UPCI 13-066: Phase II Clofarabine and Cytarabine for Newly Diagnosed Acute Myeloid Leukemia

• Sponsor: University of Pittsburgh (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01960387
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 17
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The combination of clofarabine and cytarabine is an effective and reasonably well-tolerated treatment regimen in patients with either relapsed/refractory or newly diagnosed AML. For this prospective study, we propose the use of clofarabine and cytarabine for second course induction therapy for patients with persistent AML after treatment with an anthracycline and cytarabine.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Clofarabine; Drug: Cytarabine	Phase 2

Detailed Description

The primary objective of this prospective study is to evaluate the efficacy (i.e., complete response rate) of clofarabine and cytarabine as second course therapy for the treatment of AML. The secondary objectives are to assess the treatment-related toxicities, to determine the overall and relapse-free survival for patients with AML who are treated with this regimen, and to evaluate potential factors that are predictive of response.

The investigational nature and objective of this study, the procedures involved and their associated risks, potential benefits, and potential alternative therapies will be explained to the patient, and a signed informed consent document will be obtained. Once consented, eligible patients will be treated by the acute leukemia service on the University of Pittsburgh Cancer Institute inpatient unit.

Prior to the start of chemotherapy, patients will receive dexamethasone and ondansetron as pre-medication. Clofarabine will then be administered as intravenous infusion on days 1 through 5. Patients will be monitored closely with vital signs. Cytarabine will then be given as intravenous infusion, starting 3 (maximum of 4) hours after the completion of clofarabine administration on days 1 through 5.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Clofarabine and Cytarabine for Patients With Newly Diagnosed Acute Myeloid Leukemia Who Have Persistent Disease After Treatment With an Anthracycline and Cytarabine
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Clofarabine and Cytarabine Clofarabine will be administered as a 1-hour (range: 1 hour minimum to 2 hours maximum) intravenous infusion at a dose of 40mg/m2 daily on days 1 through 5. Cytarabine at a dose of 1g/m2 daily will then be given as a 2-hour intravenous infusion, starting 3 hours after the completion of clofarabine administration on days 1 through 5.

Drug: Clofarabine; Clofarabine will be administered as a 1-hour (range: 1 hour minimum to 2 hours maximum) intravenous infusion at a dose of 40mg/m2 daily on days 1 through 5.; Other Names: Clolar antimetabolite Purine nucleoside analog ; Drug: Cytarabine; Cytarabine at a dose of 1g/m2 daily will be given as a 2-hour intravenous infusion, starting 3 hours after the completion of clofarabine administration on days 1 through 5.; Other Names: Cytosine arabinoside antimetabolite Pyrimidine analog

Outcome Measures

Primary Outcome Measures

1. Complete Clinical Response [Between 14 and 28 days from start of study treatment]

   Number of patients with newly diagnosed Acute Myeloid Leukemia who achieved Complete Response to therapy as determined by bone marrow biopsy evaluation. A CR designation required that the patient achieved a morphologic leukemia-free state and an absolute neutrophil count greater than or equal to 1.0 x 10^9/l, a platelet count greater than or equal to 100 x 10^9/l, and no evidence of extramedullary disease.

Secondary Outcome Measures

1. Overall Survival [Up to 24 months]

   Number of months of survival for newly diagnosed Acute Myeloid Leukemia patients treated with Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day).

2. Relapse Free Survival [Up to 24 months]

   Number of months of relapse free survival for newly diagnosed Acute Myeloid Leukemia patients treated with Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day).

3. Predictive Factors for Response to Treatment. [Up to 1 year]

   Evaluation of potential factors that are predictive of clinical response in newly diagnosed Acute Myeloid Leukemia patients treated with Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with newly diagnosed AML based on the World Health Organization classification who have persistent disease after their first course treatment with an anthracycline and cytarabine

2. Able to understand and have the ability to provide written informed consent

3. Patients over 18 years of age

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

5. Left ventricular ejection fraction (LVEF) ≥ 50%

6. Negative urine pregnancy test for all females

7. All subjects must agree to use an effective method of contraception while receiving the study drugs

Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia

2. Relapsed AML

3. Prior use of clofarabine

4. Previous allogeneic or autologous hematopoietic cell transplantation

5. Impaired liver function (serum total bilirubin > 2.0 mg/dL, alanine aminotransferase and aspartate aminotransferase ≥ 4 x the upper limit of normal)

6. Impaired renal function (serum creatinine ≥ 2.0 mg/dL)

7. Uncontrolled or life-threatening infection that is not responding to antimicrobial therapy

8. History of a psychiatric disorder which may compromise compliance with the protocol or which does not allow for appropriate informed consent

9. Concurrent active malignancy; exceptions include patients who have been disease free for 5 years, patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, or patients with another malignancy that is indolent or definitively treated

10. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory or cardiac disease)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232

Sponsors and Collaborators

• University of Pittsburgh

Investigators

• Principal Investigator: Michael Boyiadzis, M.D., M.H.Sc, University of Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael Boyiadzis, Principal Investigator, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT01960387
• Other Study ID Numbers: UPCI 13-066
• First Posted: Oct 10, 2013
• Last Update Posted: Aug 2, 2016
• Last Verified: Jun 1, 2016

• Keywords provided by Michael Boyiadzis, Principal Investigator, University of Pittsburgh: AML; clofarabine; cytarabine; persistent AML; induction therapy
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Cytarabine; Clofarabine; Antimetabolites

Study Results

Participant Flow

Arm/Group Title	Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day)
Arm/Group Description	Patients with newly diagnosed Acute Myeloid Leukemia who received clofarabine administered as a 1-2 hour intravenous infusion at a dose of 40mg/m^2 daily plus cytarabine at a dose of 1g/m^2 daily, 2-4 hours maximum intravenous infusion starting 3-4 hours post completion of clofarabine administration on days 1 through 5.
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day)
Arm/Group Description	Patients with newly diagnosed Acute Myeloid Leukemia who received clofarabine administered as a 1-2 hour intravenous infusion at a dose of 40mg/m^2 daily plus cytarabine at a dose of 1g/m^2 daily, 2-4 hours maximum intravenous infusion starting 3-4 hours post completion of clofarabine administration on days 1 through 5.
Overall Participants	2
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	55
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%

Outcome Measures

1. Primary Outcome

Title	Complete Clinical Response
Description	Number of patients with newly diagnosed Acute Myeloid Leukemia who achieved Complete Response to therapy as determined by bone marrow biopsy evaluation. A CR designation required that the patient achieved a morphologic leukemia-free state and an absolute neutrophil count greater than or equal to 1.0 x 10^9/l, a platelet count greater than or equal to 100 x 10^9/l, and no evidence of extramedullary disease.
Time Frame	Between 14 and 28 days from start of study treatment

Outcome Measure Data

Analysis Population Description

Newly diagnosed Acute Myeloid Leukemia patients who received clofarabine (1-2 hour intravenous infusion of 40mg/m2 daily dose) plus cytarabine (2-4 hours maximum intravenous infusion of 1g/m2 daily dose) starting 3-4 hours post completion of clofarabine administration on days 1 through 5, who were evaluable for response by bone marrow biopsy.

Arm/Group Title	Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day)
Arm/Group Description	Clofarabine administered as a 1-2 hour intravenous infusion at a dose of 40mg/m^2 daily plus Cytarabine at a dose of 1g/m^2 daily, 2-4 hours maximum intravenous infusion starting 3-4 hours post completion of clofarabine administration on days 1 through 5.
Measure Participants	2
Number [participants]	2 100%

2. Secondary Outcome

Title	Overall Survival
Description	Number of months of survival for newly diagnosed Acute Myeloid Leukemia patients treated with Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day).
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Results data are not available due to low/insufficient subject accrual from early [trial] termination.

Arm/Group Title	Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day)
Arm/Group Description	Clofarabine administered as a 1-2 hour intravenous infusion at a dose of 40mg/m^2 daily plus Cytarabine at a dose of 1g/m^2 daily, 2-4 hours maximum intravenous infusion starting 3-4 hours post completion of clofarabine administration on days 1 through 5.
Measure Participants	0

3. Secondary Outcome

Title	Relapse Free Survival
Description	Number of months of relapse free survival for newly diagnosed Acute Myeloid Leukemia patients treated with Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day).
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Results data are not available due to low/insufficient subject accrual from early [trial] termination.

Arm/Group Title	Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day)
Arm/Group Description	Clofarabine administered as a 1-2 hour intravenous infusion at a dose of 40mg/m^2 daily plus Cytarabine at a dose of 1g/m^2 daily, 2-4 hours maximum intravenous infusion starting 3-4 hours post completion of clofarabine administration on days 1 through 5.
Measure Participants	0

4. Secondary Outcome

Title	Predictive Factors for Response to Treatment.
Description	Evaluation of potential factors that are predictive of clinical response in newly diagnosed Acute Myeloid Leukemia patients treated with Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day).
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Results data are not available due to low/insufficient subject accrual from early [trial] termination.

Arm/Group Title	Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day)
Arm/Group Description	Clofarabine administered as a 1-2 hour intravenous infusion at a dose of 40mg/m^2 daily plus Cytarabine at a dose of 1g/m^2 daily, 2-4 hours maximum intravenous infusion starting 3-4 hours post completion of clofarabine administration on days 1 through 5.
Measure Participants	0

Adverse Events

Arm/Group Title	Clofarabine (40mg/m2/Day) + Cytarabine (1g/m2/Day)
Arm/Group Description	Patients with Newly Diagnosed Acute Myeloid Leukemia who received clofarabine administered as a 1-2 hour intravenous infusion at a dose of 40mg/m2 daily plus cytarabine at a dose of 1g/m2 daily, 2-4 hours maximum intravenous infusion starting 3-4 hours post completion of clofarabine administration, on days 1 through 5.
All Cause Mortality
	Clofarabine (40mg/m2/Day) + Cytarabine (1g/m2/Day)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Clofarabine (40mg/m2/Day) + Cytarabine (1g/m2/Day)
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Blood and lymphatic system disorders
Febrile neutropenia	1/2 (50%)
Infections and infestations
Lung infection	1/2 (50%)
Other (Not Including Serious) Adverse Events
	Clofarabine (40mg/m2/Day) + Cytarabine (1g/m2/Day)
	Affected / at Risk (%)	# Events
Total	0/2 (0%)

Limitations/Caveats

Results data is not available for Overall Survival, Relapse-free Survival, or assessment of potential predictive factors for response to treatment, due to early termination leading to small numbers of subjects analyzed.

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.