Study to Evaluate how safe and how effective is CUDC-907 With and Without Rituximab in Patients With Relapsed/Refractory MYC-Altered Diffuse Large B-Cell Lymphoma
- Conditions
- Patients With Relapsed/Refractory MYC-Altered Diffuse Large B-Cell LymphomaMedDRA version: 19.0 Level: PT Classification code 10012821 Term: Diffuse large B-cell lymphoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 19.0 Level: PT Classification code 10012822 Term: Diffuse large B-cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-004509-34-ES
- Lead Sponsor
- Curis, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 120
1. Age >= 18 years.
2. At least two but no more than 4 prior lines of therapy for the treatment of DLBCL and ineligible for ASCT (or failed) autologous or allogeneic stem cell transplant (salvage therapy, conditioning therapy and maintenance with transplant will be considered one prior treatment).
3. Histopathologically confirmed diagnosis of RR DLBCL:
· Diagnosis of follicular lymphoma transformed to DLBCL (aka t-FL DLBCL) is allowed. Other B-cell lymphomas including DLBCL unclassified and Burkitt’s lymphoma are not eligible.
4. Histopathologically confirmed MYC-altered status by archival tumor samples (collected within 1 year of study entry and/or within 1 line of prior therapy, whichever is closer to the time of study entry) or fresh tumor samples by one of the following:
· Local or central laboratory (if local testing is not available) FISH results of MYC translocation, or
· Local or central laboratory (if local testing is not available) IHC results with expression of MYC >= 40%, and/or gene copy number gain by FISH
5. Confirmed availability of viable tissue (defined as archival tumor tissue collected within 1 year of study entry and/or within 1 line of prior therapy, whichever is closer to the time of study entry, or fresh tumor samples) for central laboratory FISH and IHC testing and review prior to study dosing.
6.CT scan showing at least 1 or more clearly demarcated lymph node(s) with a long axis > 1.5 cm and short axis > 1.0 cm or 1 clearly demarcated extranodal lesion(s) with a long axis > 1.0 cm and short axis > 1.0 cm. Baseline FDG-PET scans, if used, must demonstrate positive lesions compatible with CT-defined anatomical tumor sites.
7. Presence of RR disease per Revised Response Criteria for Malignant Lymphoma (Cheson et al, 2007) after receipt of at least 2 but no more than 4 prior lines of treatment for DLBCL, at least one of which included an anthracycline.
· Relapsed disease is defined by DLBCL confirmed by excisional/incisional biopsy (preferred) or fine needle aspiration (FNA) or core needle biopsy (CNB) after a complete response (CR) or unconfirmed complete response (CRu).
- For relapse during first-line treatment, biopsy/FNA reconfirmation of the lymphoma is recommended but not mandatory.
· Refractory disease is defined by (a) PD during first-line treatment, (b) stable disease (SD) after = 3 cycles of first-line treatment, or (c) partial response (PR) after = 6 cycles of first line treatment, or for stage II disease, = 3 cycles of treatment and definitive involved field radiotherapy. -
For sustained PR after first-line treatment, confirmation biopsy for DLBCL is preferred. An FNA may be acceptable, but if inappropriate (e.g., due to biopsy inaccessibility), the Sponsor may determine eligibility following review of imaging results and disease history.
-For SD or PD after first-line treatment, reconfirmation of DLBCL by biopsy (preferred) or FNA is recommended but not mandatory.
8.Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.
9.Recovery to Grade 1 or baseline of any toxicity due to prior anticancer therapies (excluding alopecia).
10.Absolute neutrophil count >= 1,000/µL; platelets >= 75,000/µL; creatinine
1. Known primary mediastinal, ocular, epidural, testicular or breast DLBCL.
2. Known lymphomatous involvement of the central nervous system (CNS) unless deemed clear of malignant involvement by cytologic examination of cerebrospinal fluid. Subjects with known bone marrow involvement will require prior chemoprophylaxis per local standard to prevent CNS relapse.
3. Known allergy or hypersensitivity to phosphatidylinositol 3 kinase (PI3K) inhibitors or any component of the formulations used in this study. Prior treatment with an HDAC inhibitor is not allowed (whereas prior treatment with a PI3K inhibitor is allowed). Hypersensitivity reaction to rituximab >= Grade 3 (does not apply to subjects enrolled into CUDC-907 monotherapy groups).
4. Cytotoxic anticancer therapy (e.g., alkylating agents, anti-metabolites, purine analogues) within 2 weeks of study entry.
5.Radiotherapy delivered to target lesions that will be followed on the study (note: prior sites of radiation will be recorded).
6. Treatment with experimental therapy within 5 terminal half-lives (t1/2) or 4 weeks prior to enrollment, whichever is longer.
7.Current or planned glucocorticoid therapy, with the following exceptions:
·Glucocorticoids to reduce the potential for infusion reactions to rituximab are allowed per institutional guidelines.
· Doses <= 1 mg/kg/day prednisolone or equivalent glucocorticoid and inhalational therapies for mild chronic obstructive pulmonary disease (COPD) or asthma are allowed.
·Replacement dosing of steroids (defined as < 30 mg/day hydrocortisone or the equivalent) is allowed, provided that the steroid dose has been stable or tapering for at least 14 days prior to the first dose of CUDC-907.
8. Graft versus host disease following transplant within 100 days prior to study treatment.
9. Major surgery, other than diagnostic surgery, occurring 4 weeks prior to study treatment.
10. Diabetes mellitus that is not controlled with medication.
11.Serious infection requiring intravenous antibiotic therapy within 14 days prior to study treatment.
12. Uncontrolled or severe cardiovascular disease, including myocardial infarction, unstable angina, or atrial fibrillation (AFib) within 6 months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, cardiac amyloidosis, or QTc with Fridericia’s (QTcF) correction that is unmeasurable or >= 480 msec on screening ECG (Note: for QTcF >= 480 sec on the screening ECG, the ECG may be repeated twice at least 24 hours apart; the mean QTcF from the three screening ECGs must be < 480 msec in order to meet eligibility for trial participation).
13. Gastrointestinal disease or disorder that could interfere with the swallowing, oral absorption, or tolerance of CUDC-907. This includes uncontrolled diarrhea (> 1 watery stool/day), major abdominal surgery, significant bowel obstruction and/or gastrointestinal diseases that could alter the assessment of pharmacokinetics or safety, including but not limited to: irritable bowel syndrome, ulcerative colitis, Crohn’s disease and hemorrhagic coloproctitis.
14.History o
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method