Myelodysplastic Syndrome
Conditions
Keywords
Antibody-Drug Conjugate CD33 Antigen
Brief summary
This is a phase 1/2 study to evaluate the combination of vadastuximab talirine (SGN-CD33A; 33A) and azacitidine in subjects with previously untreated International Prognostic Scoring System (IPSS) Intermediate-2 or high risk myelodysplastic syndrome (MDS).
Detailed description
In the phase 1 portion of the study, escalating doses of 33A will be evaluated in combination with azacitidine, and a dose of 33A will be selected to proceed to phase 2. The phase 2 portion of the study is randomized, double-blind and placebo-controlled; it is designed to compare the overall response rate (ORR) between 2 study arms.
Interventions
Intravenous (IV) push every 4 weeks
DRUGAzacitidine
75 mg/m\^2 given intravenously or subcutaneously for 7 days every 4 weeks
DRUGPlacebo (for 33A)
Placebo supplied in single-use vials matching 33A, IV push every 4 weeks
Sponsors
Seagen Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with cytologically/histologically confirmed MDS according to the World Health Organization (WHO) 2008 classification. * Previously untreated for Myelodysplastic Syndrome (MDS) * Age ≥18 years of age. * Eligible for therapy with azacitidine. * Life expectancy of at least 12 weeks. * Eastern Cooperative Oncology Group (ECOG) performance status ≤2. * Adequate baseline laboratory parameters.
Exclusion criteria
* Received prior treatment for MDS with lenalidomide or hypomethylating agents (HMAs). * History of one of the following myeloproliferative neoplasms: essential thrombocythemia, polycythemia vera, and primary myelofibrosis. * Second malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, eg, prostate or breast cancer). * Candidates for allogeneic stem cell transplant at the time of screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study | Up to 1 year | A recommended dose of vadastuximab talirine was not identified in Phase 1 due to study termination. Number of dose delays and reductions are reported in lieu of a dose recommendation. |
| Phase 2 Outcome Measure: Overall Response Rate for the Phase 2 Portion of the Study | N/A - End point not assessed | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic Improvement (HI) Rate | N/A - End point not assessed | Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the HI rate, as defined by the 2006 IWG criteria for MDS. |
| Duration of Response (DOR) Rate | N/A - End point not assessed | Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the time from first observation of response (CR, PR, or Marrow CR) to disease progression/relapse or death from any cause, whichever occurs first. |
| Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Up to 1 year | As defined by the number of participants with adverse events and laboratory abnormalities. Participants are included only once per row, even if the participant experienced multiple events applicable to the category. |
| Rate of Transformation to Acute Myeloid Leukemia (AML) | N/A - End point not assessed | Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the rate of transformation to AML after initiation of study therapy. |
| Overall Survival (OS) | N/A - End point not assessed | Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the time from first dose of study medication to death due to any cause. |
| Progression Free Survival (PFS) | N/A - End point not assessed | Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the time from first dose of study medication to first documentation of disease progression/relapse, or to death due to any cause, whichever occurs first. |
| Complete Response Rate (CR) | N/A - End point not assessed | Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the CR rate, as defined by the 2006 IWG criteria for MDS. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 33A (5 mcg/kg) + Azacitidine Vadastuximab talirine (33A) plus azacitidine
Vadastuximab talirine (5mcg/kg) given via intravenous (IV) push every 4 weeks
Azacitidine (75 mg/m\^2) given intravenously or subcutaneously x 7 days every 4 weeks | 13 |
| 33A (10 mcg/kg) + Azacitidine Vadastuximab talirine (33A) plus azacitidine
Vadastuximab talirine (10mcg/kg) given via intravenous (IV) push every 4 weeks
Azacitidine (75 mg/m\^2) given intravenously or subcutaneously x 7 days every 4 weeks | 6 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 8 | 0 |
| Overall Study | Study Termination by Sponsor | 4 | 6 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | 33A (10 mcg/kg) + Azacitidine | 33A (5 mcg/kg) + Azacitidine |
|---|---|---|---|
| Age, Continuous | 72 years | 66 years | 72 years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0: Normal activity | 8 Participants | 2 Participants | 6 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1: Symptoms but ambulatory | 10 Participants | 4 Participants | 6 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 2: In bed less than 50% of the time | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 6 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 5 Participants | 10 Participants |
| Region of Enrollment United States | 19 participants | 6 participants | 13 participants |
| Sex: Female, Male Female | 8 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 11 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 13 | 0 / 6 |
| other Total, other adverse events | 13 / 13 | 6 / 6 |
| serious Total, serious adverse events | 9 / 13 | 4 / 6 |
Outcome results
Primary
Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study
A recommended dose of vadastuximab talirine was not identified in Phase 1 due to study termination. Number of dose delays and reductions are reported in lieu of a dose recommendation.
Time frame: Up to 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 33A (5 mcg/kg) + Azacitidine | Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study | Azacitidine doses reduced | 2 Number of doses |
| 33A (5 mcg/kg) + Azacitidine | Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study | Vadastuximab talirine doses delayed | 2 Number of doses |
| 33A (5 mcg/kg) + Azacitidine | Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study | Vadastuximab talirine dosed reduced | 4 Number of doses |
| 33A (5 mcg/kg) + Azacitidine | Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study | Azacitidine doses delayed | 3 Number of doses |
| 33A (5 mcg/kg) + Azacitidine | Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study | Azacitidine unplanned dose adjustments | 3 Number of doses |
| 33A (10 mcg/kg) + Azacitidine | Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study | Azacitidine unplanned dose adjustments | 0 Number of doses |
| 33A (10 mcg/kg) + Azacitidine | Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study | Azacitidine doses delayed | 3 Number of doses |
| 33A (10 mcg/kg) + Azacitidine | Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study | Vadastuximab talirine doses delayed | 0 Number of doses |
| 33A (10 mcg/kg) + Azacitidine | Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study | Azacitidine doses reduced | 2 Number of doses |
| 33A (10 mcg/kg) + Azacitidine | Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study | Vadastuximab talirine dosed reduced | 1 Number of doses |
Primary
Phase 2 Outcome Measure: Overall Response Rate for the Phase 2 Portion of the Study
Time frame: N/A - End point not assessed
Population: No patients were assessed for this outcomes as the study did not progress to Phase 2.
Secondary
Complete Response Rate (CR)
Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the CR rate, as defined by the 2006 IWG criteria for MDS.
Time frame: N/A - End point not assessed
Population: No patients were assessed for this outcomes as the study did not progress to Phase 2.
Secondary
Duration of Response (DOR) Rate
Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the time from first observation of response (CR, PR, or Marrow CR) to disease progression/relapse or death from any cause, whichever occurs first.
Time frame: N/A - End point not assessed
Population: No patients were assessed for this outcomes as the study did not progress to Phase 2.
Secondary
Hematologic Improvement (HI) Rate
Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the HI rate, as defined by the 2006 IWG criteria for MDS.
Time frame: N/A - End point not assessed
Population: No patients were assessed for this outcomes as the study did not progress to Phase 2.
Secondary
Overall Survival (OS)
Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the time from first dose of study medication to death due to any cause.
Time frame: N/A - End point not assessed
Population: No patients were assessed for this outcomes as the study did not progress to Phase 2.
Secondary
Progression Free Survival (PFS)
Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the time from first dose of study medication to first documentation of disease progression/relapse, or to death due to any cause, whichever occurs first.
Time frame: N/A - End point not assessed
Population: No patients were assessed for this outcomes as the study did not progress to Phase 2.
Secondary
Rate of Transformation to Acute Myeloid Leukemia (AML)
Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the rate of transformation to AML after initiation of study therapy.
Time frame: N/A - End point not assessed
Population: No patients were assessed for this outcomes as the study did not progress to Phase 2.
Secondary
Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities
As defined by the number of participants with adverse events and laboratory abnormalities. Participants are included only once per row, even if the participant experienced multiple events applicable to the category.
Time frame: Up to 1 year
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 33A (5 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Serious TEAE | 9 Participants |
| 33A (5 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | TEAE of Grades 3-5 | 12 Participants |
| 33A (5 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Azacitidine-related TEAE | 13 Participants |
| 33A (5 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Vadatuximab talirine-related TEAE of Grades 3-5 | 9 Participants |
| 33A (5 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Vadatuximab talirine-related serious TEAE | 4 Participants |
| 33A (5 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Azacitidine-related TEAE of Grades 3-5 | 10 Participants |
| 33A (5 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Vadatuximab talirine-related TEAE | 9 Participants |
| 33A (5 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | TEAE with outcome of death | 2 Participants |
| 33A (5 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Azacitidine-related serious TEAE | 5 Participants |
| 33A (5 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Dose-limiting toxicity | 2 Participants |
| 33A (5 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Treatment-emergent adverse event (TEAE) | 13 Participants |
| 33A (10 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Dose-limiting toxicity | 0 Participants |
| 33A (10 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Treatment-emergent adverse event (TEAE) | 6 Participants |
| 33A (10 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Vadatuximab talirine-related TEAE | 6 Participants |
| 33A (10 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Azacitidine-related TEAE | 6 Participants |
| 33A (10 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Serious TEAE | 4 Participants |
| 33A (10 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Vadatuximab talirine-related serious TEAE | 4 Participants |
| 33A (10 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Azacitidine-related serious TEAE | 4 Participants |
| 33A (10 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | TEAE of Grades 3-5 | 6 Participants |
| 33A (10 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Vadatuximab talirine-related TEAE of Grades 3-5 | 6 Participants |
| 33A (10 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | Azacitidine-related TEAE of Grades 3-5 | 6 Participants |
| 33A (10 mcg/kg) + Azacitidine | Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | TEAE with outcome of death | 0 Participants |