A Phase II Study of MGCD0103 Given Three-Times Weekly In Patients With Relapsed And Refractory Lymphoma
The goal of this clinical research study is to learn the effectiveness of MGCD0103 in the treatment of patients with lymphoma that has relapsed or is refractory. The safety of this drug will also be studied.
Disease Group: Lymphoma
Treatment Agent: MGCD0103
Treatment Location: Independent Multicenter Arrangements
Estimatated Length of Stay in Houston: N/A
Return Visit: Patients will have 4 visits on Cycle 1 (on Days 1, 8, 15 and 22) and 2 visits on subsequent cycles (on Days 1 and 15) for up to 1 year. Patients should be seen 30 days after completion of therapy.
Home Care: Patients may take MGCD0103 gelcaps by mouth at home.
Primary Objective: Estimate the overall response rate (CR + CRu + PR) with MGCD0103 in patients with relapsed or refractory lymphoma. There will be 2 cohorts: Diffuse large B-cell lymphoma (DLBCL) Follicular lymphoma Secondary Objectives: Estimate duration of objective response in each population Estimate progression-free survival for each population Characterize the safety profile of MGCD0103 in each population Assess biomarkers and predictive markers for MGCD0103 Evaluate pharmacokinetic parameters of MGCD0103 in these populations (for patients at selected centers). M. D. Anderson will not participate in these PKs.
IRB Review and Approval Date: 06/21/2006
Recruitment Status: Not Accepting
Projected Accrual: 82
1) Pathologic confirmation of relapsed or refractory lymphoma: a.
Diffuse Large B-cell Lymphoma (DLBCL) stage II - IV; b. Follicular lymphoma.
2) At least one site of measurable disease (>/= 2.0 cm with conventional techniques; PE, CT, X-ray, MRI).
3) Prior treatment: a. DLBCL cohort: Disease progression following initial therapy and transplant (unless the patient is ineligible or refused transplant). There is no limit to number of prior therapies. b. Follicular lymphoma cohort: Patients with follicular lymphoma that is relapsed following or refractory to standard therapy and/or existing therapies (eg, rituximab, bendamustine hydrochloride, ibritumomab tiuxetan) or are not eligible for orare unlikely to achieve clinical benefit from those therapies. Patients must have failed 3 or more prior therapies.
4) Patients must have at least one of the following considered related to disease: a. Local symptoms due to progressive or bulky nodal disease b. Compromise of normal organ function due to progressive or bulky disease c. Presence of systemic B symptoms d. Presence of symptomatic extranodal disease e. Cytopenias due to extensive bone marrow infiltration, autoimmune hemolytic anemia or thrombocytopenia, or hypersplenism
5) ECOG performance status of 0 or 1 (must be done within 7 days prior to study initiation).
6) Age 18 years or older (no safety data yet for age < 18).
7) Laboratory requirements (must be done within 7 days prior to study initiation): Total Bilirubin </= 1.5 x Upper Limit of Normal (ULN); Aspartate Transaminase (AST /SGOT) and Alanine Transaminase (ALT /SGPT) </= 2.5 x ULN; Serum Creatinine </= 1.5 x ULN; Absolute neutrophil counts of > 1,000/microL, and platelet counts > 25,000/microL
8) Patients or their legal representative must be able to read, understand, and sign a written informed consent (approved by the institutional review board/Ethics Committee (IRB/EC)) within 28 days prior to start of treatment.
1) Patients with another active cancer (excluding basal cell carcinoma
or cervical intraepithelial neoplasia (CIN / cervical in situ) or
melanoma in situ). Prior history of cancer is allowed, as long as there
is no active disease.
2) Pregnant or lactating women. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test documented within 7 days prior to start of study drug.
3) WOCBP and men whose partners are WOCBP must use an acceptable method of contraception while enrolled on this study, and for a period of 3 months following study drug treatment. Patients unwilling or unable to follow this guideline will be excluded. An example of an acceptable form of contraception is a double barrier method, such as condom with diaphragm
4) Patients with uncontrolled intercurrent illness, active or uncontrolled infections, or a fever >38.5°C (not due to tumor fever) on the day of scheduled dosing.
5) Patients with a history of pericardial disease.
6) Patients with small, moderate or large pericardial effusions or patients with a diagnosis of pericarditis.
7) Patients with significant cardiac abnormalities such as recent (within 12 months) myocardial infarction or congestive heart failure >= Class 3, as well as symptomatic or uncontrolled atrial fibrillation, atrial flutter or sinus tachycardia.
8) Patients with serious illnesses, medical conditions, or other medical history, including laboratory results, which, in the investigator’s opinion, would be likely to interfere with a patient’s participation in the study, or with the interpretation of the results.
9) Patients who have been treated with any investigational drug within 28 days prior to study initiation (an investigational drug is one for which there is no approved indication), or who are receiving concurrent treatment with other experimental drugs or anti-cancer therapy. Patients must have recovered from all transient toxicity induced by prior therapy.
10) Known hypersensitivity to HDAC inhibitors, and to any of the components of MGCD0103 (N-(2-Amino-phenyl)-4-[4-pyridin-3-yl-pyrimidin-2-ylamino)-methyl]-benzamide dihydrobromide,microcrystalline cellulose, sodium starch glycolate, colloidal silicon dioxide, magnesium stearate (non-bovine)).
11) Known human immunodeficiency virus (HIV) or active Hepatitis B or C. Testing is not required for patients not suspected of having these conditions. For patients with a history of Hepatitis B or C that is no longer active, the Investigator should contact MethylGene in advance to confirm patient’s eligibility. The reason for this exclusion is concern for safety of patients with these infections. There are no data to date in these populations.
12) Central nervous system lymphoma and lymphoma involving the leptomeningeal area.
13) Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc) that, in the judgment of the investigator, may affect the patient’s ability to sign the informed consent and undergo study procedures.
14) Any condition that will put the patient at undue risk or discomfort as a result of adherence to study procedures. For example, consider requirement to take MGCD0103 with a low-pH drink and recommendation to avoid agents that directly increase gastric-pH.
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