Lymphoma
Conditions
Interventions
Treatment administration:
• CUDC-907 monotherapy:
* CUDC-907 60 mg (2 × 30 mg capsules) orally (PO) for 5 days on/2 days off
(5/2) (21-day cycles).
During Treatment:
Subjects will have 4 clinic visi
Relapsed/Refractory MYC-Altered Diffuse Large B-Cell Lymphoma
Sponsors
Curis, Inc.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years. 2. At least 2 but no more than 4 prior lines of therapy for the treatment of de novo DLBCL and ineligible for (or failed) autologous or allogeneic stem cell transplant (salvage therapy, conditioning therapy and maintenance with transplant will be considered one prior treatment). NOTE: For follicular lymphoma transformed to DLBCL (t FL/DLBCL), single-agent non-cytotoxic therapy will not be considered as a line of therapy. 3. Histopathologically confirmed diagnosis of one of the following: • RR DLBCL per the 2008 World Health Organization (WHO) classification of hematopoietic and lymphoid tumors (Swerdlow et al, 2008) • High grade B-cell lymphoma (HGBL), with MYC and BCL2 and/or BCL6 rearrangements, or DLBCL, not otherwise specified (NOS), per the 2016 revision of the WHO classification of lymphoid neoplasms (Swerdlow et al, 2016). • Diagnosis of t-FL/DLBCL is allowed. However, other B-cell lymphomas including other transformed indolent lymphomas/DLBCL per the 2008 WHO classification, HGBL, NOS per the 2016 WHO classification, and Burkitt lymphoma are not eligible. 4. Confirmed availability of viable tissue (defined as most recent available archival tumor tissue, 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. NOTE: To facilitate early testing of MYC status, a separate informed consent form (ICF) specific for MYC testing will be available to be signed prior to sample testing and the signing of the main ICF. 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 = 3 cycles of prior treatment, or (c) partial response (PR) after >= 6 cycles of prior treatment, or for stage II disease, >= 3 cycles of treatment and definitive involved field radiotherapy. o For sustained PR after prior 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 prior 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. Recovery to Grade 1 or baseline of any toxicity due to prior anticancer therapies (excluding alopecia). 9. Absolute neu
Exclusion criteria
Exclusion criteria: 1. Known primary mediastinal, ocular, epidural, testicular or breast DLBCL. 2. 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 phosphatidylinositol 3 kinase (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 = 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 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 of other invasive malignancy, unless adequately treated with curative intent and with no known active disease present within 1 year prior to the first dose of study drug, provided it is deemed to be at low risk for recurrence by the treating physician. • These conditions include but are not limited to non-melanoma skin cancer, carcinoma in situ, (including superficial bladder cancer), cervical intraepithelial neoplasia and organ-confined prostate cancer. 15.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the efficacy of CUDC-907 as measured by the objective response rate (ORR) in Group B subjects with relapsed and/or refractory (RR) diffuse large B-cell lymphoma (DLBCL) with MYC-altered disease by immunohistochemistry (IHC). | — |
Secondary
| Measure | Time frame |
|---|---|
| • To evaluate ORR (central and local determination) in Group B subjects • To evaluate progression-free survival (PFS), median PFS, and PFS at 6 months (PFS6) in Group B subjects. • To evaluate overall survival (OS) in Group B subjects. • To evaluate the disease control rate (DCR) and duration of response (DOR) in Group B subjects. • To evaluate ORR in Group A and C subjects • To evaluate the incidence and severity of adverse events (AEs), serious adverse events (SAEs), and other safety parameters in subjects receiving CUDC-907. • To characterize the pharmacokinetics (PK) of CUDC-907 alone. | — |
Countries
France, Germany, Netherlands, Spain, United States of America
Outcome results
None listed