Trial Outcomes & Findings for CLAG Gleevec in Relapsed or Refractory Acute Myeloid Leukemia (AML) (NCT NCT00955916)
NCT ID: NCT00955916
Last Updated: 2014-06-27
Results Overview
Overall Response Rate: Morphologic Complete Remission (CR) + Morphologic Complete Remission with incomplete blood count recovery (CRi) for evaluable participants. CR - Bone Marrow: \< 5% blasts without Auer rods with at least 20% cellularity with maturation of all cell lines, No presence of unique phenotype by flow cytometry identical to what was found in the pretreatment specimen, No persistent dysplasia; Peripheral: normal blood counts, absolute neutrophil count (ANC) \> 1.0 k/μl and platelets \> 100 k/μl ANC \> 1.0 k/μl and platelets \> 100 k/μl (Peripheral blood counts documenting recovery can be utilized within 4 weeks of the bone marrow); No evidence of extramedullary leukemia. CRi - All CR criteria are met except for residual Neutropenia \<1.0 x 10\^9/L platelets \< 100 k/μl.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
38 participants
Primary outcome timeframe
8 weeks per participant
Results posted on
2014-06-27
Participant Flow
Between August 2009 and April 2011, participants were enrolled at Moffitt Cancer Center.
Participant milestones
| Measure |
CLAG Regimen With Gleevec®
Combined chemotherapy treatment (CLAG regimen) with Gleevec® (imatinib mesylate).
Gleevec®: Imatinib mesylate 400 mg orally twice daily was administered on day 2 to day 15. Re-induction was allowed if participant had partial response (PR).
CLAG Regimen: The CLAG regimen consisted of: Cladribine, 5 mg/m\^2 administered via 2 hour IV daily for 5 consecutive days starting on day 2; Cytarabine, 2 mg/m\^2 administered through a 4 hour IV starting 2 hours after the ignition of Cladribine for 5 days starting on day 2; granulocyte colony-stimulating factor (G-CSF): 300 mcg subcutaneous (SC) for 6 days starting 12-24 hours (Day 1) before the first dose of Cladribine.
|
|---|---|
|
Overall Study
STARTED
|
38
|
|
Overall Study
COMPLETED
|
38
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
CLAG Gleevec in Relapsed or Refractory Acute Myeloid Leukemia (AML)
Baseline characteristics by cohort
| Measure |
CLAG Regimen With Gleevec®
n=38 Participants
Combined chemotherapy treatment (CLAG regimen) with Gleevec® (imatinib mesylate).
Gleevec®: Imatinib mesylate 400 mg orally twice daily was administered on day 2 to day 15. Re-induction was allowed if participant had partial response (PR).
CLAG Regimen: The CLAG regimen consisted of: Cladribine, 5 mg/m\^2 administered via 2 hour IV daily for 5 consecutive days starting on day 2; Cytarabine, 2 mg/m\^2 administered through a 4 hour IV starting 2 hours after the ignition of Cladribine for 5 days starting on day 2; granulocyte colony-stimulating factor (G-CSF): 300 mcg subcutaneous (SC) for 6 days starting 12-24 hours (Day 1) before the first dose of Cladribine.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
23 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
15 Participants
n=5 Participants
|
|
Age, Continuous
|
62 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
38 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 weeks per participantPopulation: All participants
Overall Response Rate: Morphologic Complete Remission (CR) + Morphologic Complete Remission with incomplete blood count recovery (CRi) for evaluable participants. CR - Bone Marrow: \< 5% blasts without Auer rods with at least 20% cellularity with maturation of all cell lines, No presence of unique phenotype by flow cytometry identical to what was found in the pretreatment specimen, No persistent dysplasia; Peripheral: normal blood counts, absolute neutrophil count (ANC) \> 1.0 k/μl and platelets \> 100 k/μl ANC \> 1.0 k/μl and platelets \> 100 k/μl (Peripheral blood counts documenting recovery can be utilized within 4 weeks of the bone marrow); No evidence of extramedullary leukemia. CRi - All CR criteria are met except for residual Neutropenia \<1.0 x 10\^9/L platelets \< 100 k/μl.
Outcome measures
| Measure |
CLAG Regimen With Gleevec®
n=38 Participants
Combined chemotherapy treatment (CLAG regimen) with Gleevec® (imatinib mesylate).
Gleevec®: Imatinib mesylate 400 mg orally twice daily was administered on day 2 to day 15. Re-induction was allowed if participant had partial response (PR).
CLAG Regimen: The CLAG regimen consisted of: Cladribine, 5 mg/m\^2 administered via 2 hour IV daily for 5 consecutive days starting on day 2; Cytarabine, 2 mg/m\^2 administered through a 4 hour IV starting 2 hours after the ignition of Cladribine for 5 days starting on day 2; granulocyte colony-stimulating factor (G-CSF): 300 mcg subcutaneous (SC) for 6 days starting 12-24 hours (Day 1) before the first dose of Cladribine.
|
|---|---|
|
Overall Response Rate (ORR)
|
37 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 3 yearsPopulation: All participants
Progression Free Survival is defined as the duration of time from start of treatment to time of progression. Leukemia related failure (progressive disease): Failure to induce bone marrow hypoplasia after 2 cycles or regrowth of leukemic blasts ≥ 20%.
Outcome measures
| Measure |
CLAG Regimen With Gleevec®
n=38 Participants
Combined chemotherapy treatment (CLAG regimen) with Gleevec® (imatinib mesylate).
Gleevec®: Imatinib mesylate 400 mg orally twice daily was administered on day 2 to day 15. Re-induction was allowed if participant had partial response (PR).
CLAG Regimen: The CLAG regimen consisted of: Cladribine, 5 mg/m\^2 administered via 2 hour IV daily for 5 consecutive days starting on day 2; Cytarabine, 2 mg/m\^2 administered through a 4 hour IV starting 2 hours after the ignition of Cladribine for 5 days starting on day 2; granulocyte colony-stimulating factor (G-CSF): 300 mcg subcutaneous (SC) for 6 days starting 12-24 hours (Day 1) before the first dose of Cladribine.
|
|---|---|
|
Median Progression Free Survival (PFS)
|
11.1 months
Interval 4.8 to 13.4
|
SECONDARY outcome
Timeframe: Up to 3 yearsPopulation: All participants
Overall Survival is defined as the time from randomization until death from any cause.
Outcome measures
| Measure |
CLAG Regimen With Gleevec®
n=38 Participants
Combined chemotherapy treatment (CLAG regimen) with Gleevec® (imatinib mesylate).
Gleevec®: Imatinib mesylate 400 mg orally twice daily was administered on day 2 to day 15. Re-induction was allowed if participant had partial response (PR).
CLAG Regimen: The CLAG regimen consisted of: Cladribine, 5 mg/m\^2 administered via 2 hour IV daily for 5 consecutive days starting on day 2; Cytarabine, 2 mg/m\^2 administered through a 4 hour IV starting 2 hours after the ignition of Cladribine for 5 days starting on day 2; granulocyte colony-stimulating factor (G-CSF): 300 mcg subcutaneous (SC) for 6 days starting 12-24 hours (Day 1) before the first dose of Cladribine.
|
|---|---|
|
Median Overall Survival (OS)
|
4.9 months
Interval 1.6 to 11.7
|
Adverse Events
CLAG Regimen With Gleevec®
Serious events: 8 serious events
Other events: 38 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
CLAG Regimen With Gleevec®
n=38 participants at risk
Combined chemotherapy treatment (CLAG regimen) with Gleevec® (imatinib mesylate).
Gleevec®: Imatinib mesylate 400 mg orally twice daily was administered on day 2 to day 15. Re-induction was allowed if participant had partial response (PR).
CLAG Regimen: The CLAG regimen consisted of: Cladribine, 5 mg/m\^2 administered via 2 hour IV daily for 5 consecutive days starting on day 2; Cytarabine, 2 mg/m\^2 administered through a 4 hour IV starting 2 hours after the ignition of Cladribine for 5 days starting on day 2; granulocyte colony-stimulating factor (G-CSF): 300 mcg subcutaneous (SC) for 6 days starting 12-24 hours (Day 1) before the first dose of Cladribine.
|
|---|---|
|
General disorders
Death not associated with CTCAE term - Disease progression NOS
|
2.6%
1/38 • Number of events 1 • 1 year, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory - Lung
|
2.6%
1/38 • Number of events 1 • 1 year, 10 months
|
|
Hepatobiliary disorders
Liver dysfunction/failure (clinical)
|
2.6%
1/38 • Number of events 1 • 1 year, 10 months
|
|
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Blood
|
2.6%
1/38 • Number of events 1 • 1 year, 10 months
|
|
Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)
|
2.6%
1/38 • Number of events 1 • 1 year, 10 months
|
|
General disorders
Pain - Abdomen NOS
|
2.6%
1/38 • Number of events 1 • 1 year, 10 months
|
|
General disorders
Pain - Cardiac/heart
|
2.6%
1/38 • Number of events 1 • 1 year, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome (ARDS)
|
2.6%
1/38 • Number of events 1 • 1 year, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
2.6%
1/38 • Number of events 1 • 1 year, 10 months
|
|
Vascular disorders
Thrombosis/embolism (vascular access-related)
|
2.6%
1/38 • Number of events 1 • 1 year, 10 months
|
Other adverse events
| Measure |
CLAG Regimen With Gleevec®
n=38 participants at risk
Combined chemotherapy treatment (CLAG regimen) with Gleevec® (imatinib mesylate).
Gleevec®: Imatinib mesylate 400 mg orally twice daily was administered on day 2 to day 15. Re-induction was allowed if participant had partial response (PR).
CLAG Regimen: The CLAG regimen consisted of: Cladribine, 5 mg/m\^2 administered via 2 hour IV daily for 5 consecutive days starting on day 2; Cytarabine, 2 mg/m\^2 administered through a 4 hour IV starting 2 hours after the ignition of Cladribine for 5 days starting on day 2; granulocyte colony-stimulating factor (G-CSF): 300 mcg subcutaneous (SC) for 6 days starting 12-24 hours (Day 1) before the first dose of Cladribine.
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
76.3%
29/38 • Number of events 30 • 1 year, 10 months
|
|
Gastrointestinal disorders
Nausea
|
73.7%
28/38 • Number of events 29 • 1 year, 10 months
|
|
Gastrointestinal disorders
Vomiting
|
52.6%
20/38 • Number of events 22 • 1 year, 10 months
|
|
Gastrointestinal disorders
Anorexia
|
31.6%
12/38 • Number of events 12 • 1 year, 10 months
|
|
Gastrointestinal disorders
Constipation
|
23.7%
9/38 • Number of events 10 • 1 year, 10 months
|
|
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam) - Oral cavity
|
21.1%
8/38 • Number of events 8 • 1 year, 10 months
|
|
Gastrointestinal disorders
Taste alteration (dysgeusia)
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
Gastrointestinal disorders
Dehydration
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Gastrointestinal disorders
Gastrointestinal - Other
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Infections and infestations
Febrile neutropenia
|
57.9%
22/38 • Number of events 31 • 1 year, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Infection with Grade 3 or 4 neutrophils - Lung (pneumonia)
|
42.1%
16/38 • Number of events 18 • 1 year, 10 months
|
|
Infections and infestations
Infection with Grade 3 or 4 neutrophils - Blood
|
31.6%
12/38 • Number of events 12 • 1 year, 10 months
|
|
Infections and infestations
Infection - Other
|
26.3%
10/38 • Number of events 11 • 1 year, 10 months
|
|
Infections and infestations
Infection with Grade 3 or 4 neutrophils - Small bowel NOS
|
15.8%
6/38 • Number of events 6 • 1 year, 10 months
|
|
Infections and infestations
Infection with Grade 3 or 4 neutrophils - Urinary tract NOS
|
13.2%
5/38 • Number of events 5 • 1 year, 10 months
|
|
Infections and infestations
Infection with Grade 3 or 4 neutrophils - Colon
|
10.5%
4/38 • Number of events 4 • 1 year, 10 months
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Lung (pneumonia)
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Blood
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Mucosa
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Urinary tract NOS
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Skin and subcutaneous tissue disorders
Infection with Grade 3 or 4 neutrophils - Skin (cellulitis
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
Infections and infestations
Infection with unknown AND - Lung (pneumonia)
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Blood and lymphatic system disorders
Edema: limb
|
84.2%
32/38 • Number of events 35 • 1 year, 10 months
|
|
Blood and lymphatic system disorders
Lymphatics - Other
|
21.1%
8/38 • Number of events 8 • 1 year, 10 months
|
|
Blood and lymphatic system disorders
Edema: head and neck
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)
|
39.5%
15/38 • Number of events 17 • 1 year, 10 months
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
28.9%
11/38 • Number of events 11 • 1 year, 10 months
|
|
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)
|
21.1%
8/38 • Number of events 8 • 1 year, 10 months
|
|
Metabolism and nutrition disorders
Magnesium, serum-low (hypomagnesemia)
|
21.1%
8/38 • Number of events 8 • 1 year, 10 months
|
|
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)
|
15.8%
6/38 • Number of events 6 • 1 year, 10 months
|
|
Metabolism and nutrition disorders
AST, SGOT (serum glutamic oxaloacetic transaminase)
|
13.2%
5/38 • Number of events 5 • 1 year, 10 months
|
|
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory)
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
General disorders
Rigors/chills
|
44.7%
17/38 • Number of events 24 • 1 year, 10 months
|
|
General disorders
Insomnia
|
18.4%
7/38 • Number of events 7 • 1 year, 10 months
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
13.2%
5/38 • Number of events 5 • 1 year, 10 months
|
|
General disorders
Constitutional Symptoms - Other
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
General disorders
Fever (in the absence of neutropenia)
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
General disorders
Sweating (diaphoresis)
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
General disorders
Weight gain
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
General disorders
Pain - Head/headache
|
21.1%
8/38 • Number of events 8 • 1 year, 10 months
|
|
General disorders
Pain - Back
|
13.2%
5/38 • Number of events 5 • 1 year, 10 months
|
|
General disorders
Pain - Abdomen NOS
|
10.5%
4/38 • Number of events 4 • 1 year, 10 months
|
|
General disorders
Pain - Extremity-limb
|
10.5%
4/38 • Number of events 4 • 1 year, 10 months
|
|
General disorders
Pain - Joint
|
10.5%
4/38 • Number of events 5 • 1 year, 10 months
|
|
General disorders
Pain-Cardiac/heart
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
General disorders
Pain - Chest/thorax NOS
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
General disorders
Pain - Neck
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Psychiatric disorders
Mood alteration - Anxiety
|
31.6%
12/38 • Number of events 12 • 1 year, 10 months
|
|
Psychiatric disorders
Confusion
|
18.4%
7/38 • Number of events 7 • 1 year, 10 months
|
|
Psychiatric disorders
Psychosis (hallucinations/delusions)
|
13.2%
5/38 • Number of events 6 • 1 year, 10 months
|
|
Psychiatric disorders
Mood alteration - Depression
|
10.5%
4/38 • Number of events 4 • 1 year, 10 months
|
|
General disorders
Dizziness
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
General disorders
Memory impairment
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
Psychiatric disorders
Mental status
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
General disorders
Syncope (fainting)
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other
|
36.8%
14/38 • Number of events 14 • 1 year, 10 months
|
|
Skin and subcutaneous tissue disorders
Pruritus/itching
|
15.8%
6/38 • Number of events 6 • 1 year, 10 months
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
10.5%
4/38 • Number of events 4 • 1 year, 10 months
|
|
Skin and subcutaneous tissue disorders
Rash: dermatitis associated with radiation - Chemoradiation
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
13.2%
5/38 • Number of events 5 • 1 year, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Hiccoughs (hiccups, singultus)
|
13.2%
5/38 • Number of events 5 • 1 year, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome (ARDS)
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion (non-malignant)
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory - Nose
|
13.2%
5/38 • Number of events 5 • 1 year, 10 months
|
|
General disorders
Hemorrhage/Bleeding - Other
|
10.5%
4/38 • Number of events 4 • 1 year, 10 months
|
|
Gastrointestinal disorders
Hemorrhage, GI - Lower GI NOS
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
Cardiac disorders
Cardiac General - Other
|
10.5%
4/38 • Number of events 5 • 1 year, 10 months
|
|
Cardiac disorders
Hypertension
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
Cardiac disorders
Hypotension
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
Cardiac disorders
Cardiac troponin T (cTnT)
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Renal and urinary disorders
Renal failure
|
15.8%
6/38 • Number of events 6 • 1 year, 10 months
|
|
Renal and urinary disorders
Renal/Genitourinary - Other
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)
|
13.2%
5/38 • Number of events 5 • 1 year, 10 months
|
|
Eye disorders
Dry eye syndrome
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
Eye disorders
Vision-blurred vision
|
7.9%
3/38 • Number of events 3 • 1 year, 10 months
|
|
Eye disorders
Ocular/Visual - Other
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
|
Eye disorders
Muscle weakness, generalized or specific area (not due to neuropathy) - Extraocular
|
5.3%
2/38 • Number of events 2 • 1 year, 10 months
|
Additional Information
Rami Komrokji, M.D.
H. Lee Moffitt Cancer Center and Research Institute
Phone: 813-745-4291
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place