Imexon for Relapsed Follicular and Aggressive Lymphomas

NCT01314014 | Completed Phase 2 Results DMC

• 1 other identifier: 36191
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

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.

Conditions

Follicular Lymphoma; Small Lymphocytic Lymphoma; Marginal Zone Lymphoma; Lymphoplasmacytic Lymphoma; Diffuse Large B Cell Lymphoma; Mantle Cell Lymphoma; Burkitt's Lymphoma

Keywords

Non Hodgkin's Lymphoma; Lymphoma, Low Grade; Lymphoma, Intermediate Grade; Lymphoma, High Grade; Lymphoma, B Cell

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate of of Participants to Imexon in the Treatment of Relapsed/Refractory Indolent and Aggressive Lymphomas

  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.

  One year

Secondary Outcomes (1)

• Median Time to Progression Free Survival in Participants With Relapsed/Refractory Indolent and Aggressive Lymphomas

  up to 25 months

Study Arms (1)

Imexon

EXPERIMENTAL

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

Interventions

Imexon DRUG

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 Dose may be reduced by 25% for toxicity; after 2 dose reductions, subjects must be withdrawn from treatment.

Also known as: Amplimexon (imexon for injection)

Imexon

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• At least one target lesion, measurable by radiographic methods according to the 2007 Revised Response Criteria for Malignant Lymphoma.
• ECOG Performance Status 0-2.
• No clinical or laboratory evidence of central nervous system disease.
• Adult (age 18 years or older).
• Projected life expectancy \>4 months.
• If female, neither pregnant (negative pregnancy test required at screening) nor lactating.
• 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.
• No major infection or serious uncontrolled concomitant disease. Fully recovered from any major surgery.
• No evidence of other concurrent active malignancy.
• At least 4 weeks since any prior cancer chemotherapy (2 weeks for corticosteroids), antibody therapy, or radiotherapy.

You may not qualify if:

• Diagnosis of lymphoma based on fine needle aspirate.
• Curative therapy is indicated or possible.
• Absence of a measurable target lesion, or the only target lesion was previously irradiated.
• Symptoms, exam findings, or laboratory findings to suggest central nervous system disease involvement.
• Age \< 18 years
• Projected life expectancy \<4 months.
• Pregnant or lactating.
• Unable or unwilling to use medically acceptable contraception, if of childbearing potential.
• Evidence of major infection or other serious uncontrolled concomitant illness. Not fully recovered from prior major surgery.
• Evidence of other active malignancy.
• 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.
• Clinical laboratory values outside of permitted ranges.
• 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.
• Unable or unwilling to give informed consent and to follow protocol requirements.
• Failure to meet any of the eligibility criteria.

Sponsors & Collaborators

• University of Rochester: lead
• University of Arizona: collaborator

Study Sites (2)

Arizona Cancer Center, University of Arizona

Tucson, Arizona, 85724, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Related Publications (2)

• Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.

  PMID: 17242396 RESULT

• Barr PM, Miller TP, Friedberg JW, Peterson DR, Baran AM, Herr M, Spier CM, Cui H, Roe DJ, Persky DO, Casulo C, Littleton J, Schwartz M, Puvvada S, Landowski TH, Rimsza LM, Dorr RT, Fisher RI, Bernstein SH, Briehl MM. Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma. Blood. 2014 Aug 21;124(8):1259-65. doi: 10.1182/blood-2014-04-570044. Epub 2014 Jul 11.

  PMID: 25016003 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Burkitt Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell

Interventions

4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one; Injections

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Paul M. Barr, MD
• Organization: James P. Wilmot Cancer Center, University of Rochester

Paul_Barr@urmc.rochester.edu

585-273-3258

Study Officials

• Paul M Barr, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 10, 2011
• First Posted: March 14, 2011
• Study Start: May 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: August 1, 2014
• Last Updated: January 6, 2016
• Results First Posted: July 1, 2014

Record last verified: 2015-12

Locations

US (2)