Trial Outcomes & Findings for Temozolomide Plus Vorinostat in Relapse/Refractory Acute Myeloid Leukemia (AML) (NCT NCT01550224)
NCT ID: NCT01550224
Last Updated: 2018-08-09
Results Overview
This study evaluates the clinical efficacy of temozolomide + vorinostat as administered to Groups 1 and 2, assessed as the rate of complete remission \[CR, aka morphologic complete remission (mCR)\], defined as the morphologic leukemia-free state (MLFS), WITH absolute neutrophil count (ANC) ≥ 1,000/µL AND platelets (PLT) ≥ 100,000/µL. The outcome is reported as the percentage without dispersion of participants in Groups 1 and 2 that demonstrated CR. CR is defined as all of the following. MLFS = \< 5% blasts in bone marrow aspirate containing marrow spicules \> 200 nucleated cells no blasts with Auer rods no persistence of extramedullary disease ANC = ≥ 1,000/µL PLT = ≥ 100,000/µL
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
23 participants
Primary outcome timeframe
up to 10 weeks
Results posted on
2018-08-09
Participant Flow
Participant milestones
| Measure |
Participant Group 1 (Methylated MGMT Promoter)
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days. Group 2 participants also receive at protracted, pre-induction treatment with 100 mg/m²/day for 14 days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Participant Group 2 (Non-methylated MGMT Promoter)
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
|---|---|---|
|
Overall Study
STARTED
|
3
|
20
|
|
Overall Study
COMPLETED
|
3
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Temozolomide Plus Vorinostat in Relapse/Refractory Acute Myeloid Leukemia (AML)
Baseline characteristics by cohort
| Measure |
Participant Group 1 (Methylated MGMT Promoter)
n=3 Participants
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days. Group 2 participants also receive at protracted, pre-induction treatment with 100 mg/m²/day for 14 days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Participant Group 2 (Non-methylated MGMT Promoter)
n=20 Participants
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Age, Continuous
|
76.3 years
n=5 Participants
|
83 years
n=7 Participants
|
82.7 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
20 participants
n=7 Participants
|
23 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to 10 weeksThis study evaluates the clinical efficacy of temozolomide + vorinostat as administered to Groups 1 and 2, assessed as the rate of complete remission \[CR, aka morphologic complete remission (mCR)\], defined as the morphologic leukemia-free state (MLFS), WITH absolute neutrophil count (ANC) ≥ 1,000/µL AND platelets (PLT) ≥ 100,000/µL. The outcome is reported as the percentage without dispersion of participants in Groups 1 and 2 that demonstrated CR. CR is defined as all of the following. MLFS = \< 5% blasts in bone marrow aspirate containing marrow spicules \> 200 nucleated cells no blasts with Auer rods no persistence of extramedullary disease ANC = ≥ 1,000/µL PLT = ≥ 100,000/µL
Outcome measures
| Measure |
Participant Group 1 (Methylated MGMT Promoter)
n=3 Participants
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days. Group 2 participants also receive at protracted, pre-induction treatment with 100 mg/m²/day for 14 days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Participant Group 2 (Non-methylated MGMT Promoter)
n=20 Participants
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
|---|---|---|
|
Complete Remission (CR)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to 10 weeksThe rate of morphologic leukemia-free state (MLFS) is reported as the percentage without dispersion of participants in Groups 1 and 2 that achieve MLFS. The outcome is reported as the percentage without dispersion of participants in Groups 1 and 2 that demonstrated MLFS. This assessment is independent of absolute neutrophil count (ANC) or platelets (PLT) recovery status. MLFS is defined below. MLFS = \< 5% blasts in bone marrow aspirate containing marrow spicules \> 200 nucleated cells no blasts with Auer rods no persistence of extramedullary disease
Outcome measures
| Measure |
Participant Group 1 (Methylated MGMT Promoter)
n=3 Participants
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days. Group 2 participants also receive at protracted, pre-induction treatment with 100 mg/m²/day for 14 days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Participant Group 2 (Non-methylated MGMT Promoter)
n=20 Participants
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
|---|---|---|
|
Morphologic Leukemia-free State (MLFS)
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: up to 10 weeksThe rate of complete remission with incomplete blood count recovery (CRp) for Groups 1 and 2 was assessed as the rate of morphologic leukemia-free state (MLFS) but with EITHER residual neutropenia (ANC \< 1,000/µL) OR residual thrombocytopenia (PLT \< 100,000/µL). MLFS is defined as follows. MLFS = \< 5% blasts in bone marrow aspirate containing marrow spicules \> 200 nucleated cells no blasts with Auer rods no persistence of extramedullary disease
Outcome measures
| Measure |
Participant Group 1 (Methylated MGMT Promoter)
n=3 Participants
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days. Group 2 participants also receive at protracted, pre-induction treatment with 100 mg/m²/day for 14 days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Participant Group 2 (Non-methylated MGMT Promoter)
n=20 Participants
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
|---|---|---|
|
Complete Remission With Incomplete Blood Count Recovery (CRp)
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: up to 10 weeksCytogenetic response (CyR) is defined as complete remission (CR), PLUS a documented decrease or absence of cytogenetic abnormalities, when analyzed microscopically for 20 cellular metaphases (actively dividing cells). The outcome is reported as the percentage without dispersion of participants in Groups 1 and 2 that demonstrated CyR. CR is defined as all of the following. CR = \< 5% blasts in bone marrow aspirate containing marrow spicules; \> 200 nucleated cells no blasts with Auer rods; no persistence of extramedullary disease absolute neutrophil count (ANC) ≥ 1,000/µL platelets (PLT) ≥ 100,000/µL
Outcome measures
| Measure |
Participant Group 1 (Methylated MGMT Promoter)
n=3 Participants
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days. Group 2 participants also receive at protracted, pre-induction treatment with 100 mg/m²/day for 14 days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Participant Group 2 (Non-methylated MGMT Promoter)
n=20 Participants
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
|---|---|---|
|
Cytogenetic Response (CyR)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to 10 weeksPartial remission (PR) is reported as the percentage without dispersion of participants in Groups 1 and 2 that demonstrated PR. PR is defined as all of the following. PR = 5% to 25% blasts (must be ≥ 50% reduction of blasts) in bone marrow aspirate containing marrow spicules; \> 200 nucleated cells no blasts with Auer rods no persistence of extramedullary disease absolute neutrophil count (ANC) ≥ 1,000/µL platelets (PLT) ≥ 100,000/µL
Outcome measures
| Measure |
Participant Group 1 (Methylated MGMT Promoter)
n=3 Participants
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days. Group 2 participants also receive at protracted, pre-induction treatment with 100 mg/m²/day for 14 days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Participant Group 2 (Non-methylated MGMT Promoter)
n=20 Participants
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
|---|---|---|
|
Partial Remission (PR)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to 10 weeksTreatment failure (TF) is defined as failing to achieve either a complete remission (CR) or partial remission (PR) after induction chemotherapy. The outcome is reported as the percentage without dispersion of participants in Groups 1 and 2 that experienced TF. CR and PR are defined as the following. CR = \< 5% blasts in bone marrow aspirate containing marrow spicules; \> 200 nucleated cells no blasts with Auer rods; no persistence of extramedullary disease absolute neutrophil count (ANC) ≥ 1,000/µL platelets (PLT) ≥ 100,000/µL PR = 5% to 25% blasts (must be ≥ 50% reduction of blasts) in bone marrow aspirate containing marrow spicules; \> 200 nucleated cells no blasts with Auer rods no persistence of extramedullary disease absolute neutrophil count (ANC) ≥ 1,000/µL platelets (PLT) ≥ 100,000/µL
Outcome measures
| Measure |
Participant Group 1 (Methylated MGMT Promoter)
n=3 Participants
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days. Group 2 participants also receive at protracted, pre-induction treatment with 100 mg/m²/day for 14 days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Participant Group 2 (Non-methylated MGMT Promoter)
n=20 Participants
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
|---|---|---|
|
Treatment Failure (TF)
|
3 Participants
|
20 Participants
|
SECONDARY outcome
Timeframe: 2 yearsDisease-Free Survival (DFS) is defined as survival after complete response (CR) without disease progression. DFS is reported as the percentage without dispersion of participants in Groups 1 and 2 that experienced CR and were alive without progression (ie, without disease) 2 years after induction chemotherapy. CR is defined as all of the following. CR = \< 5% blasts in bone marrow aspirate containing marrow spicules; \> 200 nucleated cells no blasts with Auer rods; no persistence of extramedullary disease absolute neutrophil count (ANC) ≥ 1,000/µL platelets (PLT) ≥ 100,000/µL
Outcome measures
| Measure |
Participant Group 1 (Methylated MGMT Promoter)
n=3 Participants
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days. Group 2 participants also receive at protracted, pre-induction treatment with 100 mg/m²/day for 14 days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Participant Group 2 (Non-methylated MGMT Promoter)
n=20 Participants
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
|---|---|---|
|
Disease-free Survival (DFS) at 2 Years
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 2 yearsRelapse-free survival (RFS) is defined as survival after complete response (CR) or (PR) without further disease progression. RFS is reported as the percentage without dispersion of participants in Groups 1 and 2 that experienced CR or PR, and were alive without progression 2 years after induction chemotherapy. CR and PR are defined as the following. CR = \< 5% blasts in bone marrow aspirate containing marrow spicules; \> 200 nucleated cells no blasts with Auer rods; no persistence of extramedullary disease absolute neutrophil count (ANC) ≥ 1,000/µL platelets (PLT) ≥ 100,000/µL PR = 5% to 25% blasts (must be ≥ 50% reduction of blasts) in bone marrow aspirate containing marrow spicules; \> 200 nucleated cells no blasts with Auer rods no persistence of extramedullary disease absolute neutrophil count (ANC) ≥ 1,000/µL platelets (PLT) ≥ 100,000/µL
Outcome measures
| Measure |
Participant Group 1 (Methylated MGMT Promoter)
n=3 Participants
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days. Group 2 participants also receive at protracted, pre-induction treatment with 100 mg/m²/day for 14 days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Participant Group 2 (Non-methylated MGMT Promoter)
n=20 Participants
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
|---|---|---|
|
Relapse-Free Survival (RFS) at 2 Years
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 2 yearsOverall Survival (OS) is defined as survival regardless of clinical status. OS is reported as the percentage without dispersion of participants in Groups 1 and 2 that remained alive 2 years after induction chemotherapy.
Outcome measures
| Measure |
Participant Group 1 (Methylated MGMT Promoter)
n=3 Participants
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days. Group 2 participants also receive at protracted, pre-induction treatment with 100 mg/m²/day for 14 days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Participant Group 2 (Non-methylated MGMT Promoter)
n=20 Participants
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
|---|---|---|
|
Overall Survival (OS) at 2 Years
|
0 Participants
|
0 Participants
|
Adverse Events
Participant Group 1 (Methylated MGMT Promoter)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 3 deaths
Participant Group 2 (Non-methylated MGMT Promoter)
Serious events: 11 serious events
Other events: 20 other events
Deaths: 20 deaths
Serious adverse events
| Measure |
Participant Group 1 (Methylated MGMT Promoter)
n=3 participants at risk
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days. Group 2 participants also receive at protracted, pre-induction treatment with 100 mg/m²/day for 14 days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Participant Group 2 (Non-methylated MGMT Promoter)
n=20 participants at risk
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3 • 2 years
|
10.0%
2/20 • Number of events 3 • 2 years
|
|
Vascular disorders
Hemorrhage (bleeding), subdural hematoma
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Infections and infestations
Infection - E coli bacteremia
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Infections and infestations
Infection - neutropenic fever
|
0.00%
0/3 • 2 years
|
20.0%
4/20 • Number of events 4 • 2 years
|
|
Infections and infestations
Infection - pneumonia
|
0.00%
0/3 • 2 years
|
15.0%
3/20 • Number of events 3 • 2 years
|
|
Infections and infestations
Infection - Sepsis
|
0.00%
0/3 • 2 years
|
10.0%
2/20 • Number of events 2 • 2 years
|
|
Investigations
Thrombocytopenia (platelet count decreased)
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Hemoptysis (coughing up blood)
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
Other adverse events
| Measure |
Participant Group 1 (Methylated MGMT Promoter)
n=3 participants at risk
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days. Group 2 participants also receive at protracted, pre-induction treatment with 100 mg/m²/day for 14 days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
Participant Group 2 (Non-methylated MGMT Promoter)
n=20 participants at risk
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Temozolomide: An alkylating agent administered for induction per standard of care at 200 mg/m²/day for 7days.
Vorinostat: A synthetic hydroxamic acid derivative with antineoplastic activity administered for both groups at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
|
|---|---|---|
|
Renal and urinary disorders
Hematuria (blood in urine)
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Blood and lymphatic system disorders
Anemia (reduced level of red blood cells)
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Blood and lymphatic system disorders
Leukopenia (reduced level of white blood cells)
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Blood and lymphatic system disorders
Low hemoglobin
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Blood and lymphatic system disorders
Neutropenia (reduced level of neutrophils)
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Blood and lymphatic system disorders
Neutropenic fever
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/20 • 2 years
|
|
Blood and lymphatic system disorders
Pancytopenia (reduced level of many or all blood cells)
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Blood and lymphatic system disorders
Thrombocytopenia (reduced level of platlets)
|
0.00%
0/3 • 2 years
|
25.0%
5/20 • Number of events 5 • 2 years
|
|
Cardiac disorders
Arrhythmia (irregular heart beat)
|
0.00%
0/3 • 2 years
|
10.0%
2/20 • Number of events 2 • 2 years
|
|
Cardiac disorders
Hypotension (low blood pressure)
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Abdominal or epigastric discomfort
|
0.00%
0/3 • 2 years
|
10.0%
2/20 • Number of events 2 • 2 years
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Cough
|
0.00%
0/3 • 2 years
|
25.0%
5/20 • Number of events 5 • 2 years
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
1/3 • Number of events 1 • 2 years
|
45.0%
9/20 • Number of events 9 • 2 years
|
|
Gastrointestinal disorders
Dysphagia (difficulty swallowing)
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Loss of appetite
|
66.7%
2/3 • Number of events 2 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Melena (blood in stool)
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Nausea
|
66.7%
2/3 • Number of events 2 • 2 years
|
40.0%
8/20 • Number of events 8 • 2 years
|
|
Gastrointestinal disorders
Rectal abscess
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Vomiting
|
66.7%
2/3 • Number of events 2 • 2 years
|
35.0%
7/20 • Number of events 7 • 2 years
|
|
General disorders
Back pain
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
General disorders
Dysgeusia (altered sense of taste)
|
0.00%
0/3 • 2 years
|
10.0%
2/20 • Number of events 2 • 2 years
|
|
General disorders
Elevated serum lactase
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
General disorders
Fatigue
|
66.7%
2/3 • Number of events 2 • 2 years
|
50.0%
10/20 • Number of events 10 • 2 years
|
|
General disorders
Limb edema (swelling in extremities)
|
0.00%
0/3 • 2 years
|
15.0%
3/20 • Number of events 3 • 2 years
|
|
General disorders
Maceration
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
General disorders
Night sweat
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
General disorders
Skin infection (boil)
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
General disorders
Weakness
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
General disorders
Weight loss
|
0.00%
0/3 • 2 years
|
10.0%
2/20 • Number of events 2 • 2 years
|
|
Nervous system disorders
Altered mental status (confusion)
|
0.00%
0/3 • 2 years
|
10.0%
2/20 • Number of events 2 • 2 years
|
|
Nervous system disorders
Insomnia (inability to sleep)
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Nervous system disorders
Lethargic
|
0.00%
0/3 • 2 years
|
10.0%
2/20 • Number of events 2 • 2 years
|
|
Nervous system disorders
Metabolic encephalopathy
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Nervous system disorders
Vertigo (dizziness or syncope)
|
0.00%
0/3 • 2 years
|
20.0%
4/20 • Number of events 4 • 2 years
|
|
Renal and urinary disorders
Difficulty urinating
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress
|
0.00%
0/3 • 2 years
|
10.0%
2/20 • Number of events 2 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Chest pain
|
0.00%
0/3 • 2 years
|
10.0%
2/20 • Number of events 2 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Chills
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Difficulty of breathing
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
33.3%
1/3 • Number of events 1 • 2 years
|
20.0%
4/20 • Number of events 4 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis (nosebleed)
|
33.3%
1/3 • Number of events 1 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Fever
|
66.7%
2/3 • Number of events 2 • 2 years
|
10.0%
2/20 • Number of events 2 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
33.3%
1/3 • Number of events 1 • 2 years
|
10.0%
2/20 • Number of events 2 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
0.00%
0/3 • 2 years
|
0.00%
0/20 • 2 years
|
|
Skin and subcutaneous tissue disorders
Petechiae (skin spots)
|
0.00%
0/3 • 2 years
|
25.0%
5/20 • Number of events 5 • 2 years
|
|
Skin and subcutaneous tissue disorders
Pruritus (itching)
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/3 • 2 years
|
5.0%
1/20 • Number of events 1 • 2 years
|
Additional Information
Steven Edward Coutre, MD; Professor of Medicine (Hematology)
Stanford University Medical Center
Phone: 650-725-4040
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place