overall Participants	2	3	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	1 33.3%	3 60%
>=65 years	0 0%	2 66.7%	2 40%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49 (2.5)	57 (6.24)	54 (4.08)
Sex: Female, Male (Count of Participants)
Female	1 50%	1 33.3%	2 40%
Male	1 50%	2 66.7%	3 60%
Region of Enrollment (Count of Participants)
United States	2 100%	3 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	Complete Response Rate (CR)
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected and analysed as no participants available for analysis and study was discontinued prematurely due to business reasons.

Arm/Group Title	MGD+Rituximab+Y-90-Zevalin	Rituximab+Y-90-Zevalin
Arm/Group Description	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.	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.) 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
Measure Participants	0	0

2. Secondary Outcome

Title	Overall Response Rate
Description	Complete response rate within 3 months, overall response rate within 6 months and progression-free survival.
Time Frame	3 Months and 6 Months

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected and analysed as no participants available for analysis and study was discontinued prematurely due to business reasons.

Arm/Group Title	MGD+Rituximab+Zevalin	Rituximab+Zevalin
Arm/Group Description	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 mCi/kg 10-minute intravenous push (0.3 mCi/kg in patients with a platelet count in 100,000/μL to 149,000/μL.	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 (0.3 mCi/kg in patients with a platelet count in 100,000/μL to 149,000/μL.)
Measure Participants	0	0

3. Secondary Outcome

Title	Number of Participants With Serious Adverse Events and Non-Serious Adverse Events
Description	An Adverse Events (AE) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Non-SAEs was an AE events that are not Serious Adverse Events.
Time Frame	From time of dosing until 2 years

Outcome Measure Data

Analysis Population Description

Safety analysis population.

Arm/Group Title	MGD+Rituximab+Y-90-Zevalin	Rituximab+Y-90-Zevalin
Arm/Group Description	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.	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.) 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
Measure Participants	2	3
Serious Adverse Events	1 50%	2 66.7%
Non-Serious Adverse Events	2 100%	3 100%

Adverse Events

Time Frame	AEs were collected from time of dosing until 2 years.
Arm/Group Title	MGD+Rituximab+Y-90-Zevalin		Rituximab+Y-90-Zevalin
Arm/Group Description	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.		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.) 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
All Cause Mortality
	MGD+Rituximab+Y-90-Zevalin		Rituximab+Y-90-Zevalin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	MGD+Rituximab+Y-90-Zevalin		Rituximab+Y-90-Zevalin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		2/3 (66.7%)
Blood and lymphatic system disorders
Anemia	0/2 (0%)	0	1/3 (33.3%)	1
Infections and infestations
UTI	0/2 (0%)	0	1/3 (33.3%)	1
Investigations
Thrombocytopenia	1/2 (50%)	1	0/3 (0%)	0
Other (Not Including Serious) Adverse Events
	MGD+Rituximab+Y-90-Zevalin		Rituximab+Y-90-Zevalin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		3/3 (100%)
Gastrointestinal disorders
Abdominal Discomfort	2/2 (100%)	2	0/3 (0%)	0
Investigations
Neutrophils count decreased	0/2 (0%)	0	3/3 (100%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.