Study to Evaluate how safe and how effective is CUDC-907 in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma, Including Patients With MYC Alterations
- Conditions
- Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma including patients with MYC alterationsMedDRA version: 21.0 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: 21.0 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-DE
- Lead Sponsor
- Curis, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 200
1. Age = 18 years.
2. At least two but no more than 4 prior lines of therapy for treatment of de novo DLBCL and ineligible for (or failed) autologous or allogeneic SCT (salvage therapy, conditioning therapy and maintenance with transplant will be considered one prior treatment).
3. Histopathologically confirmed diagnosis of one of the following:
- RR DLBCL per the 2008 WHO classification of hematopoietic and
lymphoid tumors
- HGBL, with MYC and BCL2 and/or BCL6 rearrangements or DLBCL, NOS per the 2016 revision of the WHO classification of lymphoid neoplasms.
- Diagnosis of t-FL DLBCL is allowed. However, other B-cell lymphomas
including B-cell lymphoma/DLBCL unclassifiable with features
intermediate between DLBCL, per the 2008 WHO classification, HGBL,
NOS per the 2016 WHO classification, and Burkitt are not eligible.
4. Confirmed availability of viable tissue (defined as most recent
available archival tumor tissue available or fresh tumor samples) for
central laboratory FISH and IHC testing and review prior to study
dosing. Previously decalcified samples are not appropriate for FISH
testing. Therefore bone marrow samples are not acceptable. For subjects who enter the study with unconfirmed MYC-altered disease, fresh tumor samples are preferred.
5. 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. All lesions must have a maximum diameter of < 10 cm.
Baseline FDG-PET scans, if used, must demonstrate positive lesions
compatible with CT-defined anatomical tumor sites.
6. Presence of RR disease per Revised Response Criteria for Malignant
Lymphoma.
· Relapsed disease is defined by DLBCL confirmed by
excisional/incisional biopsy (preferred) or fine needle aspiration
(FNA) or core needle biopsy (CNB) after a 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) 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.
7. Eastern Cooperative Oncology Group (ECOG) performance status of =
1.
8. Rec
1. Known primary mediastinal, ocular, epidural, testicular or breast
DLBCL.
2. Patients must not have active CNS involvement of their malignancy.
Patients with prior brain metastases are permitted, but must have
completed treatment and have no evidence of active CNS disease (clear
cerebrospinal fluid [CSF]) for at least 4 weeks prior to the first dose of
CUDC-907. Intrathecal chemoprophylaxis to prevent the emergence or
recurrence of lymphoma in the CNS is permitted on study and may be
administered per institutional guidelines.
3. Known allergy or hypersensitivity to PI3K inhibitors or any component
of the formulations used in this study.
4. Cytotoxic anticancer therapy (e.g., alkylating agents, anti-metabolites, purine analogues) or any other systemic anticancer therapy within 2 weeks of study entry.
5. Radiotherapy delivered to non-target lesions within one week prior to starting study treatment or 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 :
- Doses = 10 mg/day prednisolone or 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.
- Inhaled, intranasal, intraarticular, and topical steroids are permitted
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 electtrocardiogram 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 a
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