Trial Outcomes & Findings for Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia (NCT NCT01342887)
NCT ID: NCT01342887
Last Updated: 2017-07-02
Results Overview
Determine the doses of mitoxantrone and etoposide that, when combined with CSA and pravastatin, meet minimum standards for both efficacy and toxicity and have the highest efficacy rate among several mitoxantrone and etoposide doses. Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
6 participants
Primary outcome timeframe
After completion of first 2 courses, up to 22 weeks
Results posted on
2017-07-02
Participant Flow
Participant milestones
| Measure |
Treatment (Immunosuppression, Enzyme Inhibitor, and Chemo)
Patients receive cyclosporine IV continuously on days 5-9. Patients also receive pravastatin sodium PO every 6 hours on days 1-10, etoposide IV continuously on days 5-9, and mitoxantrone hydrochloride IV continuously on days 5-9. Treatment repeats for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR/CRi may receive 2 additional courses in the absence of disease progression or unacceptable toxicity.
cyclosporine: Given IV
pravastatin sodium: Given PO
mitoxantrone hydrochloride: Given IV
etoposide: Given IV
bone marrow aspiration: Correlative studies
|
|---|---|
|
Overall Study
STARTED
|
6
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Treatment (Immunosuppression, Enzyme Inhibitor, and Chemo)
Patients receive cyclosporine IV continuously on days 5-9. Patients also receive pravastatin sodium PO every 6 hours on days 1-10, etoposide IV continuously on days 5-9, and mitoxantrone hydrochloride IV continuously on days 5-9. Treatment repeats for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR/CRi may receive 2 additional courses in the absence of disease progression or unacceptable toxicity.
cyclosporine: Given IV
pravastatin sodium: Given PO
mitoxantrone hydrochloride: Given IV
etoposide: Given IV
bone marrow aspiration: Correlative studies
|
|---|---|
|
Overall Study
Death
|
2
|
Baseline Characteristics
Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Baseline characteristics by cohort
| Measure |
Treatment (Immunosuppression, Enzyme Inhibitor, and Chemo)
n=6 Participants
Patients receive cyclosporine IV continuously on days 5-9. Patients also receive pravastatin sodium PO every 6 hours on days 1-10, etoposide IV continuously on days 5-9, and mitoxantrone hydrochloride IV continuously on days 5-9. Treatment repeats for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR/CRi may receive 2 additional courses in the absence of disease progression or unacceptable toxicity.
cyclosporine: Given IV
pravastatin sodium: Given PO
mitoxantrone hydrochloride: Given IV
etoposide: Given IV
bone marrow aspiration: Correlative studies
|
|---|---|
|
Age, Continuous
|
51 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: After completion of first 2 courses, up to 22 weeksDetermine the doses of mitoxantrone and etoposide that, when combined with CSA and pravastatin, meet minimum standards for both efficacy and toxicity and have the highest efficacy rate among several mitoxantrone and etoposide doses. Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Outcome measures
| Measure |
Treatment (Immunosuppression, Enzyme Inhibitor, and Chemo)
n=6 Participants
Patients receive cyclosporine IV continuously on days 5-9. Patients also receive pravastatin sodium PO every 6 hours on days 1-10, etoposide IV continuously on days 5-9, and mitoxantrone hydrochloride IV continuously on days 5-9. Treatment repeats for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR/CRi may receive 2 additional courses in the absence of disease progression or unacceptable toxicity.
cyclosporine: Given IV
pravastatin sodium: Given PO
mitoxantrone hydrochloride: Given IV
etoposide: Given IV
bone marrow aspiration: Correlative studies
|
|---|---|
|
Maximum Tolerated Doses Mitoxantrone Hydrochloride and Etoposide When Combined With Cyclosporine and Pravastatin Sodium
|
0 doses tolerated
|
SECONDARY outcome
Timeframe: After completion of first 2 courses, up to 22 weeksDescribe the disease-free survival of patients that achieve Complete Remission (CR)/CR with inadequate recovery of peripheral blood cell counts (CRi). Categorized according to criteria recommended by an International Working Group.
Outcome measures
| Measure |
Treatment (Immunosuppression, Enzyme Inhibitor, and Chemo)
n=6 Participants
Patients receive cyclosporine IV continuously on days 5-9. Patients also receive pravastatin sodium PO every 6 hours on days 1-10, etoposide IV continuously on days 5-9, and mitoxantrone hydrochloride IV continuously on days 5-9. Treatment repeats for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR/CRi may receive 2 additional courses in the absence of disease progression or unacceptable toxicity.
cyclosporine: Given IV
pravastatin sodium: Given PO
mitoxantrone hydrochloride: Given IV
etoposide: Given IV
bone marrow aspiration: Correlative studies
|
|---|---|
|
CR/CRi
CR
|
0 Participants
|
|
CR/CRi
CRi
|
0 Participants
|
|
CR/CRi
CR/CRi not achieved
|
6 Participants
|
SECONDARY outcome
Timeframe: Up to 4.5 yearsDescribe the disease-free survival of patients that achieve CR/CRi.
Outcome measures
| Measure |
Treatment (Immunosuppression, Enzyme Inhibitor, and Chemo)
n=6 Participants
Patients receive cyclosporine IV continuously on days 5-9. Patients also receive pravastatin sodium PO every 6 hours on days 1-10, etoposide IV continuously on days 5-9, and mitoxantrone hydrochloride IV continuously on days 5-9. Treatment repeats for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR/CRi may receive 2 additional courses in the absence of disease progression or unacceptable toxicity.
cyclosporine: Given IV
pravastatin sodium: Given PO
mitoxantrone hydrochloride: Given IV
etoposide: Given IV
bone marrow aspiration: Correlative studies
|
|---|---|
|
Disease-free Survival of Patients That Achieve CR/CRi
0-6month survival of those achieving CR/CRi
|
0 Participants
|
|
Disease-free Survival of Patients That Achieve CR/CRi
>6month survival of those achieving CR/CRi
|
0 Participants
|
|
Disease-free Survival of Patients That Achieve CR/CRi
Participants who do not achieve CR/CRi
|
6 Participants
|
SECONDARY outcome
Timeframe: At 28 daysEstimate the frequency and severity of regimen-associated toxicities, along with 28-day mortality after start of study treatment
Outcome measures
| Measure |
Treatment (Immunosuppression, Enzyme Inhibitor, and Chemo)
n=6 Participants
Patients receive cyclosporine IV continuously on days 5-9. Patients also receive pravastatin sodium PO every 6 hours on days 1-10, etoposide IV continuously on days 5-9, and mitoxantrone hydrochloride IV continuously on days 5-9. Treatment repeats for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR/CRi may receive 2 additional courses in the absence of disease progression or unacceptable toxicity.
cyclosporine: Given IV
pravastatin sodium: Given PO
mitoxantrone hydrochloride: Given IV
etoposide: Given IV
bone marrow aspiration: Correlative studies
|
|---|---|
|
Frequency and Severity of Regimen-associated Toxicities
Early death (within 28 days)
|
2 Participants
|
|
Frequency and Severity of Regimen-associated Toxicities
Experienced Dose-Limiting Toxicity
|
1 Participants
|
|
Frequency and Severity of Regimen-associated Toxicities
Persistent Disease
|
3 Participants
|
Adverse Events
Treatment (Immunosuppression, Enzyme Inhibitor, and Chemo)
Serious events: 5 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment (Immunosuppression, Enzyme Inhibitor, and Chemo)
n=6 participants at risk
Patients receive cyclosporine IV continuously on days 5-9. Patients also receive pravastatin sodium PO every 6 hours on days 1-10, etoposide IV continuously on days 5-9, and mitoxantrone hydrochloride IV continuously on days 5-9. Treatment repeats for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR/CRi may receive 2 additional courses in the absence of disease progression or unacceptable toxicity.
cyclosporine: Given IV
pravastatin sodium: Given PO
mitoxantrone hydrochloride: Given IV
etoposide: Given IV
bone marrow aspiration: Correlative studies
|
|---|---|
|
Infections and infestations
Sepsis
|
66.7%
4/6 • Number of events 4
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
16.7%
1/6 • Number of events 1
|
|
Renal and urinary disorders
Acute Kidney Injury
|
16.7%
1/6 • Number of events 1
|
Other adverse events
| Measure |
Treatment (Immunosuppression, Enzyme Inhibitor, and Chemo)
n=6 participants at risk
Patients receive cyclosporine IV continuously on days 5-9. Patients also receive pravastatin sodium PO every 6 hours on days 1-10, etoposide IV continuously on days 5-9, and mitoxantrone hydrochloride IV continuously on days 5-9. Treatment repeats for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR/CRi may receive 2 additional courses in the absence of disease progression or unacceptable toxicity.
cyclosporine: Given IV
pravastatin sodium: Given PO
mitoxantrone hydrochloride: Given IV
etoposide: Given IV
bone marrow aspiration: Correlative studies
|
|---|---|
|
Infections and infestations
Vancomycin-Resistant Enterococci Bacteremia
|
33.3%
2/6 • Number of events 2
|
|
Renal and urinary disorders
Acute Kidney Injury
|
50.0%
3/6 • Number of events 4
|
|
Nervous system disorders
Acute toxic-metabolic encephalopathy
|
16.7%
1/6 • Number of events 1
|
|
Psychiatric disorders
Altered Mental Status
|
66.7%
4/6 • Number of events 4
|
|
Blood and lymphatic system disorders
Anemia
|
16.7%
1/6 • Number of events 1
|
|
Renal and urinary disorders
Anuria
|
16.7%
1/6 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
16.7%
1/6 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
16.7%
1/6 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Blanched buttocks
|
16.7%
1/6 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasms
|
16.7%
1/6 • Number of events 1
|
|
Injury, poisoning and procedural complications
Bruising
|
16.7%
1/6 • Number of events 1
|
|
Renal and urinary disorders
Burning sensation during urination
|
16.7%
1/6 • Number of events 1
|
|
Injury, poisoning and procedural complications
Burning sensation during infusion
|
50.0%
3/6 • Number of events 3
|
|
Infections and infestations
Cellulitis
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Chest pain
|
33.3%
2/6 • Number of events 2
|
|
General disorders
Chills
|
33.3%
2/6 • Number of events 2
|
|
Infections and infestations
Coagulase Negative Staphylococcus Bacteremia
|
16.7%
1/6 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
3/6 • Number of events 4
|
|
Nervous system disorders
Dizziness
|
33.3%
2/6 • Number of events 2
|
|
Infections and infestations
E. Coli Urinary Tract Infection
|
16.7%
1/6 • Number of events 1
|
|
Ear and labyrinth disorders
Ear pain to palpitation
|
16.7%
1/6 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Periobital Edema
|
33.3%
2/6 • Number of events 2
|
|
Hepatobiliary disorders
Transaminitis
|
16.7%
1/6 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
50.0%
3/6 • Number of events 3
|
|
Gastrointestinal disorders
Esophageal pain
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Fatigue
|
83.3%
5/6 • Number of events 5
|
|
Injury, poisoning and procedural complications
Febrile nonhemolytic transfusion reaction
|
16.7%
1/6 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Scalp rash
|
16.7%
1/6 • Number of events 1
|
|
Nervous system disorders
Headache
|
50.0%
3/6 • Number of events 3
|
|
Gastrointestinal disorders
Heartburn
|
16.7%
1/6 • Number of events 1
|
|
Renal and urinary disorders
Hematuria
|
33.3%
2/6 • Number of events 2
|
|
Investigations
Blood bilirubin increased
|
33.3%
2/6 • Number of events 2
|
|
Vascular disorders
Hypertension
|
100.0%
6/6 • Number of events 6
|
|
Metabolism and nutrition disorders
Hypokalemia
|
66.7%
4/6 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyponatremia
|
33.3%
2/6 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
16.7%
1/6 • Number of events 1
|
|
Vascular disorders
Hypotension
|
33.3%
2/6 • Number of events 2
|
|
General disorders
Hypothermia
|
16.7%
1/6 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
16.7%
1/6 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
16.7%
1/6 • Number of events 1
|
|
Investigations
Jaundice
|
16.7%
1/6 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Leg Pain
|
50.0%
3/6 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Leukemia cutis
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
Anorexia
|
100.0%
6/6 • Number of events 7
|
|
General disorders
Malaise
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
33.3%
2/6 • Number of events 2
|
|
Gastrointestinal disorders
Mucositis oral
|
100.0%
6/6 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Multifocal pneumonia
|
33.3%
2/6 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
100.0%
6/6 • Number of events 6
|
|
Psychiatric disorders
Nervousness/agitation
|
16.7%
1/6 • Number of events 1
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
66.7%
4/6 • Number of events 7
|
|
Gastrointestinal disorders
Oral Thrush
|
16.7%
1/6 • Number of events 1
|
|
Reproductive system and breast disorders
Pain on left areola, superficial
|
16.7%
1/6 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Pain, right axillary area
|
33.3%
2/6 • Number of events 2
|
|
Cardiac disorders
Palpitation
|
16.7%
1/6 • Number of events 1
|
|
Blood and lymphatic system disorders
Pancytopenia
|
50.0%
3/6 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
33.3%
2/6 • Number of events 2
|
|
Immune system disorders
Pulmonary Aspergillosis
|
16.7%
1/6 • Number of events 1
|
|
Infections and infestations
Rash, chest
|
50.0%
3/6 • Number of events 3
|
|
Nervous system disorders
Restlessness
|
16.7%
1/6 • Number of events 1
|
|
Renal and urinary disorders
Rhabdomyolysis
|
16.7%
1/6 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Rhinovirus
|
33.3%
2/6 • Number of events 2
|
|
Infections and infestations
Sinus Infection
|
16.7%
1/6 • Number of events 1
|
|
Cardiac disorders
Tachycardia
|
100.0%
6/6 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
33.3%
2/6 • Number of events 2
|
|
General disorders
Edema, bilateral hand and feet
|
33.3%
2/6 • Number of events 2
|
|
General disorders
Edema, face
|
16.7%
1/6 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnea
|
33.3%
2/6 • Number of events 2
|
|
Nervous system disorders
Tremors
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Gait disturbance
|
16.7%
1/6 • Number of events 1
|
|
Infections and infestations
Viral upper respiratory infection
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Volume Retention
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
2/6 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Weakness
|
66.7%
4/6 • Number of events 4
|
|
Investigations
Weight Gain
|
16.7%
1/6 • Number of events 1
|
|
Psychiatric disorders
Withdrawn/Unwilling to communicate
|
16.7%
1/6 • Number of events 1
|
|
Eye disorders
Extraocular muscle paresis, worsening
|
16.7%
1/6 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place