Safety Study Evaluating Intravenous Infusions of Tigecycline to Treat Acute Myeloid Leukemia

Sponsor

University Health Network, Toronto (Other)

Overall Status

Completed

CT.gov ID

NCT01332786

Collaborator

University of Kansas (Other), Memorial Sloan Kettering Cancer Center (Other), University of California, Los Angeles (Other)

Enrollment

Locations

Arm

46.1

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether tigecycline is safe and which dosage is most effective in the treatment of patients with acute myeloid leukemia.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Tigecycline	Phase 1

Detailed Description

Relapsed and refractory hematologic malignancies have poor responses to standard therapy and are associated with a poor prognosis. For example, relapsed acute myeloid leukemia (AML) is a highly aggressive and resistant disease, particularly when associated with first complete response (CR) duration of less than 12 months. Thus, there is an urgent need for new agents in relapsed and refractory hematologic malignancies such as acute leukemia. In elderly patients, where the tolerance of aggressive induction therapy is often poor and curative options such as bone marrow transplantation HSCT are not available, the need for effective non-aggressive drug regimens for AML is even greater.

Tigecycline is a glycylcycline derivative of tetracycline. Tigecycline is currently indicated for the treatment of complicated skin and skin structure infections, and complicated intra-abdominal infections. This clinical trial is a Phase I dose escalation study of tigecycline in patients with relapsed or refractory AML or those with newly diagnosed disease not eligible for induction chemotherapy.

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1 Study Evaluating the Tolerance and Biologic Activity of Intravenous Infusions of Tigecycline in Patients With Relapsed or Refractory AML

Study Start Date :

Mar 1, 2011

Actual Primary Completion Date :

Oct 1, 2014

Actual Study Completion Date :

Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tigecycline	Drug: Tigecycline Dosage Form: one-hour intravenous infusion Dosage levels, frequency, duration: (3-week cycles) Level 1: 50 mg daily x 10 doses; 1 week rest Level 2: 100 mg daily x 10 doses; 1 week rest Level 3: 150 mg daily x 10 doses; 1 week rest Level 4: 200 mg daily x 10 doses 1 week rest Level 5: 250 mg daily x 10 doses; 1 week rest Level 6: 300 mg daily x 10 doses; 1 week rest Level 7: 350 mg daily x 10 doses; 1 week rest Other Names: Tygacil

Arm

Intervention/Treatment

Experimental: Tigecycline

Drug: Tigecycline

Dosage Form: one-hour intravenous infusion Dosage levels, frequency, duration: (3-week cycles) Level 1: 50 mg daily x 10 doses; 1 week rest Level 2: 100 mg daily x 10 doses; 1 week rest Level 3: 150 mg daily x 10 doses; 1 week rest Level 4: 200 mg daily x 10 doses 1 week rest Level 5: 250 mg daily x 10 doses; 1 week rest Level 6: 300 mg daily x 10 doses; 1 week rest Level 7: 350 mg daily x 10 doses; 1 week rest

Other Names:

Tygacil

Outcome Measures

Primary Outcome Measures

Toxicity evaluated according to CTCAE version 4.03 [Reviewed at each visit and assessed at the end of each 3-week cycle]

Secondary Outcome Measures

Response rate assessment of tigecycline through laboratory assessments [Assessed at the end of each 3-week cycle for the study duration]
Bone marrow assessment, absolute neutrophil count, platelet counts

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age >18 years
Diagnosis of relapsed or refractory AML for which all potentially curative or standard salvage therapy options have been exhausted; OR AML without prior treatment who are not eligible for induction chemotherapy as defined as age > or equal to 80 or age > 70 with poor risk cytogenetics (3 or more abnormalities, -5/del(5q), 3q abnormalities, or -7) or stable co-morbidities that would preclude induction chemotherapy such as LVEF less than 40% and/or DlCO less than 60% expected
ECOG 0-2 performance status
Biochemical values within the following range
Serum creatinine <2x upper limit of normal
Total bilirubin <1.5x upper limit of normal
AST and ALT <2x upper limit of normal
Recovery from non-hematologic toxicity from prior chemotherapy
Able and willing to provide informed consent

Exclusion Criteria:

Allergy to tetracycline or minocycline
Uncontrolled intercurrent illness such as uncontrolled diabetes or active uncontrolled infection
Active systemic bacterial, fungal, or viral infection
Concomitant use of linezolid or chloramphenicol that are known to inhibit mitochondrial protein synthesis
Pregnant or breast feeding
Known active CNS involvement with AML
Neurologic symptoms related to uncontrolled illnesses or unexplained causes
Psychiatric illness that would limit compliance with study
Receiving systemic chemotherapy other than hydroxyurea to control circulating blast counts. Concomitant hydroxyurea is permitted, but only in the first cycle of therapy
Prior therapy with tigecycline as an anti-cancer therapy or any use of the drug in the last month
Use of other investigational anti-leukemic therapy within 14 days of registration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles	Los Angeles	California	United States	90095
2	The University of Kansas Medical Center	Kansas City	Kansas	United States	66160
3	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9