Gemcitabine and Mitoxantrone in Treating Patients With Relapsed Acute Myeloid Leukemia

This study has been terminated.
(If </= 5 of the initial 18 patients had a CR, the study would be stopped. Only 5 patients (21%) of 24 enrolled patients had a CR so the study was terminated.)
National Cancer Institute (NCI)
Duke University
Information provided by (Responsible Party):
The Cleveland Clinic Identifier:
First received: December 20, 2005
Last updated: August 30, 2015
Last verified: August 2015

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.

Condition Intervention Phase
Drug: Gemcitabine Hydrochloride
Drug: Mitoxantrone Hydrochloride
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Gemcitabine/ Mitoxantrone in Patients With Acute Myeloid Leukemia in First Relapse

Resource links provided by NLM:

Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • Complete Response Rate [ Time Frame: 4 Weeks ] [ Designated as safety issue: No ]
    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).

  • Duration of the First Complete Response [ Time Frame: 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease-free and Overall Survival [ Time Frame: 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. ] [ Designated as safety issue: No ]
  • Laboratory Correlates: Immunohistochemistry [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    Percentage of patients who had a moderate-strong (2-3+) expression of multidrug resistance (MDR) genes by immunohistochemistry.

    • Multidrug resistance gene 1 (MDR1)
    • Equilibrative nucleoside transporter 2(SLC29A2)

  • White Blood Cell Count at Time of Relapse [ Time Frame: After a CR is achieved, patient will be followed at 3 month intervals for disease progression, typically for up to 5 years. ] [ Designated as safety issue: No ]
  • Percentage of Patients Making it to Bone Marrow Transplant. [ Time Frame: After completion of protocol therapy ] [ Designated as safety issue: No ]
    Assessing the number of patients who were able to have protocol treatment and have a bone marrow transplant after treatment.

Enrollment: 24
Study Start Date: January 2006
Study Completion Date: July 2011
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Gemcitabine Hydrochloride
10 mg/m2/ min IV for 12 hours
Other Name: Gemcitabine
Drug: Mitoxantrone Hydrochloride
12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3
Other Name: Mitoxantrone

Detailed Description:



  • Determine the complete response (CR) rate (CR and incomplete blood count recovery (CRi)) of patients with acute myeloid leukemia in first relapse treated with gemcitabine hydrochloride and mitoxantrone hydrochloride.


  • Evaluate disease free and overall survival of patients with acute myeloid leukemia in first relapse treated with this particular chemotherapy regimen.
  • Assess hematologic and non-hematologic toxicity associated with this regimen.
  • Assess laboratory correlates of drug resistance in patients with relapsed acute myeloid leukemia.
  • Assess the percentage of patients receiving subsequent bone marrow transplantation.

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Bone marrow examination or peripheral blood analysis confirming active acute myeloid leukemia by WHO criteria

    • No M3 acute myeloid leukemia
  • Not a candidate for allogenic bone marrow transplantation
  • Patient must be in first relapse after having received induction chemotherapy

    • Received 1 or 2 courses with remission lasting at least 1 month
  • Patients with chloromas or leukemia cutis are eligible
  • No evidence of leptomeningeal involvement


  • 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

    • Liver enzymes ≥ 2.5 are acceptable if physician documents that it is secondary to the disease
  • 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


  • Previous treatment related toxicities should be resolved to grade 1 or better
  • No other investigational agents within 14 days prior to the start of study
  • No chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to start of study
  • No major surgery within 2 weeks prior to start of study
  • At least two weeks must have elapsed since the conclusion of radiation therapy and the start of gemcitabine hydrochloride, provided the acute effects of radiation treatment have been resolved
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00268242

United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
National Cancer Institute (NCI)
Duke University
Study Chair: Anjali Advani, MD The Cleveland Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: The Cleveland Clinic Identifier: NCT00268242     History of Changes
Other Study ID Numbers: CASE-CCF-7725, P30CA043703, CASE-CCF-7725
Study First Received: December 20, 2005
Results First Received: June 3, 2015
Last Updated: August 30, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by The Cleveland Clinic:
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)
recurrent adult acute myeloid leukemia
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Central Nervous System Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Sensory System Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors processed this record on October 09, 2015