Idarubicin and High-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia

• Sponsor: City of Hope Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00528398
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 111
• Locations: 2
• Arm: 1
• Duration (Months): 255
• Patients Per Site: 55.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving idarubicin together with high-dose cytarabine works in treating patients with acute myeloid leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: cytarabine; Drug: idarubicin	Phase 2

Detailed Description

OBJECTIVES:

• Determine the complete remission rate (CR).

• Determine the proportion of patients who are bone marrow-positive at day 7 post-induction chemotherapy.

• Further evaluate the toxicity of this regimen.

OUTLINE: Patients receive cytarabine IV over 3 hours every 12 hours on days 1-4 and idarubicin IV over 5-10 minutes on days 1-3. Patients undergo bone marrow aspirate and biopsy 7 days after completion of induction chemotherapy. Patients with > 25% cellular biopsy or > 10% abnormal cells on aspirate receive 4 more doses of cytarabine and 1 dose of idarubicin.

Study Design

• Study Type: Interventional
• Actual Enrollment: 111 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial Utilizing Idarubicin in Combination With High Dose Ara-C for Induction Therapy for Adult Acute Myelogenous Leukemia (AML)
• Study Start Date: Sep 1, 1994
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (idarubicin, cytarabine) Patients receive cytarabine IV over 3 hours every 12 hours on days 1-4 and idarubicin IV over 5-10 minutes on days 1-3. Patients undergo bone marrow aspirate and biopsy 7 days after completion of induction chemotherapy. Patients with > 25% cellular biopsy or > 10% abnormal cells on aspirate receive 4 more doses of cytarabine and 1 dose of idarubicin.

Drug: cytarabine; Other Names: Cytosine Arabinoside Cytosar-U Depocyt ; Drug: idarubicin; Other Names: 4-demethoxydaunorubicin Idamycin Zavedos

Outcome Measures

Primary Outcome Measures

1. Complete Remission (CR) [7 days post completion of induction chemotherapy]

   The peripheral blood neutrophil count is >= 1.5 x 10^9 / L and platelets more than 100 x 10^9 / L. Leukemia blast cells are not present in the peripheral blood. The cellularity of the bone marrow is more than 20% with maturation of all cell lines. The bone marrow contains less than 5% blast cells, and Auer rods is not detectable.

Secondary Outcome Measures

1. Bone Marrow at Day 7 Post-Induction Chemotherapy [7 days post completion of induction chemotherapy]

   Bone marrow positive, negative cells at day 7 post-induction chemotherapy for leukemia (%)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Newly diagnosed acute myeloid leukemia (AML)

• Morphologic proof (bone marrow aspirate smears or touch prep of marrow biopsy) of disease

• FAB M0, M1, M2, M4, M5a, M5b, M6a, M6b, and M7 disease

• Previously untreated with radiotherapy or chemotherapy

• Patients with treatment-related leukemia are eligible even if they have received prior chemotherapy and radiotherapy

• Patients with prior myelodysplastic syndrome are eligible

• Extramedullary leukemia allowed

• AML with lymphoid markers allowed

Exclusion criteria:

• Blastic transformation of chronic myelogenous leukemia

• Biphenotypic leukemia

• FAB M3 disease (acute promyelocytic leukemia)

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 6 weeks

• Total bilirubin < 1.5 g/dL

• AST and ALT < 5 times upper limit of normal (ULN)

• Creatinine < 1.5 mg/dL OR creatinine clearance > 70 mL/min

• Ejection fraction ≥ 50% by MUGA unless decreased ejection fraction is secondary to leukemia infiltration

• HIV antibody-negative

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• See Disease Characteristics

• Prior hydroxyurea or corticosteroids allowed

• At least 48 hours since prior and no concurrent itraconazole or fluconazole

Exclusion criteria:

• More than 300 mg/m² of prior daunorubicin or equivalent dose of anthracycline

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner Good Samaritan Medical Center	Phoenix	Arizona	United States	85006
2	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000

Sponsors and Collaborators

• City of Hope Medical Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Anthony S. Stein, MD, City of Hope Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: City of Hope Medical Center
• ClinicalTrials.gov Identifier: NCT00528398
• Other Study ID Numbers: 93139; P30CA033572; CHNMC-93139; CHNMC-93139-94-03-1; CDR0000564537
• First Posted: Sep 12, 2007
• Last Update Posted: Feb 6, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by City of Hope Medical Center: adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); secondary acute myeloid leukemia; untreated adult acute myeloid leukemia
• Additional relevant MeSH terms: Leukemia; Cytarabine; Idarubicin

Study Results

Participant Flow

Arm/Group Title	Treatment (Idarubicin, Cytarabine)
Arm/Group Description	All patients were analyzed together.
Period Title: Overall Study
STARTED	111
COMPLETED	111
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Idarubicin, Cytarabine)
Arm/Group Description	All patients were analyzed together.
Overall Participants	111
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	43
Gender (Count of Participants)
Female	50 45%
Male	61 55%
Diagnosis (Count of Participants)
De Novo AML	80 72.1%
AML Secondary to Chemotherapy	6 5.4%
AML Evolved from MDS	25 22.5%

Outcome Measures

1. Primary Outcome

Title	Complete Remission (CR)
Description	The peripheral blood neutrophil count is >= 1.5 x 10^9 / L and platelets more than 100 x 10^9 / L. Leukemia blast cells are not present in the peripheral blood. The cellularity of the bone marrow is more than 20% with maturation of all cell lines. The bone marrow contains less than 5% blast cells, and Auer rods is not detectable.
Time Frame	7 days post completion of induction chemotherapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Idarubicin, Cytarabine)
Arm/Group Description	All patients were analyzed together.
Measure Participants	111
CR	77 69.4%
No CR	32 28.8%
Unknown	2 1.8%

2. Secondary Outcome

Title	Bone Marrow at Day 7 Post-Induction Chemotherapy
Description	Bone marrow positive, negative cells at day 7 post-induction chemotherapy for leukemia (%)
Time Frame	7 days post completion of induction chemotherapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Idarubicin, Cytarabine)
Arm/Group Description	All patients were analyzed together.
Measure Participants	111
Positive for Leukemia	17 15.3%
Negative for Leukemia	90 81.1%
Unknown	4 3.6%

Adverse Events

Arm/Group Title	Treatment (Idarubicin, Cytarabine)
Arm/Group Description	All patients were analyzed together.
All Cause Mortality
	Treatment (Idarubicin, Cytarabine)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Idarubicin, Cytarabine)
	Affected / at Risk (%)	# Events
Total	51/111 (45.9%)
Blood and lymphatic system disorders
Pancytopenia	10/111 (9%)	10
Thrombocytopenia	1/111 (0.9%)	1
Gastrointestinal disorders
Nausea	3/111 (2.7%)	3
Diarrhea	1/111 (0.9%)	1
Pancreatitis	1/111 (0.9%)	1
General disorders
Fever	20/111 (18%)	20
Hepatobiliary disorders
Liver	1/111 (0.9%)	1
Jaundice	1/111 (0.9%)	1
Infections and infestations
Infection	4/111 (3.6%)	4
Gingivitis	1/111 (0.9%)	1
Investigations
Edema/Anasarca	1/111 (0.9%)	1
Metabolism and nutrition disorders
Hypocalcemia	2/111 (1.8%)	2
Hypokalemia	1/111 (0.9%)	1
Hyperglycemia	1/111 (0.9%)	1
Musculoskeletal and connective tissue disorders
Back Pain	2/111 (1.8%)	2
Abdominal pain	2/111 (1.8%)	2
Pleuritic Pain	1/111 (0.9%)	1
Nervous system disorders
Headache	2/111 (1.8%)	2
Paresthesia	1/111 (0.9%)	1
Respiratory, thoracic and mediastinal disorders
Lung	4/111 (3.6%)	4
Skin and subcutaneous tissue disorders
Skin	1/111 (0.9%)	1
Vascular disorders
Hypertension	3/111 (2.7%)	3
Hypotension	1/111 (0.9%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Idarubicin, Cytarabine)
	Affected / at Risk (%)	# Events
Total	95/111 (85.6%)
Blood and lymphatic system disorders
Hemorrhage	15/111 (13.5%)	15
Cardiac disorders
Heart	16/111 (14.4%)	16
Gastrointestinal disorders
Mucositis	43/111 (38.7%)	43
Nausea	75/111 (67.6%)	75
Vomiting	66/111 (59.5%)	66
Diarrhea	66/111 (59.5%)	66
General disorders
Fever	66/111 (59.5%)	66
Fatigue	6/111 (5.4%)	6
Chills	11/111 (9.9%)	11
Edema	8/111 (7.2%)	8
Hepatobiliary disorders
Liver	59/111 (53.2%)	59
Infections and infestations
Infection	56/111 (50.5%)	56
Metabolism and nutrition disorders
Hypocalcemia	7/111 (6.3%)	7
Hypokalemia	6/111 (5.4%)	6
Nervous system disorders
Anxiety	10/111 (9%)	10
Headache	24/111 (21.6%)	24
Psychiatric disorders
Insomnia	9/111 (8.1%)	9
Renal and urinary disorders
Renal	22/111 (19.8%)	22
Respiratory, thoracic and mediastinal disorders
Lung	32/111 (28.8%)	32
Skin and subcutaneous tissue disorders
Skin	70/111 (63.1%)	70

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.