ULYM11011: Imexon for Relapsed Follicular and Aggressive Lymphomas

• Sponsor: University of Rochester (Other)
• Overall Status: Completed
• CT.gov ID: NCT01314014
• Collaborator: University of Arizona (Other)
• Enrollment: 22
• Locations: 2
• Arm: 1
• Duration (Months): 39
• Patients Per Site: 11
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether Amplimexon (imexon for injection) is effective in the treatment of indolent and aggressive lymphomas that have progressed after treatment with standard therapies.

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma; Small Lymphocytic Lymphoma; Marginal Zone Lymphoma; Lymphoplasmacytic Lymphoma; Diffuse Large B Cell Lymphoma; Mantle Cell Lymphoma; Burkitt's Lymphoma	Drug: Imexon	Phase 2

Detailed Description

A phase II exploratory trial of imexon in lymphoma is justified by: (1) the observation of clinical activity (partial response to the drug observed in phase I testing in a subject with refractory indolent lymphoma); (2) the finding that imexon prevents the development of human immunoblastic lymphoma in SCID mice; (3) the finding that lymphoma cell lines are killed by readily achievable doses; and (4) translational studies implicating the importance of the redox state of the cancer cell.

The dose and schedule chosen (1000 mg/m2 daily X 5 days every 3 weeks) is based on tolerability and subject acceptance in prior AmpliMed phase I studies.

The planned correlative studies should help to identify potential biomarkers for response to imexon and provide further insight into potential mechanisms of imexon action hypothesized from results of prior laboratory studies.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Amplimexon® (Imexon for Injection) for the Treatment of Previously Treated Follicular and Aggressive Lymphoma in Adults
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Imexon Subjects will be treated on Days 1-5 of 21-day treatment cycles for up to one year. Following pre-treatment with anti-emetics Amplimexon will be given by intravenous infusion over 60 minutes.

Drug: Imexon; Amplimexon will be administered daily on Days 1-5 of 21-day treatment cycles as an intravenous infusion over a time course of 60 minutes. Subjects will receive 17 cycles of therapy for a total of one year on treatment. The Amplimexon starting dose for each subject in this study is 1000 mg/m² on each treatment day. Dose may be reduced by 25% for toxicity; after 2 dose reductions, subjects must be withdrawn from treatment.; Other Names: Amplimexon (imexon for injection)

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate of of Participants to Imexon in the Treatment of Relapsed/Refractory Indolent and Aggressive Lymphomas [One year]

   CT, PET, or MRI scans for the assessment of objective tumor responses were performed at baseline, after cycle 2, and every 3 cycles thereafter until disease progression. Standard response criteria from the International Harmonization Project on Lymphoma were used for classification of objective tumor responses. Response was defined as PR (Regression of measuable disease and no new sites) if >= 50% decrease in sum of the product of the diameters of up to 6 largest dominant masses; no increase in size of other nodes (a) [18F]fluorodeoxyglucose (FDG)-avid or PET prior to therapy; one or more (PET) positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT.

Secondary Outcome Measures

1. Median Time to Progression Free Survival in Participants With Relapsed/Refractory Indolent and Aggressive Lymphomas [up to 25 months]

   Measured from start of treatment until disease progression or death from any cause.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Diagnosis:

Group 1: Histologically confirmed indolent NHL, including follicular (any grade), small lymphocytic lymphoma, marginal zone lymphoma and lymphoplasmacytic lymphomaGroup 2: histologically confirmed diffuse large B-cell, mantle cell, Burkitt, Burkitt-like, and diffuse large B-cell transformed from indolent non-Hodgkin's lymphoma.

1. Prior treatment:

Group 1: (indolent histologies): Patients must have demonstrated relapsed or refractory disease to 1 prior treatment regimen. The maximum number of prior regimens used for treatment is not specified.

Group 2: (aggressive histologies): Patients must have demonstrated relapsed or refractory disease to at least 1 prior treatment regimen. In the case of de novo diffuse large B-cell lymphoma, prior treatment must include R-CHOP or R-CHOP-like therapy, as well as second line autologous stem cell transplantation unless the patient is not eligible. The maximum number of prior regimens is not specified.

1. At least one target lesion, measurable by radiographic methods according to the 2007 Revised Response Criteria for Malignant Lymphoma.

2. ECOG Performance Status 0-2.

3. No clinical or laboratory evidence of central nervous system disease.

4. Adult (age 18 years or older).

5. Projected life expectancy >4 months.

6. If female, neither pregnant (negative pregnancy test required at screening) nor lactating.

7. If of child-bearing potential, must be able to use and agree to use medically acceptable contraception for the duration of the study. For female subjects who are neither post-menopausal nor surgically sterilized, this includes oral or injectable hormonal methods, barrier methods such as an intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence. Male subjects must also agree to use an acceptable method for contraception for the duration of the study.

8. No major infection or serious uncontrolled concomitant disease. Fully recovered from any major surgery.

9. No evidence of other concurrent active malignancy.

10. At least 4 weeks since any prior cancer chemotherapy (2 weeks for corticosteroids), antibody therapy, or radiotherapy.

11. Prior radiotherapy to less than an estimated 25% of the bone marrow. In addition, the target lesion(s) must not have been previously irradiated.

12. Clinical laboratory values within the following limits:

13. Hgb >/=10.0 g/dL

14. Absolute neutrophil count ANC >/=1,500/mm3

15. Platelets >/=75,000/mm3

16. Serum creatinine </=2.0 times upper limit of normal

17. Serum bilirubin </=2.0 times upper limit of normal

18. Serum AST and ALT </=3 times upper limit of normal

19. G6PD level >/= lower limit of normal

20. Able and willing to render informed consent and to follow protocol requirements.

Exclusion Criteria:

1. Diagnosis of lymphoma based on fine needle aspirate.

2. Curative therapy is indicated or possible.

3. Absence of a measurable target lesion, or the only target lesion was previously irradiated.

4. Symptoms, exam findings, or laboratory findings to suggest central nervous system disease involvement.

5. Age < 18 years

6. Projected life expectancy <4 months.

7. Pregnant or lactating.

8. Unable or unwilling to use medically acceptable contraception, if of childbearing potential.

9. Evidence of major infection or other serious uncontrolled concomitant illness. Not fully recovered from prior major surgery.

10. Evidence of other active malignancy.

11. Prior radiotherapy, antibody therapy, or cancer chemotherapy within 4 weeks before start of treatment (2 weeks for corticosteroids). Prior radiotherapy to >25% of the bone marrow.

12. Clinical laboratory values outside of permitted ranges.

13. Respiratory insufficiency requiring oxygen therapy; angina at rest, or myocardial infarction in previous 3 months; history of life threatening ventricular arrhythmia; uncompensated CHF or NYHA Grade 3 or 4 cardiac disease.

14. Unable or unwilling to give informed consent and to follow protocol requirements.

15. Failure to meet any of the eligibility criteria.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Cancer Center, University of Arizona	Tucson	Arizona	United States	85724
2	University of Rochester Medical Center	Rochester	New York	United States	14642

Sponsors and Collaborators

• University of Rochester
• University of Arizona

Investigators

• Principal Investigator: Paul M Barr, MD, University of Rochester

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Paul Barr, Assistant Professor, University of Rochester
• ClinicalTrials.gov Identifier: NCT01314014
• Other Study ID Numbers: 36191
• First Posted: Mar 14, 2011
• Last Update Posted: Jan 6, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Paul Barr, Assistant Professor, University of Rochester: Non Hodgkin's Lymphoma; Lymphoma, Low Grade; Lymphoma, Intermediate Grade; Lymphoma, High Grade; Lymphoma, B Cell
• Additional relevant MeSH terms: Burkitt Lymphoma; Lymphoma; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Waldenstrom Macroglobulinemia

Study Results

Participant Flow

Recruitment Details	Recruitment for this study occured at two academic medical centers (University of Rochester and Arizona Cancer Center) from June 7, 2011 through March 4, 2013.

Arm/Group Title	Imexon
Arm/Group Description	Subjects will be treated on Days 1-5 of 21-day treatment cycles for up to one year. Following pre-treatment with anti-emetics Amplimexon will be given by intravenous infusion over 60 minutes. Imexon: Amplimexon will be administered daily on Days 1-5 of 21-day treatment cycles as an intravenous infusion over a time course of 60 minutes. Subjects will receive 17 cycles of therapy for a total of one year on treatment. The Amplimexon starting dose for each subject in this study is 1000 mg/m² on each treatment day. Dose may be reduced by 25% for toxicity; after 2 dose reductions, subjects must be withdrawn from treatment.
Period Title: Overall Study
STARTED	22
COMPLETED	22
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Imexon
Arm/Group Description	Subjects will be treated on Days 1-5 of 21-day treatment cycles for up to one year. Following pre-treatment with anti-emetics Amplimexon will be given by intravenous infusion over 60 minutes. Imexon: Amplimexon will be administered daily on Days 1-5 of 21-day treatment cycles as an intravenous infusion over a time course of 60 minutes. Subjects will receive 17 cycles of therapy for a total of one year on treatment. The Amplimexon starting dose for each subject in this study is 1000 mg/m² on each treatment day. Dose may be reduced by 25% for toxicity; after 2 dose reductions, subjects must be withdrawn from treatment.
Overall Participants	22
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64
Sex: Female, Male (Count of Participants)
Female	9 40.9%
Male	13 59.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	22 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 9.1%
Not Hispanic or Latino	20 90.9%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	22 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate of of Participants to Imexon in the Treatment of Relapsed/Refractory Indolent and Aggressive Lymphomas
Description	CT, PET, or MRI scans for the assessment of objective tumor responses were performed at baseline, after cycle 2, and every 3 cycles thereafter until disease progression. Standard response criteria from the International Harmonization Project on Lymphoma were used for classification of objective tumor responses. Response was defined as PR (Regression of measuable disease and no new sites) if >= 50% decrease in sum of the product of the diameters of up to 6 largest dominant masses; no increase in size of other nodes (a) [18F]fluorodeoxyglucose (FDG)-avid or PET prior to therapy; one or more (PET) positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

20 subjects were evaluable for response, 2 subjects discontinued therapy during cycle 1 due to progressive disease and grade 5 sepsis respectively.

Arm/Group Title	Imexon
Arm/Group Description	Subjects will be treated on Days 1-5 of 21-day treatment cycles for up to one year. Following pre-treatment with anti-emetics Amplimexon will be given by intravenous infusion over 60 minutes. Imexon: Amplimexon will be administered daily on Days 1-5 of 21-day treatment cycles as an intravenous infusion over a time course of 60 minutes. Subjects will receive 17 cycles of therapy for a total of one year on treatment. The Amplimexon starting dose for each subject in this study is 1000 mg/m² on each treatment day. Dose may be reduced by 25% for toxicity; after 2 dose reductions, subjects must be withdrawn from treatment.
Measure Participants	20
Number (95% Confidence Interval) [percentage of participants]	30 136.4%

2. Secondary Outcome

Title	Median Time to Progression Free Survival in Participants With Relapsed/Refractory Indolent and Aggressive Lymphomas
Description	Measured from start of treatment until disease progression or death from any cause.
Time Frame	up to 25 months

Outcome Measure Data

Analysis Population Description

20 subjects were evaluable for response, 2 subjects discontinued therapy during cycle 1 due to progressive disease and grade 5 sepsis respectively.

Arm/Group Title	Imexon
Arm/Group Description	Subjects will be treated on Days 1-5 of 21-day treatment cycles for up to one year. Following pre-treatment with anti-emetics Amplimexon will be given by intravenous infusion over 60 minutes. Imexon: Amplimexon will be administered daily on Days 1-5 of 21-day treatment cycles as an intravenous infusion over a time course of 60 minutes. Subjects will receive 17 cycles of therapy for a total of one year on treatment. The Amplimexon starting dose for each subject in this study is 1000 mg/m² on each treatment day. Dose may be reduced by 25% for toxicity; after 2 dose reductions, subjects must be withdrawn from treatment.
Measure Participants	20
Median (Full Range) [months]	2.4

Adverse Events

Time Frame	From first dose of study treatment through 30 days after last dose.
Adverse Event Reporting Description	For each subject, AE recording began on Day 1 of the first treatment cycle, and continued until the subject completed the protocol or withdrew from the study for any reason. AEs were followed clinically until they resolved or 30 days after the last dose of study drug was received, whichever occured first.
Arm/Group Title	Imexon
Arm/Group Description	Subjects will be treated on Days 1-5 of 21-day treatment cycles for up to one year. Following pre-treatment with anti-emetics Amplimexon will be given by intravenous infusion over 60 minutes. Imexon: Amplimexon will be administered daily on Days 1-5 of 21-day treatment cycles as an intravenous infusion over a time course of 60 minutes. Subjects will receive 17 cycles of therapy for a total of one year on treatment. The Amplimexon starting dose for each subject in this study is 1000 mg/m² on each treatment day. Dose may be reduced by 25% for toxicity; after 2 dose reductions, subjects must be withdrawn from treatment.
All Cause Mortality
	Imexon
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Imexon
	Affected / at Risk (%)	# Events
Total	9/22 (40.9%)
Gastrointestinal disorders
Vomiting	2/22 (9.1%)	2
Infections and infestations
Lung infection	1/22 (4.5%)	1
Sepsis	2/22 (9.1%)	2
Urinary tract infection	1/22 (4.5%)	1
Investigations
Creatinine increased	1/22 (4.5%)	1
Metabolism and nutrition disorders
Dehydration	1/22 (4.5%)	1
Nervous system disorders
Transient ischemic attack	1/22 (4.5%)	1
Renal and urinary disorders
Hyperuricemia	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Bronchial infection	1/22 (4.5%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/22 (4.5%)	1
Vascular disorders
Hypotension	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	Imexon
	Affected / at Risk (%)	# Events
Total	22/22 (100%)
Blood and lymphatic system disorders
Anemia	11/22 (50%)	29
White blood cell decreased	8/22 (36.4%)	14
Platelet count decreased	8/22 (36.4%)	19
Gastrointestinal disorders
Diarrhea	16/22 (72.7%)	28
Nausea	15/22 (68.2%)	23
Constipation	9/22 (40.9%)	11
Vomiting	6/22 (27.3%)	7
Abdominal pain	5/22 (22.7%)	6
Oral dysesthesia	3/22 (13.6%)	3
General disorders
Fatigue	20/22 (90.9%)	26
Fever	10/22 (45.5%)	14
Chills	7/22 (31.8%)	7
Malaise	4/22 (18.2%)	4
Edema limbs	4/22 (18.2%)	4
Infections and infestations
Respiratory infection	4/22 (18.2%)	6
Investigations
Neutrophil count decreased	5/22 (22.7%)	18
Weight loss	5/22 (22.7%)	7
Creatinine increased	3/22 (13.6%)	4
Alanine aminotransferase increased	3/22 (13.6%)	4
Metabolism and nutrition disorders
Anorexia	8/22 (36.4%)	10
Hypocalcemia	6/22 (27.3%)	11
Dehydration	5/22 (22.7%)	5
Hypoalbuminemia	4/22 (18.2%)	7
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	3/22 (13.6%)	3
Back pain	3/22 (13.6%)	3
Nervous system disorders
Headache	5/22 (22.7%)	5
Dysgeusia	4/22 (18.2%)	4
Paresthesia	3/22 (13.6%)	4
Psychiatric disorders
Insomnia	3/22 (13.6%)	3
Respiratory, thoracic and mediastinal disorders
Cough	8/22 (36.4%)	8
Dyspnea	4/22 (18.2%)	4
Skin and subcutaneous tissue disorders
Rash	3/22 (13.6%)	4
Vascular disorders
Hypotension	4/22 (18.2%)	4

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.