Gemcitabine and Mitoxantrone in Treating Patients With Relapsed Acute Myeloid Leukemia

NCT00268242 | Terminated Phase 2 Results

• 2 other identifiers: CASE-CCF-7725P30CA043703
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Leukemia

Keywords

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)

Outcome Measures

Primary Outcomes (2)

• 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.

Secondary Outcomes (4)

• 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

  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.

  After completion of protocol therapy

Study Arms (1)

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.

Drug: Gemcitabine Hydrochloride; Drug: Mitoxantrone Hydrochloride

Interventions

Gemcitabine Hydrochloride DRUG

10 mg/m2/ min IV for 12 hours

Also known as: Gemcitabine

Gemcitabine + Mitoxantrone

Mitoxantrone Hydrochloride DRUG

12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3

Also known as: Mitoxantrone

Gemcitabine + Mitoxantrone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * 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 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 * 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 PRIOR CONCURRENT THERAPY: * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• The Cleveland Clinic: lead
• National Cancer Institute (NCI): collaborator
• Duke University: collaborator

Study Sites (2)

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Leukemia; Congenital Abnormalities; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Monocytic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute

Interventions

Gemcitabine; Mitoxantrone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds

Limitations and Caveats

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

Results Point of Contact

• Title: Anjali S. Advani, MD
• Organization: The Cleveland Clinic

advania@ccf.org

216-445-5330

Study Officials

• Anjali Advani, MD

  The Cleveland Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2005
• First Posted: December 22, 2005
• Study Start: January 1, 2006
• Primary Completion: August 1, 2010
• Study Completion: July 1, 2011
• Last Updated: February 22, 2018
• Results First Posted: October 5, 2015

Record last verified: 2015-08

Locations

US (2)