Trial Outcomes & Findings for Gemcitabine and Mitoxantrone in Treating Patients With Relapsed Acute Myeloid Leukemia (NCT NCT00268242)

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

4 Weeks

Results posted on

2018-02-22

Participant Flow

Patients were treated at the Cleveland Clinic or Duke University Medical Center during the years 2005-2008.

If \</= 5 of the initial 18 patients enrolled achieved a CR, the study would be stopped. Accrual was not halted while follow-up of the first 18 evaluable patients was under way. Therefore, 24 patients were enrolled. Only 5 patients (21%) achieved a CR and therefore, the study was terminated.

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	24
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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
Overall Study Death	1

Baseline Characteristics

Gemcitabine and Mitoxantrone in Treating Patients With Relapsed Acute Myeloid Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gemcitabine + Mitoxantrone n=24 Participants 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
Age, Continuous	51 years n=93 Participants
Sex: Female, Male Female	10 Participants n=93 Participants
Sex: Female, Male Male	14 Participants n=93 Participants
Region of Enrollment United States	24 participants n=93 Participants

PRIMARY outcome

Timeframe: 4 Weeks

Population: A total of 5 patients (21%) achieved a complete response.

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).

Outcome measures

Outcome measures
Measure	Gemcitabine + Mitoxantrone n=24 Participants 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
Complete Response Rate	5 participants

PRIMARY outcome

Timeframe: 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.

Population: Only 5 patients had a complete response, therefore on 5 patients were analyzed for this measure.

Outcome measures

Outcome measures
Measure	Gemcitabine + Mitoxantrone n=5 Participants 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
Duration of the First Complete Response	7.3 months Interval 2.9 to 30.3

SECONDARY outcome

Timeframe: 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.

Population: 1 patient died on day 1 of protocol therapy (secondary to complications from AML).

Outcome measures

Outcome measures
Measure	Gemcitabine + Mitoxantrone n=24 Participants 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
Disease-free and Overall Survival Patients dead >30 days post-tx, after relapse	18 participants
Disease-free and Overall Survival Patients dead >30 days post-tx, no relapse	1 participants
Disease-free and Overall Survival Patients alive with no evidence of disease relapse	4 participants
Disease-free and Overall Survival Patient death on Day 1 of Protocol Therapy	1 participants

SECONDARY outcome

Timeframe: Baseline

Population: 23 of 24 patients had available blocks for Immunohistochemical (IHC) analysis; Participants with the SLC29A2 Gene Expression (n=22)

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)

Outcome measures

Outcome measures
Measure	Gemcitabine + Mitoxantrone n=23 Participants 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
Laboratory Correlates: Immunohistochemistry Participants with GSTP1 Gene Expression	70 percentage of participants
Laboratory Correlates: Immunohistochemistry Participants with MDR1 Gene Expression	22 percentage of participants
Laboratory Correlates: Immunohistochemistry Participants with SLC29A2 Gene Expression	55 percentage of participants
Laboratory Correlates: Immunohistochemistry Participants with MRP1 Gene Expression	43 percentage of participants
Laboratory Correlates: Immunohistochemistry Participants with LRP1 Gene Expression	35 percentage of participants

SECONDARY outcome

Timeframe: After a CR is achieved, patient will be followed at 3 month intervals for disease progression, typically for up to 5 years.

Outcome measures

Outcome measures
Measure	Gemcitabine + Mitoxantrone n=24 Participants 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
White Blood Cell Count at Time of Relapse	3450 cells per microliter Interval 800.0 to

SECONDARY outcome

Timeframe: After completion of protocol therapy

Assessing the number of patients who were able to have protocol treatment and have a bone marrow transplant after treatment.

Outcome measures

Outcome measures
Measure	Gemcitabine + Mitoxantrone n=24 Participants 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
Percentage of Patients Making it to Bone Marrow Transplant.	8 percentage of Patients completed a BMT

Adverse Events

Gemcitabine + Mitoxantrone

Serious events: 24 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Gemcitabine + Mitoxantrone n=24 participants at risk 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
Infections and infestations Fever or Infection	83.3% 20/24 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.
Skin and subcutaneous tissue disorders Rash	79.2% 19/24 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.
Gastrointestinal disorders Nausea	66.7% 16/24 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.
General disorders Pain	66.7% 16/24 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.
Gastrointestinal disorders Mucositis	58.3% 14/24 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.
Gastrointestinal disorders Diarrhea	58.3% 14/24 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.
Musculoskeletal and connective tissue disorders Fatigue	50.0% 12/24 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.
Gastrointestinal disorders Abdominal Pain	37.5% 9/24 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.

Other adverse events

Adverse event data not reported

Additional Information

Anjali S. Advani, MD

The Cleveland Clinic

Phone: 216-445-5330

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place