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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA043703 | U.S. NIH Grant/Contract | View source | |
| CASE-CCF-7725 | Other Identifier | Cleveland Clinic |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| Duke University | OTHER |
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine and mitoxantrone, 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 gemcitabine together with mitoxantrone works in treating patients with relapsed acute myeloid leukemia.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is an open-label, multicenter study.
Patients receive gemcitabine hydrochloride IV over 12 hours on day 1 and mitoxantrone hydrochloride IV over 30-60 minutes on days 1, 2, and 3. After completion of a single course of therapy, patients who achieve a complete response may receive 1 additional course of therapy at the discretion of the treating physician.
After completion of study treatment, patients are followed periodically for survival.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Gemcitabine + Mitoxantrone | Experimental | Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gemcitabine Hydrochloride | Drug | 10 mg/m2/ min IV for 12 hours |
|
| Measure | Description | Time Frame |
|---|---|---|
| Complete Response Rate | Assumptions/ hypothesis: A Complete Response (CR) rate of 30% or less is unacceptable, and 50% or more is promising. A two-stage design will be used. Initially, 18 patients will be enrolled. If 5 or fewer achieve CR, the study will be stopped. Otherwise, an additional 22 patients will be accrued. Accrual was not halted while follow-up of the first 18 evaluable patients was under way. Therefore, 24 patients were enrolled. Four weeks is anticipated for observation for response. Only 5 patients (21%) achieved a CR and therefore, the study was terminated. Since response was assessed using the International Working Group criteria, a complete response was determined by Morphologic complete remission: A CR designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of ≥ 100,000/μL, a cytogenic CR and a morphologic CR with incomplete blood count recovery (CRi). | 4 Weeks |
| Duration of the First Complete Response | After a CR is achieved, patients are followed at 3 month intervals for disease progression and survival. If a patient has disease progression after achieving a CR, survival will be captured at 6 month intervals, typically for up to 5 years. |
| Measure | Description | Time Frame |
|---|---|---|
| Disease-free and Overall Survival | After a CR is achieved, patients are followed at 3 month intervals for disease progression and survival. If a patient has disease progression after achieving a CR, survival will be captured at 6 month intervals, typically for up to 5 years. | |
| Laboratory Correlates: Immunohistochemistry |
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DISEASE CHARACTERISTICS:
Bone marrow examination or peripheral blood analysis confirming active acute myeloid leukemia by WHO criteria
Not a candidate for allogenic bone marrow transplantation
Patient must be in first relapse after having received induction chemotherapy
Patients with chloromas or leukemia cutis are eligible
No evidence of leptomeningeal involvement
PATIENT CHARACTERISTICS:
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
Liver enzymes (total bilirubin, aspartate aminotransferase (AST) and ALT) ≤ 2.5 times the upper limits of normal
Serum creatinine ≤ 3 mg/dL
No poorly controlled medical conditions that would seriously complicate compliance with this study
No other active primary malignancy other than carcinoma in situ of the cervix or basal cell carcinoma of the skin
No New York Heart Association grade III or IV cardiac problems, defined as congestive heart failure or myocardial infarction within 6 months prior to start of study
Pregnant or nursing women are ineligible
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study participation
No documented history of human immunodeficiency virus (HIV) infection
No history of chronic liver disease
Ejection fraction ≥ 45%
No significant history of non-compliance to medical regimens or inability to give reliable informed consent
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Anjali Advani, MD | The Cleveland Clinic | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke Comprehensive Cancer Center | Durham | North Carolina | 27710 | United States | ||
| Cleveland Clinic Taussig Cancer Center |
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Patients were treated at the Cleveland Clinic or Duke University Medical Center during the years 2005-2008.
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| ID | Title | Description |
|---|---|---|
| FG000 | Gemcitabine + Mitoxantrone | Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3. Gemcitabine Hydrochloride: 10 mg/m2/ min IV for 12 hours Mitoxantrone Hydrochloride: 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Gemcitabine + Mitoxantrone | Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3. Gemcitabine Hydrochloride: 10 mg/m2/ min IV for 12 hours Mitoxantrone Hydrochloride: 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Complete Response Rate | Assumptions/ hypothesis: A Complete Response (CR) rate of 30% or less is unacceptable, and 50% or more is promising. A two-stage design will be used. Initially, 18 patients will be enrolled. If 5 or fewer achieve CR, the study will be stopped. Otherwise, an additional 22 patients will be accrued. Accrual was not halted while follow-up of the first 18 evaluable patients was under way. Therefore, 24 patients were enrolled. Four weeks is anticipated for observation for response. Only 5 patients (21%) achieved a CR and therefore, the study was terminated. Since response was assessed using the International Working Group criteria, a complete response was determined by Morphologic complete remission: A CR designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of ≥ 100,000/μL, a cytogenic CR and a morphologic CR with incomplete blood count recovery (CRi). | A total of 5 patients (21%) achieved a complete response. | Posted | Number | participants | 4 Weeks |
|
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All Adverse Event (AE) / Serious Adverse Event (SAE) data grades were included together in data reporting; there was no differentiation between AEs and SAEs and no unexpected toxicities were seen. Since all grades were reported together, they are being listed as Serious for that reason.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Gemcitabine + Mitoxantrone | Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3. Gemcitabine Hydrochloride: 10 mg/m2/ min IV for 12 hours Mitoxantrone Hydrochloride: 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fever or Infection | Infections and infestations | Systematic Assessment |
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If </= 5 of 1st 18 pts had a CR, study would stop (otherwise, another 22 pts would be accrued). Study would stop if >4 of 1st 10 or 10 of 1st 25 pts had unacceptable toxicity per protocol & Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anjali S. Advani, MD | The Cleveland Clinic | 216-445-5330 | advania@ccf.org |
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| ID | Term |
|---|---|
| D007938 | Leukemia |
| D000013 | Congenital Abnormalities |
| D015470 | Leukemia, Myeloid, Acute |
| D015479 | Leukemia, Myelomonocytic, Acute |
| D007948 | Leukemia, Monocytic, Acute |
| D004915 | Leukemia, Erythroblastic, Acute |
| D007947 | Leukemia, Megakaryoblastic, Acute |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000093542 | Gemcitabine |
| D008942 | Mitoxantrone |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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| Mitoxantrone Hydrochloride | Drug | 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3 |
|
|
Percentage of patients who had a moderate-strong (2-3+) expression of multidrug resistance (MDR) genes by immunohistochemistry.
|
| Baseline |
| White Blood Cell Count at Time of Relapse | After a CR is achieved, patient will be followed at 3 month intervals for disease progression, typically for up to 5 years. |
| Percentage of Patients Making it to Bone Marrow Transplant. | Assessing the number of patients who were able to have protocol treatment and have a bone marrow transplant after treatment. | After completion of protocol therapy |
| Cleveland |
| Ohio |
| 44195 |
| United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG000 | Gemcitabine + Mitoxantrone | Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m^2/day I.V. on days 1, 2, and 3. Gemcitabine Hydrochloride: 10 mg/m2/ min IV for 12 hours Mitoxantrone Hydrochloride: 12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3 |
|
|
| Secondary | Disease-free and Overall Survival | 1 patient died on day 1 of protocol therapy (secondary to complications from AML). | Posted | Number | participants | After a CR is achieved, patients are followed at 3 month intervals for disease progression and survival. If a patient has disease progression after achieving a CR, survival will be captured at 6 month intervals, typically for up to 5 years. |
|
|
|
| Secondary | Laboratory Correlates: Immunohistochemistry | Percentage of patients who had a moderate-strong (2-3+) expression of multidrug resistance (MDR) genes by immunohistochemistry.
| 23 of 24 patients had available blocks for Immunohistochemical (IHC) analysis; Participants with the SLC29A2 Gene Expression (n=22) | Posted | Number | percentage of participants | Baseline |
|
|
|
| Secondary | White Blood Cell Count at Time of Relapse | Posted | Median | Full Range | cells per microliter | After a CR is achieved, patient will be followed at 3 month intervals for disease progression, typically for up to 5 years. |
|
|
|
| Primary | Duration of the First Complete Response | Only 5 patients had a complete response, therefore on 5 patients were analyzed for this measure. | Posted | Median | Full Range | months | After a CR is achieved, patients are followed at 3 month intervals for disease progression and survival. If a patient has disease progression after achieving a CR, survival will be captured at 6 month intervals, typically for up to 5 years. |
|
|
|
| Secondary | Percentage of Patients Making it to Bone Marrow Transplant. | Assessing the number of patients who were able to have protocol treatment and have a bone marrow transplant after treatment. | Posted | Number | percentage of Patients completed a BMT | After completion of protocol therapy |
|
|
|
| 24 |
| 24 |
| 0 |
| 24 |
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Mucositis | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Fatigue | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
|
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| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007951 | Leukemia, Myeloid |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D011743 |
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D000880 | Anthraquinones |
| D000095322 | Anthrones |
| D000873 | Anthracenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011809 | Quinones |
| D011083 | Polycyclic Compounds |
| Title | Measurements |
|---|---|
|
| Patients dead >30 days post-tx, after relapse |
|
| Title | Measurements |
|---|---|
|
| Participants with LRP1 Gene Expression |
|
| Participants with MDR1 Gene Expression |
|