Trial Outcomes & Findings for UARK 89-001 Phase II Study of Intensive "TOTAL THERAPY" For Untreated or Minimally Treated Patients With Multiple Myeloma (NCT NCT00580372)
NCT ID: NCT00580372
Last Updated: 2016-09-20
Results Overview
Relapse is defined by the unequivocal objective evidence of recurrent disease such as: myeloma-related cytogenetic abnormalities; bone marrow plasmacytosis \>10% or \>5% light chain restricted, non-diploid, plasma cells on clg/DNA; new skeletal or MRI lesions; hypercalcemia not explained by any other cause; or reappearance of M-protein in blood or urine not related to immune recovery, recent infection, and present for \>2 months.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
231 participants
Primary outcome timeframe
5 years
Results posted on
2016-09-20
Participant Flow
Participant milestones
| Measure |
Study Treatment
Protocol therapy consists of a remission induction phase with mutually non-cross resistant combinations of vincristine, adriamycin, dexamethasone (VAD), high-dose cyclophosphamide with stem cell procurement and etoposide, dexamethasone, cytarabine, cisplatin (EDAP) followed by two courses of melphalan-based high-dose therapy supported by autologous stem cell transplants 4-6 months apart. Maintenance with interferon alpha will be administered until disease progression.
VAD: 3 Cycles (3rd cycle optional):
Vincristine 0.5 mg/d d 1 - 4 CI Adriamycin 10 mg/m2/d d 1 - 4 CI Dexamethasone 40 mg/d d 1-4, 9-12, 17-20
High-Dose cyclophosphamide: Approximately 5-6 weeks after VAD 2 or 3:
Cytoxan 1.2g/m2/d d 1 - 5 Mesna 3.6 g/m2 d 1
Hemopoietic stem cell procurement: Collection target = 10 x 10\^6 cells/kg
EDAP: Approximately 5-6 weeks after high-dose cyclophosphamide
|
|---|---|
|
Overall Study
STARTED
|
231
|
|
Overall Study
COMPLETED
|
231
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
UARK 89-001 Phase II Study of Intensive "TOTAL THERAPY" For Untreated or Minimally Treated Patients With Multiple Myeloma
Baseline characteristics by cohort
| Measure |
Study Treatment
n=231 Participants
Protocol therapy consists of a remission induction phase with mutually non-cross resistant combinations of vincristine, adriamycin, dexamethasone (VAD), high-dose cyclophosphamide with stem cell procurement and etoposide, dexamethasone, cytarabine, cisplatin (EDAP) followed by two courses of melphalan-based high-dose therapy supported by autologous stem cell transplants 4-6 months apart. Maintenance with interferon alpha will be administered until disease progression.
VAD: 3 Cycles (3rd cycle optional):
Vincristine 0.5 mg/d d 1 - 4 CI Adriamycin 10 mg/m2/d d 1 - 4 CI Dexamethasone 40 mg/d d 1-4, 9-12, 17-20
High-Dose cyclophosphamide: Approximately 5-6 weeks after VAD 2 or 3:
Cytoxan 1.2g/m2/d d 1 - 5 Mesna 3.6 g/m2 d 1
Hemopoietic stem cell procurement: Collection target = 10 x 10\^6 cells/kg
EDAP: Approximately 5-6 weeks after high-dose cyclophosphamide
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
211 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
20 Participants
n=93 Participants
|
|
Age, Continuous
|
51.6 years
n=93 Participants
|
|
Sex: Female, Male
Female
|
91 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
140 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
231 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 5 yearsRelapse is defined by the unequivocal objective evidence of recurrent disease such as: myeloma-related cytogenetic abnormalities; bone marrow plasmacytosis \>10% or \>5% light chain restricted, non-diploid, plasma cells on clg/DNA; new skeletal or MRI lesions; hypercalcemia not explained by any other cause; or reappearance of M-protein in blood or urine not related to immune recovery, recent infection, and present for \>2 months.
Outcome measures
| Measure |
Study Treatment
n=231 Participants
Protocol therapy consists of a remission induction phase with mutually non-cross resistant combinations of vincristine, adriamycin, dexamethasone (VAD), high-dose cyclophosphamide with stem cell procurement and etoposide, dexamethasone, cytarabine, cisplatin (EDAP) followed by two courses of melphalan-based high-dose therapy supported by autologous stem cell transplants 4-6 months apart. Maintenance with interferon alpha will be administered until disease progression.
VAD: 3 Cycles (3rd cycle optional):
Vincristine 0.5 mg/d d 1 - 4 CI Adriamycin 10 mg/m2/d d 1 - 4 CI Dexamethasone 40 mg/d d 1-4, 9-12, 17-20
High-Dose cyclophosphamide: Approximately 5-6 weeks after VAD 2 or 3:
Cytoxan 1.2g/m2/d d 1 - 5 Mesna 3.6 g/m2 d 1
Hemopoietic stem cell procurement: Collection target = 10 x 10\^6 cells/kg
EDAP: Approximately 5-6 weeks after high-dose cyclophosphamide
|
|---|---|
|
Percentage of Participants That Are Relapse-free 5 Years After Initial Therapy
|
28 percentage of participants
|
Adverse Events
Study Treatment
Serious events: 231 serious events
Other events: 231 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Study Treatment
n=231 participants at risk
Protocol therapy consists of a remission induction phase with mutually non-cross resistant combinations of vincristine, adriamycin, dexamethasone (VAD), high-dose cyclophosphamide with stem cell procurement and etoposide, dexamethasone, cytarabine, cisplatin (EDAP) followed by two courses of melphalan-based high-dose therapy supported by autologous stem cell transplants 4-6 months apart. Maintenance with interferon alpha will be administered until disease progression.
VAD: 3 Cycles (3rd cycle optional):
Vincristine 0.5 mg/d d 1 - 4 CI Adriamycin 10 mg/m2/d d 1 - 4 CI Dexamethasone 40 mg/d d 1-4, 9-12, 17-20
High-Dose cyclophosphamide: Approximately 5-6 weeks after VAD 2 or 3:
Cytoxan 1.2g/m2/d d 1 - 5 Mesna 3.6 g/m2 d 1
Hemopoietic stem cell procurement: Collection target = 10 x 10\^6 cells/kg
EDAP: Approximately 5-6 weeks after high-dose cyclophosphamide
|
|---|---|
|
Blood and lymphatic system disorders
Blood/bone marrow Grade 4
|
67.1%
155/231
|
|
Blood and lymphatic system disorders
Anemia Grade 4
|
4.3%
10/231
|
|
Blood and lymphatic system disorders
Neutropeni Grade 4
|
58.9%
136/231
|
|
Blood and lymphatic system disorders
WBC Grade 4
|
64.9%
150/231
|
|
Blood and lymphatic system disorders
Thrombocyt Grade 4
|
16.0%
37/231
|
|
Endocrine disorders
Hepatobiliary/pancreas grade 3
|
17.7%
41/231
|
|
Endocrine disorders
Hepatobiliary/pancreas grade 4
|
0.43%
1/231
|
|
Endocrine disorders
Alkaline grade 3
|
2.2%
5/231
|
|
Endocrine disorders
Bilirubin grade 3
|
5.2%
12/231
|
|
Endocrine disorders
Bilirubin grade 4
|
0.43%
1/231
|
|
Endocrine disorders
Hypoalbumi grade 3
|
11.3%
26/231
|
|
Endocrine disorders
SGOT (AST) grade 3
|
1.7%
4/231
|
|
Endocrine disorders
SGPT (ALT) grade 3
|
3.5%
8/231
|
|
Metabolism and nutrition disorders
Metabolic/laboratory grade 3
|
38.5%
89/231
|
|
Metabolism and nutrition disorders
Metabolic/laboratory grade 4
|
12.1%
28/231
|
|
Metabolism and nutrition disorders
Bicarbonat grade 3
|
0.87%
2/231
|
|
Metabolism and nutrition disorders
Hypercalce grade 3
|
1.3%
3/231
|
|
Metabolism and nutrition disorders
Hypercalce grade 4
|
0.87%
2/231
|
|
Metabolism and nutrition disorders
Hyperglyce grade 3
|
6.5%
15/231
|
|
Metabolism and nutrition disorders
Hyperglyce grade 4
|
2.6%
6/231
|
|
Metabolism and nutrition disorders
Hyperkalem grade 3
|
3.0%
7/231
|
|
Metabolism and nutrition disorders
Hyperkalem grade 4
|
1.3%
3/231
|
|
Metabolism and nutrition disorders
Hypermagne grade 3
|
0.87%
2/231
|
|
Metabolism and nutrition disorders
Hypematre grade 3
|
0.87%
2/231
|
|
Metabolism and nutrition disorders
Hypematre grade 4
|
0.87%
2/231
|
|
Metabolism and nutrition disorders
Hypocalcem grade 3
|
4.8%
11/231
|
|
Metabolism and nutrition disorders
Hypocalcem grade 4
|
4.3%
10/231
|
|
Metabolism and nutrition disorders
Hypokalemi grade 3
|
16.9%
39/231
|
|
Metabolism and nutrition disorders
Hypokalemi grade 4
|
1.3%
3/231
|
|
Metabolism and nutrition disorders
Hypomagnes grade 3
|
1.7%
4/231
|
|
Metabolism and nutrition disorders
Hypomagnes grade 4
|
0.43%
1/231
|
|
Metabolism and nutrition disorders
Hyponatrem grade 3
|
14.7%
34/231
|
|
Metabolism and nutrition disorders
Hyponatrem grade 4
|
0.87%
2/231
|
|
Metabolism and nutrition disorders
Hypophosph grade 3
|
35.9%
83/231
|
|
Metabolism and nutrition disorders
Hypophosph grade 4
|
0.43%
1/231
|
|
Renal and urinary disorders
Renal/Genitourinary grade 3
|
6.1%
14/231
|
|
Renal and urinary disorders
Renal/Genitourinary grade 4
|
3.9%
9/231
|
|
Renal and urinary disorders
Creatinine grade 3
|
6.1%
14/231
|
|
Renal and urinary disorders
Creatinine grade 4
|
3.9%
9/231
|
Other adverse events
| Measure |
Study Treatment
n=231 participants at risk
Protocol therapy consists of a remission induction phase with mutually non-cross resistant combinations of vincristine, adriamycin, dexamethasone (VAD), high-dose cyclophosphamide with stem cell procurement and etoposide, dexamethasone, cytarabine, cisplatin (EDAP) followed by two courses of melphalan-based high-dose therapy supported by autologous stem cell transplants 4-6 months apart. Maintenance with interferon alpha will be administered until disease progression.
VAD: 3 Cycles (3rd cycle optional):
Vincristine 0.5 mg/d d 1 - 4 CI Adriamycin 10 mg/m2/d d 1 - 4 CI Dexamethasone 40 mg/d d 1-4, 9-12, 17-20
High-Dose cyclophosphamide: Approximately 5-6 weeks after VAD 2 or 3:
Cytoxan 1.2g/m2/d d 1 - 5 Mesna 3.6 g/m2 d 1
Hemopoietic stem cell procurement: Collection target = 10 x 10\^6 cells/kg
EDAP: Approximately 5-6 weeks after high-dose cyclophosphamide
|
|---|---|
|
Blood and lymphatic system disorders
Anemia grade 2
|
22.5%
52/231
|
|
Blood and lymphatic system disorders
Thrombocyt grade 2
|
14.7%
34/231
|
|
Endocrine disorders
Hepatobiliary/ pancreas grade 1
|
13.0%
30/231
|
|
Endocrine disorders
Hepatobiliary/pancreas grade 2
|
59.7%
138/231
|
|
Endocrine disorders
Alkaline grade 1
|
30.3%
70/231
|
|
Endocrine disorders
Alkaline grade 2
|
6.1%
14/231
|
|
Endocrine disorders
Bilirubin grade 1
|
16.5%
38/231
|
|
Endocrine disorders
Bilirubin grade 2
|
7.4%
17/231
|
|
Endocrine disorders
Hypoalbumi grade 1
|
14.7%
34/231
|
|
Endocrine disorders
Hypoalbumi grade 2
|
64.9%
150/231
|
|
Endocrine disorders
SGOT (AST) grade 1
|
33.8%
78/231
|
|
Endocrine disorders
SGOT (AST) grade 2
|
5.6%
13/231
|
|
Endocrine disorders
SGPT (ALT) grade 1
|
32.9%
76/231
|
|
Endocrine disorders
SGPT (ALT) grade 2
|
8.7%
20/231
|
|
Metabolism and nutrition disorders
Metabolic/laboratory grade 2
|
16.5%
38/231
|
|
Metabolism and nutrition disorders
Bicarbonat grade 1
|
42.0%
97/231
|
|
Metabolism and nutrition disorders
Hypercalce grade 1
|
7.4%
17/231
|
|
Metabolism and nutrition disorders
Hyperglyce grade 1
|
22.9%
53/231
|
|
Metabolism and nutrition disorders
Hyperglyce grade 2
|
23.8%
55/231
|
|
Metabolism and nutrition disorders
Hyperkalem grade 1
|
18.6%
43/231
|
|
Metabolism and nutrition disorders
Hyperkalem grade 2
|
12.6%
29/231
|
|
Metabolism and nutrition disorders
Hypemagne grade 1
|
11.7%
27/231
|
|
Metabolism and nutrition disorders
Hypematre grade 1
|
27.3%
63/231
|
|
Metabolism and nutrition disorders
Hypocalcem grade 1
|
30.7%
71/231
|
|
Metabolism and nutrition disorders
Hypocalcem grade 2
|
24.7%
57/231
|
|
Metabolism and nutrition disorders
Hypokalemi grade 1
|
45.5%
105/231
|
|
Metabolism and nutrition disorders
Hypomagnes grade 1
|
50.2%
116/231
|
|
Metabolism and nutrition disorders
Hypomagnes grade 2
|
10.8%
25/231
|
|
Metabolism and nutrition disorders
Hyponatrem grade 1
|
42.0%
97/231
|
|
Metabolism and nutrition disorders
Hypophosph grade 2
|
27.3%
63/231
|
|
Renal and urinary disorders
Renal/genitourinary grade 1
|
27.7%
64/231
|
|
Renal and urinary disorders
Renal/genitourinary grade 2
|
15.2%
35/231
|
|
Renal and urinary disorders
Creatinine grade 1
|
27.7%
64/231
|
|
Renal and urinary disorders
Creatinine grade 2
|
15.2%
35/231
|
Additional Information
Dr. Bart Barlogie
University of Arkansas for Medical Science
Phone: 501-526-2873
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place