Trial Outcomes & Findings for Investigation of [6R] 5,10-methylenetetrahydrofolate (Arfolitixorin) as Rescue Therapy for Osteosarcoma Patients Treated With HDMTX. (NCT NCT01987102)
NCT ID: NCT01987102
Last Updated: 2020-09-25
Results Overview
Characterization (number and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
18 participants
Primary outcome timeframe
From the start of HDMTX administration through 8 days post dose for each course of HDMTX in total
Results posted on
2020-09-25
Participant Flow
Patients were pre-screened for eligibility to participate by the principal investigator among those patients who have received confirmed diagnosis of osteosarcoma and were planned for surgical resection of their tumor in combination with neoadjuvant or adjuvant chemotherapy.
Participant milestones
| Measure |
Cohort 1
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
2 Courses of HDMTX With SOC Rescue
STARTED
|
8
|
10
|
|
2 Courses of HDMTX With SOC Rescue
COMPLETED
|
4
|
4
|
|
2 Courses of HDMTX With SOC Rescue
NOT COMPLETED
|
4
|
6
|
|
2 Courses of HDMTX With MOD Rescue
STARTED
|
4
|
4
|
|
2 Courses of HDMTX With MOD Rescue
COMPLETED
|
4
|
3
|
|
2 Courses of HDMTX With MOD Rescue
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Cohort 1
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
2 Courses of HDMTX With SOC Rescue
Adverse Event
|
2
|
2
|
|
2 Courses of HDMTX With SOC Rescue
Laboratory abnormality
|
1
|
2
|
|
2 Courses of HDMTX With SOC Rescue
Change in planned chemotherapy
|
1
|
0
|
|
2 Courses of HDMTX With SOC Rescue
Protocol Violation
|
0
|
1
|
|
2 Courses of HDMTX With SOC Rescue
Incorrectly included
|
0
|
1
|
|
2 Courses of HDMTX With MOD Rescue
Adverse Event
|
0
|
1
|
Baseline Characteristics
Investigation of [6R] 5,10-methylenetetrahydrofolate (Arfolitixorin) as Rescue Therapy for Osteosarcoma Patients Treated With HDMTX.
Baseline characteristics by cohort
| Measure |
Cohort 1
n=8 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=10 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
Czechia
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From the start of HDMTX administration through 8 days post dose for each course of HDMTX in totalPopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
Characterization (number and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Number of AEs Per Severity (All Courses)
Grade 1
|
40 Number of AEs
|
27 Number of AEs
|
|
Number of AEs Per Severity (All Courses)
Grade 2
|
8 Number of AEs
|
15 Number of AEs
|
|
Number of AEs Per Severity (All Courses)
Grade 3
|
11 Number of AEs
|
6 Number of AEs
|
|
Number of AEs Per Severity (All Courses)
Grade 4
|
3 Number of AEs
|
1 Number of AEs
|
PRIMARY outcome
Timeframe: From the start of HDMTX administration through 8 days post dose for each course of HDMTX in totalPopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Number of HDMTX Related AEs Per Severity (All Courses)
Grade 1
|
25 Number of AEs
|
20 Number of AEs
|
|
Number of HDMTX Related AEs Per Severity (All Courses)
Grade 2
|
6 Number of AEs
|
12 Number of AEs
|
|
Number of HDMTX Related AEs Per Severity (All Courses)
Grade 3
|
6 Number of AEs
|
5 Number of AEs
|
|
Number of HDMTX Related AEs Per Severity (All Courses)
Grade 4
|
1 Number of AEs
|
1 Number of AEs
|
PRIMARY outcome
Timeframe: From the start of HDMTX administration through 8 days post dose for each course of HDMTXPopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Number of Ongoing AEs Per HDMTX Course
Course 1 (SOC)
|
14 Number of AEs
|
10 Number of AEs
|
|
Number of Ongoing AEs Per HDMTX Course
Course 2 (SOC)
|
19 Number of AEs
|
10 Number of AEs
|
|
Number of Ongoing AEs Per HDMTX Course
Course 1 (MOD)
|
6 Number of AEs
|
10 Number of AEs
|
|
Number of Ongoing AEs Per HDMTX Course
Course 2 (MOD)
|
14 Number of AEs
|
16 Number of AEs
|
PRIMARY outcome
Timeframe: From the start of HDMTX administration through 8 days post dose for each course of HDMTXPopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
Characterization (frequency and severity grade) of toxicity reported for each course of HDMTX treatment with folate rescue therapy and continuing until eight (8) days after start of HDMTX administration, per NCI CTCAE v4.0 (Grade refers to the severity of the AE). The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Number of Ongoing HDMTX Related AEs Per HDMTX Course
Course 1 (SOC)
|
13 Number of AEs
|
8 Number of AEs
|
|
Number of Ongoing HDMTX Related AEs Per HDMTX Course
Course 2 (SOC)
|
13 Number of AEs
|
8 Number of AEs
|
|
Number of Ongoing HDMTX Related AEs Per HDMTX Course
Course 1 (MOD)
|
5 Number of AEs
|
10 Number of AEs
|
|
Number of Ongoing HDMTX Related AEs Per HDMTX Course
Course 2 (MOD)
|
12 Number of AEs
|
16 Number of AEs
|
SECONDARY outcome
Timeframe: 8 days after start of first and/or second HDMTX course in a MAP cyclePopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
Definition A: Successful advancement from 1st to 2nd HDMTX course within the same MAP cycle. Fulfilling all of the following criteria 8 days after start of first HDMTX course within the same MAP cycle: 1. Serum MTX: ≤0.1μmol/L 2. Neutrophils: ≥0.25x109/L 3. Platelets: ≥50x109/L 4. Serum bilirubin: ≤1.25 x upper limit of normal (ULN) 5. Glomerular filtration rate (GFR) ≥70 mL/min/1.73m2 6. No AE Grade 2 or more related to HDMTX hindering a potential HDMTX administration, at the discretion of the investigator Definition B: Successful advancement to next MAP cycle Fulfilling all of the following criteria 8 days after start of the second HDMTX course in previous MAP cycle: 1. Serum MTX: ≤0.1μmol/L 2. Neutrophils: ≥ 0.75 x 109/L 3. Platelets: ≥75x109/L 4. Serum bilirubin: ≤1.25xULN 5. GFR ≥70 mL/min/1.73m2 6. No AE Grade 2 or more related to HDMTX hindering a potential Adriamycin/Doxorubicin and Cisplatin (AP) administration, at the discretion of the investigator
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Number of Administered HDMTX Courses Classified as Having Met the Criteria for Successful Advancement According to Definition A and/or Definition B
Successful Course SOC 1
|
4 Number of courses
|
4 Number of courses
|
|
Number of Administered HDMTX Courses Classified as Having Met the Criteria for Successful Advancement According to Definition A and/or Definition B
Unsuccessful Course SOC 1
|
0 Number of courses
|
0 Number of courses
|
|
Number of Administered HDMTX Courses Classified as Having Met the Criteria for Successful Advancement According to Definition A and/or Definition B
Successful Course SOC 2
|
4 Number of courses
|
4 Number of courses
|
|
Number of Administered HDMTX Courses Classified as Having Met the Criteria for Successful Advancement According to Definition A and/or Definition B
Unsuccessful Course MOD 1
|
0 Number of courses
|
1 Number of courses
|
|
Number of Administered HDMTX Courses Classified as Having Met the Criteria for Successful Advancement According to Definition A and/or Definition B
Successful Course MOD 2
|
4 Number of courses
|
2 Number of courses
|
|
Number of Administered HDMTX Courses Classified as Having Met the Criteria for Successful Advancement According to Definition A and/or Definition B
Unsuccessful Course MOD 2
|
0 Number of courses
|
1 Number of courses
|
|
Number of Administered HDMTX Courses Classified as Having Met the Criteria for Successful Advancement According to Definition A and/or Definition B
Unsuccessful Course SOC 2
|
0 Number of courses
|
0 Number of courses
|
|
Number of Administered HDMTX Courses Classified as Having Met the Criteria for Successful Advancement According to Definition A and/or Definition B
Successful Course MOD 1
|
4 Number of courses
|
3 Number of courses
|
SECONDARY outcome
Timeframe: 8 days after start of first HDMTX course in a MAP cyclePopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
Definition A: Successful advancement from first to second HDMTX course within the same MAP cycle Fulfilling all of the following criteria 8 days after start of first HDMTX course within the same MAP cycle: 1. Serum MTX: ≤ 0.1 μmol/L 2. Neutrophils: ≥ 0.25 x 109/L 3. Platelets: ≥ 50 x 109/L 4. Serum bilirubin: ≤ 1.25 x ULN 5. GFR ≥ 70 mL/min/1.73 m2 6. No AE Grade 2 or more (NCI CTCAE v4.0) related to HDMTX hindering a potential HDMTX administration, at the discretion of the investigator
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement From First to Second HDMTX Course Within the Same MAP Cycle According to Definition A.
Successful Course SOC 1
|
4 Number of courses
|
4 Number of courses
|
|
Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement From First to Second HDMTX Course Within the Same MAP Cycle According to Definition A.
Unsuccessful Course SOC 1
|
0 Number of courses
|
0 Number of courses
|
|
Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement From First to Second HDMTX Course Within the Same MAP Cycle According to Definition A.
Successful Course MOD 1
|
4 Number of courses
|
3 Number of courses
|
|
Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement From First to Second HDMTX Course Within the Same MAP Cycle According to Definition A.
Unsuccessful Course MOD 1
|
0 Number of courses
|
1 Number of courses
|
SECONDARY outcome
Timeframe: 8 days after start of second HDMTX course in a MAP cyclePopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
Definition B: Successful advancement to next MAP cycle Fulfilling all of the following criteria 8 days after start of the second HDMTX course in previous MAP cycle: 1. Serum MTX: ≤ 0.1 μmol/L 2. Neutrophils: ≥ 0.75 x 109/L 3. Platelets: ≥ 75 x 109/L 4. Serum bilirubin: ≤ 1.25 x ULN 5. GFR ≥ 70 mL/min/1.73 m2 6. No AE Grade 2 or more (NCI CTCAE v4.0) related to HDMTX hindering a potential Adriamycin/Doxorubicin and Cisplatin (AP) administration, at the discretion of the investigator
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement to Next MAP Cycle According to Definition B.
Unsuccessful Course SOC 2
|
0 Number of courses
|
0 Number of courses
|
|
Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement to Next MAP Cycle According to Definition B.
Successful Course MOD 2
|
4 Number of courses
|
2 Number of courses
|
|
Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement to Next MAP Cycle According to Definition B.
Successful Course SOC 2
|
4 Number of courses
|
4 Number of courses
|
|
Number of Administered MAP Cycles Classified as Having Met the Criteria for Successful Advancement to Next MAP Cycle According to Definition B.
Unsuccessful Course MOD 2
|
0 Number of courses
|
1 Number of courses
|
SECONDARY outcome
Timeframe: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/LPopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
Definition C: Time to successful MTX elimination = Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/L
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Time to Successful MTX Elimination (Definition C)
Time (h) Course SOC 1
|
84.52 hours
Standard Deviation 15.00
|
62.75 hours
Standard Deviation 3.21
|
|
Time to Successful MTX Elimination (Definition C)
Time (h) Course SOC 2
|
77.0 hours
Standard Deviation 19.60
|
62.75 hours
Standard Deviation 9.91
|
|
Time to Successful MTX Elimination (Definition C)
Time (h) Course MOD 1
|
74.00 hours
Standard Deviation 15.87
|
65.75 hours
Standard Deviation 11.50
|
|
Time to Successful MTX Elimination (Definition C)
Time (h) Course MOD 2
|
72.50 hours
Standard Deviation 15.78
|
88.0 hours
Standard Deviation 43.41
|
SECONDARY outcome
Timeframe: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/LPopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Number of HDMTX Courses in Which the Initial Hydration Was Increased
Unchanged hydration Course MOD 1
|
2 HDMTX courses
|
2 HDMTX courses
|
|
Number of HDMTX Courses in Which the Initial Hydration Was Increased
Hydration change in course MOD 2
|
2 HDMTX courses
|
1 HDMTX courses
|
|
Number of HDMTX Courses in Which the Initial Hydration Was Increased
Unchanged hydration Course MOD 2
|
2 HDMTX courses
|
2 HDMTX courses
|
|
Number of HDMTX Courses in Which the Initial Hydration Was Increased
Hydration change in Course SOC 1
|
2 HDMTX courses
|
0 HDMTX courses
|
|
Number of HDMTX Courses in Which the Initial Hydration Was Increased
Unchanged hydration Course SOC 1
|
2 HDMTX courses
|
4 HDMTX courses
|
|
Number of HDMTX Courses in Which the Initial Hydration Was Increased
Hydration change in Course SOC 2
|
1 HDMTX courses
|
0 HDMTX courses
|
|
Number of HDMTX Courses in Which the Initial Hydration Was Increased
Unchanged hydration Course SOC 2
|
3 HDMTX courses
|
4 HDMTX courses
|
|
Number of HDMTX Courses in Which the Initial Hydration Was Increased
Hydration change in Course MOD 1
|
2 HDMTX courses
|
2 HDMTX courses
|
SECONDARY outcome
Timeframe: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/LPopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
Definition D: Delayed MTX elimination (according to COGs excretion toxicity management instructions) S-MTX levels of: \> 10 μmol/L at 24 h after start of MTX administration, OR \> 1 μmol/L at 48 h after start of MTX administration, OR \> 0.1 μmol/L at 72 h after start of MTX administration or later
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Number of HDMTX Courses With Delayed MTX Elimination (Definition D).
Delayed MTX elimination in Course SOC 1
|
3 Number of courses
|
0 Number of courses
|
|
Number of HDMTX Courses With Delayed MTX Elimination (Definition D).
Undelayed MTX elimination in Course SOC 1
|
1 Number of courses
|
4 Number of courses
|
|
Number of HDMTX Courses With Delayed MTX Elimination (Definition D).
Delayed MTX elimination in Course SOC 2
|
3 Number of courses
|
1 Number of courses
|
|
Number of HDMTX Courses With Delayed MTX Elimination (Definition D).
Undelayed MTX elimination in Course SOC 2
|
1 Number of courses
|
3 Number of courses
|
|
Number of HDMTX Courses With Delayed MTX Elimination (Definition D).
Delayed MTX elimination in Course MOD 1
|
2 Number of courses
|
1 Number of courses
|
|
Number of HDMTX Courses With Delayed MTX Elimination (Definition D).
Undelayed MTX elimination in Course MOD 1
|
2 Number of courses
|
3 Number of courses
|
|
Number of HDMTX Courses With Delayed MTX Elimination (Definition D).
Delayed MTX elimination in Course MOD 2
|
2 Number of courses
|
1 Number of courses
|
|
Number of HDMTX Courses With Delayed MTX Elimination (Definition D).
Undelayed MTX elimination in Course MOD 2
|
2 Number of courses
|
2 Number of courses
|
SECONDARY outcome
Timeframe: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/LPopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
Definition E: Delayed early MTX elimination (according to US label for Calcium Folinate) S-MTX levels of: * 50 μmol/L at 24 hours after start of MTX administration, OR * 5 μmol/L at 48 hours after start of MTX administration OR An increase in S-Creatinine level of 100% or greater at 24 hours after start of MTX administration.
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Number of HDMTX Courses With Delayed Early MTX Elimination (Definition E).
Delayed early MTX elimination in Course SOC 1
|
0 Number of courses
|
0 Number of courses
|
|
Number of HDMTX Courses With Delayed Early MTX Elimination (Definition E).
Undelayed early MTX elimination in Course SOC 1
|
4 Number of courses
|
4 Number of courses
|
|
Number of HDMTX Courses With Delayed Early MTX Elimination (Definition E).
Delayed early MTX elimination in Course SOC 2
|
0 Number of courses
|
0 Number of courses
|
|
Number of HDMTX Courses With Delayed Early MTX Elimination (Definition E).
Undelayed early MTX elimination in Course MOD 2
|
4 Number of courses
|
3 Number of courses
|
|
Number of HDMTX Courses With Delayed Early MTX Elimination (Definition E).
Undelayed early MTX elimination in Course SOC 2
|
4 Number of courses
|
4 Number of courses
|
|
Number of HDMTX Courses With Delayed Early MTX Elimination (Definition E).
Delayed early MTX elimination in Course MOD 1
|
0 Number of courses
|
0 Number of courses
|
|
Number of HDMTX Courses With Delayed Early MTX Elimination (Definition E).
Undelayed early MTX elimination in Course MOD 1
|
4 Number of courses
|
4 Number of courses
|
|
Number of HDMTX Courses With Delayed Early MTX Elimination (Definition E).
Delayed early MTX elimination in Course MOD 2
|
0 Number of courses
|
0 Number of courses
|
SECONDARY outcome
Timeframe: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/LPopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
Definition F: Delayed late MTX elimination (according to US label for Calcium Folinate) S-MTX level: \> 0.2 μmol/L at 72 hours AND \> 0.1 μmol/L at 96 hours after start of MTX administration.
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Number of HDMTX Courses With Delayed Late MTX Elimination (Definition F).
Delayed late MTX elimination in Course SOC 1
|
0 Number of courses
|
0 Number of courses
|
|
Number of HDMTX Courses With Delayed Late MTX Elimination (Definition F).
Undelayed late MTX elimination in Course SOC 2
|
3 Number of courses
|
1 Number of courses
|
|
Number of HDMTX Courses With Delayed Late MTX Elimination (Definition F).
Undelayed late MTX elimination in Course SOC 1
|
3 Number of courses
|
1 Number of courses
|
|
Number of HDMTX Courses With Delayed Late MTX Elimination (Definition F).
Delayed late MTX elimination in Course SOC 2
|
0 Number of courses
|
0 Number of courses
|
|
Number of HDMTX Courses With Delayed Late MTX Elimination (Definition F).
Delayed late MTX elimination in Course MOD 1
|
0 Number of courses
|
0 Number of courses
|
|
Number of HDMTX Courses With Delayed Late MTX Elimination (Definition F).
Undelayed late MTX elimination in Course MOD 1
|
2 Number of courses
|
1 Number of courses
|
|
Number of HDMTX Courses With Delayed Late MTX Elimination (Definition F).
Delayed late MTX elimination in Course MOD 2
|
0 Number of courses
|
1 Number of courses
|
|
Number of HDMTX Courses With Delayed Late MTX Elimination (Definition F).
Undelayed late MTX elimination in Course MOD 2
|
2 Number of courses
|
0 Number of courses
|
SECONDARY outcome
Timeframe: Time from start of MTX treatment until serum MTX level is ≤ 0.1 μmol/LPopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
The MTX-toxicity management instructions provided in the protocol are based on the Children's Oncology Group (COG) treatment management recommendations used in study protocol AOST0331, EURAMOS 1. The COG recommend changes in the hydration and the rescue frequency and/or dose to be done if pre-specified toxicities of different severity grades occur.
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A2 (24h) MOD 1
|
1 Number of MTX excretion toxicities
|
3 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A2 (24h) MOD 2
|
2 Number of MTX excretion toxicities
|
1 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade B (24h) SOC 1
|
1 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade B (24h) SOC 2
|
0 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade B (24h) MOD 1
|
1 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade B (24h) MOD 2
|
1 Number of MTX excretion toxicities
|
1 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
None (24h) SOC 1
|
1 Number of MTX excretion toxicities
|
2 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
None (24h) SOC 2
|
2 Number of MTX excretion toxicities
|
2 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A2 (48h) MOD 1
|
2 Number of MTX excretion toxicities
|
2 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A2 (48h) MOD 2
|
2 Number of MTX excretion toxicities
|
1 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade B (48h) SOC 1
|
1 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade B (48h) SOC 2
|
0 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
None (48h) SOC 1
|
2 Number of MTX excretion toxicities
|
2 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
None (48h) SOC 2
|
3 Number of MTX excretion toxicities
|
3 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
None (48h) MOD 2
|
2 Number of MTX excretion toxicities
|
1 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A2 (72h) SOC 1
|
1 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade B (72h) SOC 1
|
0 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade B (72h) SOC 2
|
0 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade B (72h) MOD 2
|
0 Number of MTX excretion toxicities
|
1 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
None (72h) SOC 1
|
1 Number of MTX excretion toxicities
|
4 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
None (72h) SOC 2
|
1 Number of MTX excretion toxicities
|
3 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A2 (24h) SOC 1
|
2 Number of MTX excretion toxicities
|
2 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A2 (24h) SOC 2
|
2 Number of MTX excretion toxicities
|
2 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
None (24h) MOD 1
|
2 Number of MTX excretion toxicities
|
1 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
None (24h) MOD 2
|
1 Number of MTX excretion toxicities
|
1 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A2 (48h) SOC 1
|
1 Number of MTX excretion toxicities
|
2 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A2 (48h) SOC 2
|
1 Number of MTX excretion toxicities
|
1 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade B (48h) MOD 1
|
0 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade B (48h) MOD 2
|
0 Number of MTX excretion toxicities
|
1 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
None (48h) MOD 1
|
2 Number of MTX excretion toxicities
|
2 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A1 (72h) SOC 1
|
2 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A1 (72h) SOC 2
|
2 Number of MTX excretion toxicities
|
1 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A1 (72h) MOD 1
|
1 Number of MTX excretion toxicities
|
1 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A1 (72h) MOD 2
|
2 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A2 (72h) SOC 2
|
1 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A2 (72h) MOD 1
|
1 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade A2 (72h) MOD 2
|
0 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
Grade B (72h) MOD 1
|
0 Number of MTX excretion toxicities
|
0 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
None (72h) MOD 1
|
2 Number of MTX excretion toxicities
|
3 Number of MTX excretion toxicities
|
|
Number of Grade A1, Grade A2, Grade B, Grade C, or Grade D Excretion Toxicities as Listed in the MTX-toxicity Management Instructions
None (72h) MOD 2
|
2 Number of MTX excretion toxicities
|
2 Number of MTX excretion toxicities
|
SECONDARY outcome
Timeframe: From the start of HDMTX administration through 8 days post dose for all 4 courses of HDMTX in totalPopulation: The All Patients Treated Set (APTS) included all patients receiving at least one bolus injection of Modufolin (MOD).
The severity of AEs have been done using NCI CTCAE v4.0. Total number of AEs per severity grade are presented for all AEs and for AEs related to MTX. For AEs related to MTX the number of AEs occurring per preferred term and severity grade are detailed.The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE; Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening, and Grade 5 Death related to AE.
Outcome measures
| Measure |
Cohort 1
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with Calcium Folinate (SOC) rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with Modufolin (MOD) rescue 15mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=4 Participants
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Any Grade (ALL AEs)
|
62 Number of AEs
|
49 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Grade 1 (AEs Related to MTX)
|
25 Number of AEs
|
20 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Grade 2 (AEs Related to MTX)
|
6 Number of AEs
|
12 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Grade 3 (AEs Related to MTX)
|
6 Number of AEs
|
5 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Grade 4 (AEs Related to MTX)
|
1 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Any Grade (AEs Related to MTX)
|
38 Number of AEs
|
38 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
ALAT increase (Related to MTX) Grade 1
|
2 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
ALAT increase (Related to MTX) Grade 2
|
1 Number of AEs
|
3 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
ALAT increase (Related to MTX) Grade 3
|
4 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Anemia (Related to MTX) Grade 1
|
3 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Anemia (Related to MTX) Grade 3
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Anemia (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
ASAT increased (Related to MTX) Any Grade
|
7 Number of AEs
|
2 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Cheilitis (Related to MTX) Grade 1
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Convulsion (Related to MTX) Grade 2
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Convulsion (Related to MTX) Grade 3
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Convulsion (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Convulsion (Related to MTX) Any Grade
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Diarrhoea (Related to MTX) Grade 1
|
2 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Diarrhoea (Related to MTX) Grade 2
|
1 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Diarrhoea (Related to MTX) Grade 3
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Diarrhoea (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Diarrhoea (Related to MTX) Any Grade
|
3 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Drug clearance decreased (Related to MTX) Grade 1
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Drug clearance decreased (Related to MTX) Grade 2
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Drug clearance decreased (Related to MTX) Grade 3
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Drug clearance decreased (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Drug clearance decreased (Related to MTX) AnyGrade
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Febrile neutropenia (Related to MTX) Grade 1
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Febrile neutropenia (Related to MTX) Grade 2
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Febrile neutropenia (Related to MTX) Grade 3
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Febrile neutropenia (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Febrile neutropenia (Related to MTX) Any Grade
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Headache (Related to MTX) Grade 1
|
1 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Headache (Related to MTX) Grade 2
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Headache (Related to MTX) Grade 3
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Headache (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Headache (Related to MTX) Any Grade
|
1 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Nausea (Related to MTX) Grade 1
|
2 Number of AEs
|
4 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Nausea (Related to MTX) Grade 2
|
0 Number of AEs
|
2 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Nausea (Related to MTX) Grade 3
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Nausea (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Nausea (Related to MTX) Any Grade
|
2 Number of AEs
|
6 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Nephropathy (Related to MTX) Grade 1
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Nephropathy (Related to MTX) Grade 21
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Nephropathy (Related to MTX) Grade 3
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Nephropathy (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Nephropathy (Related to MTX) Any Grade
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Neutropenia (Related to MTX) Grade 1
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Neutropenia (Related to MTX) Grade 2
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Neutropenia (Related to MTX) Grade 3
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Neutropenia (Related to MTX) Grade 4
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Neutropenia (Related to MTX) Any Grade
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Neutrophil count decrease (Related to MTX) Grade 1
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Pyrexia (Related to MTX) Grade 1
|
1 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Pyrexia (Related to MTX) Grade 2
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Pyrexia (Related to MTX) Grade 3
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Pyrexia (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Pyrexia (Related to MTX) Any Grade
|
1 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Stomatitis (Related to MTX) Grade 1
|
0 Number of AEs
|
3 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Stomatitis (Related to MTX) Grade 2
|
0 Number of AEs
|
2 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Stomatitis (Related to MTX) Grade 3
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Stomatitis (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Stomatitis (Related to MTX) Any Grade
|
0 Number of AEs
|
6 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Vomiting (Related to MTX) Grade 1
|
9 Number of AEs
|
8 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Vomiting (Related to MTX) Grade 2
|
0 Number of AEs
|
2 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Vomiting (Related to MTX) Grade 3
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Vomiting (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Vomiting (Related to MTX) Any Grade
|
9 Number of AEs
|
10 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
WBC count decreased (Related to MTX) Grade 1
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
WBC count decreased (Related to MTX) Grade 2
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
WBC count decreased (Related to MTX) Grade 3
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
WBC count decreased (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
WBC count decreased (Related to MTX) Any Grade
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Grade 1 (ALL AEs)
|
40 Number of AEs
|
27 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Grade 2 (ALL AEs)
|
8 Number of AEs
|
15 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Grade 3 (ALL AEs)
|
11 Number of AEs
|
6 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Grade 4 (ALL AEs)
|
3 Number of AEs
|
9 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
ALAT increase (Related to MTX) Grade 4
|
1 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
ALAT increase (Related to MTX) Any Grade
|
8 Number of AEs
|
3 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Anemia (Related to MTX) Grade 2
|
4 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Anemia (Related to MTX) Any Grade
|
7 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
ASAT increased (Related to MTX) Grade 1
|
5 Number of AEs
|
2 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
ASAT increased (Related to MTX) Grade 2
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
ASAT increased (Related to MTX) Grade 3
|
2 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
ASAT increased (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Cheilitis (Related to MTX) Grade 2
|
0 Number of AEs
|
2 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Cheilitis (Related to MTX) Grade 3
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Cheilitis (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Cheilitis (Related to MTX) Any Grade
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Convulsion (Related to MTX) Grade 1
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Neutrophil count decrease (Related to MTX) Grade 2
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Neutrophil count decrease (Related to MTX) Grade 3
|
0 Number of AEs
|
1 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Neutrophil count decrease (Related to MTX) Grade 4
|
0 Number of AEs
|
0 Number of AEs
|
|
Characterization (Number/Severity) of All Reported AEs During the ENTIRE STUDY PERIOD.
Neutrophil count decrease (Related to MTX)AnyGrade
|
0 Number of AEs
|
1 Number of AEs
|
Adverse Events
Cohort 1
Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths
Cohort 2
Serious events: 3 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1
n=8 participants at risk
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 15mg/m2)
SOC was administered as rescue in the 2 first HDMTX courses and MOD in the 2 following courses.
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=10 participants at risk
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
SOC was administered as rescue in the 2 first HDMTX courses and MOD in the 2 following courses.
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Investigations
Platelet count decreased
|
12.5%
1/8 • Number of events 3 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
0.00%
0/10 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
12.5%
1/8 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Nervous system disorders
Convulsion
|
0.00%
0/8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
General disorders
Mucosal inflammation
|
0.00%
0/8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Infections and infestations
Candida sepsis
|
12.5%
1/8 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
0.00%
0/10 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Infections and infestations
Neutropenic sepsis
|
0.00%
0/8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
Other adverse events
| Measure |
Cohort 1
n=8 participants at risk
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 15mg/m2)
SOC was administered as rescue in the 2 first HDMTX courses and MOD in the 2 following courses.
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
Cohort 2
n=10 participants at risk
1 MAP cycle (incl. 2 HDMTX courses with SOC rescue 15mg/m2)
1 MAP cycle (incl. 2 HDMTX courses with MOD rescue 7.5mg/m2)
SOC was administered as rescue in the 2 first HDMTX courses and MOD in the 2 following courses.
Treatment according to the MAP schedule applied. SOC or MOD commenced 24 h after administration of HDMTX and then every 6 h until the serum-MTX levels were ≤ 0.1 µmol/L, in accordance with COG management recommendations.
|
|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
25.0%
2/8 • Number of events 8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 3 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Investigations
Aspartate aminotransferase increased
|
25.0%
2/8 • Number of events 7 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 2 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Investigations
Drug clearance decreased
|
0.00%
0/8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Investigations
Platelet count decreased
|
12.5%
1/8 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
0.00%
0/10 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Investigations
White blood cell count decreased
|
12.5%
1/8 • Number of events 2 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
25.0%
1/4 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Cardiac disorders
Left ventricular dysfunction
|
12.5%
1/8 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
0.00%
0/10 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
12.5%
1/8 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
0.00%
0/10 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Blood and lymphatic system disorders
Anaemia
|
12.5%
1/8 • Number of events 9 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
0.00%
0/10 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Nervous system disorders
Headache
|
25.0%
2/8 • Number of events 2 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
General disorders
Localised oedema
|
0.00%
0/8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
General disorders
Mucosal inflammation
|
0.00%
0/8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
20.0%
2/10 • Number of events 3 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
General disorders
Pyrexia
|
25.0%
2/8 • Number of events 2 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
0.00%
0/10 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
2/8 • Number of events 4 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
0.00%
0/10 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Gastrointestinal disorders
Nausea
|
25.0%
2/8 • Number of events 2 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
30.0%
3/10 • Number of events 7 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Gastrointestinal disorders
Stomatitis
|
25.0%
2/8 • Number of events 2 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
20.0%
2/10 • Number of events 4 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
4/8 • Number of events 14 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
40.0%
4/10 • Number of events 13 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Renal and urinary disorders
Nephropathy
|
0.00%
0/8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
12.5%
1/8 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
0.00%
0/10 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Infections and infestations
Bacterial disease carrier
|
12.5%
1/8 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
0.00%
0/10 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Infections and infestations
Cheilitis
|
0.00%
0/8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 3 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Infections and infestations
Conjunctivitis
|
0.00%
0/8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/8 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
10.0%
1/10 • Number of events 1 • 3 years, 1 month
The time-frame for reporting adverse events: From the start of HDMTX administration through 8 days post dose for each course of HDMTX.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee At least 30 d prior to submission the PI shall provide the Sponsor with results communication for review. The Sponsor shall notify the PI in writing about the review outcome within 30 d from receipt. No public release shall be made unless the Sponsor has consented in writing. The Sponsor may notify the PI that the material shall be withhold from submission for 90 days more to allow filing of applications to secure IPR or to take such measures to establish and preserve its proprietary rights.
- Publication restrictions are in place
Restriction type: OTHER