Relapsed and/or Refractory Diffuse Large B-cell Lymphoma Including With Myc Alterations
Conditions
Keywords
DLBCL, MYC
Brief summary
This is a Phase 2, open-label, multicenter trial designed to evaluate the efficacy and safety of CUDC-907 in subjects 18 years and older with Relapsed/Refractory (RR) MYC-altered Diffuse Large B-Cell Lymphoma (DLBCL).
Detailed description
Patients with RR DLBCL will be eligible for treatment with CUDC-907, as long as they have tumor tissue available that can be tested for MYC-altered disease based on one of the following: * Fresh tumor tissue obtained from biopsy accessible lesions , or * Archived tumor tissue (most recent available) Subjects will be required to submit archival tumor samples (most recent available) or fresh tumor samples for central FISH and IHC testing. Subjects whose tumors have been previously characterized as MYC-altered are strongly encouraged to enter the study. For subjects who enter the study with unconfirmed MYC-altered disease, fresh tumor samples are preferred.
Interventions
DRUGCUDC-907
Sponsors
Curis, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 (SCT) (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, 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, and Burkitt lymphoma are not eligible.
Exclusion criteria
1. Known primary mediastinal, ocular, epidural, testicular or breast DLBCL. 2. Active CNS involvement of their malignancy. 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 ≤ 10 mg/kg/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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 2 Years | Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered Diffuse Large B-Cell Lymphoma (DLBCL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression-free Survival | 1 year | Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL |
| Overall Survival (OS) | 1 year | Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL |
| Disease Control Rate (DCR) | 1 year | Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL Note: Response is defined using Cheson 2007 criteria. CR=Complete Response; PR=Partial Response; SD=Stable Disease. a. Two-sided exact binomial 95% confidence interval. Revised Response Criteria for Malignant Lymphoma (Cheson 2007) was used for the assessment of response. DCR is defined as the proportion of patients having best response of complete response, partial response, or stable disease. |
| Number of Participants and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters | AEs were collected for each participant for the duration that they remained on the study, on average of 4 months | Number of participants and severity of adverse events (AEs), serious adverse events (SAEs), and other safety parameters in patients receiving CUDC-907. |
Countries
Spain, United States
Participant flow
Recruitment details
Adverse Events were collected from signing of the ICF through the last patient visit. (July2016 - May 2019)
Participants by arm
| Arm | Count |
|---|---|
| Group A MYC translocation+ and/or MYC gene copy number gain by FISH | 5 |
| Group B MYC expression in \> 40% of tumor cells by IHC | 49 |
| Group C MYC translocation- by FISH, and MYC expression in \< 40% of tumor cells, and no MYC gene copy number gain by FISH | 16 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 4 | 5 | 8 |
| Overall Study | Lack of Efficacy | 1 | 17 | 3 |
| Overall Study | Lost to Follow-up | 0 | 8 | 0 |
| Overall Study | Other | 0 | 8 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 7 | 1 |
Baseline characteristics
| Characteristic | Group A | Total | Group C | Group B |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 30 Participants | 8 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 40 Participants | 8 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 6 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 61 Participants | 14 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 4 Participants | 62 Participants | 14 Participants | 44 Participants |
| Region of Enrollment France | 1 participants | 6 participants | 0 participants | 5 participants |
| Region of Enrollment Spain | 0 participants | 3 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 4 participants | 61 participants | 15 participants | 42 participants |
| Sex: Female, Male Female | 2 Participants | 29 Participants | 7 Participants | 20 Participants |
| Sex: Female, Male Male | 3 Participants | 41 Participants | 9 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 17 / 68 |
| other Total, other adverse events | 68 / 68 |
| serious Total, serious adverse events | 30 / 68 |
Outcome results
Primary
Objective Response Rate (ORR)
Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered Diffuse Large B-Cell Lymphoma (DLBCL)
Time frame: 2 Years
Population: The analysis of ORR was not performed since central radiographic review was not performed, due to inconclusive efficacy at the interim analysis, enrollment was permanently stopped in August 2017.
Secondary
Disease Control Rate (DCR)
Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL Note: Response is defined using Cheson 2007 criteria. CR=Complete Response; PR=Partial Response; SD=Stable Disease. a. Two-sided exact binomial 95% confidence interval. Revised Response Criteria for Malignant Lymphoma (Cheson 2007) was used for the assessment of response. DCR is defined as the proportion of patients having best response of complete response, partial response, or stable disease.
Time frame: 1 year
Population: Evaluable population; The number of participants in this table include the evaluable participants which is different from the overall number of participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CUDC-907 | Disease Control Rate (DCR) | 0.0 percentage of participants |
| Group B | Disease Control Rate (DCR) | 46.4 percentage of participants |
| Group C | Disease Control Rate (DCR) | 44.4 percentage of participants |
Secondary
Median Progression-free Survival
Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL
Time frame: 1 year
Population: Evaluable population; The number of participants in this table include the evaluable participants which is different from the overall number of participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CUDC-907 | Median Progression-free Survival | 1.2 months |
| Group B | Median Progression-free Survival | 2.7 months |
| Group C | Median Progression-free Survival | 2.6 months |
Secondary
Number of Participants and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters
Number of participants and severity of adverse events (AEs), serious adverse events (SAEs), and other safety parameters in patients receiving CUDC-907.
Time frame: AEs were collected for each participant for the duration that they remained on the study, on average of 4 months
Population: Safety Population; The number of participants in this table include the participants evaluable for safety which is different from the overall number of participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CUDC-907 | Number of Participants and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters | Experienced at least 1 tx emergent SAE | 30 participants |
| CUDC-907 | Number of Participants and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters | Experienced a TEAE with outcome of death | 17 participants |
| CUDC-907 | Number of Participants and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters | Experienced at least 1 TEAE | 68 participants |
| CUDC-907 | Number of Participants and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters | Experienced at least 1 study tx-related TEAE | 59 participants |
| CUDC-907 | Number of Participants and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters | Experienced a Grade <3 TEAE | 52 participants |
| CUDC-907 | Number of Participants and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters | Experienced a Grade <3 TEAE tx-related | 34 participants |
| CUDC-907 | Number of Participants and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters | Experienced a TEAE leading to D/C | 11 participants |
Secondary
Overall Survival (OS)
Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL
Time frame: 1 year
Population: Evaluable population; The number of participants in this table include the evaluable participants which is different from the overall number of participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CUDC-907 | Overall Survival (OS) | 1 participants |
| Group B | Overall Survival (OS) | 17 participants |
| Group C | Overall Survival (OS) | 2 participants |