Bortezomib in Treating Patients With High-Risk Acute Myeloid Leukemia in Remission

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01465386
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 40
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial studies how well bortezomib works in treating patients with high-risk acute myeloid leukemia (AML) in remission. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia	Drug: bortezomib	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine if bortezomib when given as maintenance therapy for six months post-remission can improve the progression-free survival (PFS) rate by 50% (or 4.5 months) in first remission patients with high-risk AML.

SECONDARY OBJECTIVES:

1. To determine the overall survival (OS) after maintenance therapy with bortezomib in first remission AML patients.

2. To assess the safety and tolerability of subcutaneous (SC) administration of bortezomib given as maintenance therapy to first remission AML patients.

OUTLINE:

Patients receive bortezomib SC on days 1, 8, 15 and 22. Treatment repeats every 35 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks, every 3 months for 2 years, and then annually for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Subcutaneous Bortezomib as Maintenance Therapy for Patients With High-risk Acute Myeloid Leukemia in Remission
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Jan 28, 2014
• Actual Study Completion Date: Mar 2, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (enzyme inhibitor therapy) Patients receive bortezomib SC on days 1, 8, 15 and 22. Treatment repeats every 35 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: bortezomib; Given SC; Other Names: LDP 341 MLN341 VELCADE

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) [Up to 2 years]

   Number of days from enrollment to recurrence of acute myeloid leukemia as determined by the reappearance of blasts in the blood or marrow

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• All adults with first remission AML including those with prior myelodysplasia (MDS)/AML, therapy-related AML, AML with trilineage dysplasia (AML-TLD), and AML with adverse cytogenetics

• History of histopathologically documented AML that is currently in first remission with the presence of 5% or less blasts by morphology and/or flow cytometry from a bone marrow aspirate and/or biopsy obtained within 14 days of enrollment

• Patients must start therapy between 3-8 weeks after receiving their last prior therapy (either induction therapy or consolidation therapy)

• Patients may receive up to 4 courses of remission consolidation therapy (e.g., cytarabine) prior to enrollment

• Normal kidney and liver function with serum creatinine =< 2.0 mg/dl

• Total bilirubin =< 1.5 upper limit of normal (ULN)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

• Male subjects, even if surgically sterilized (i.e., status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse

• Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse

• Understand and voluntarily sign the informed consent form for this study

Exclusion Criteria:

• Favorable AML features defined as the following:

• t(8;21)(q22;q22); RUNX1-RUNX1T1

• inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11

• Mutated NPM1 without FLT3-ITD (normal karyotype)

• Mutated CEBPA (normal karyotype)

• Persistent clinically significant non-hematological toxicity that is > Grade 1 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4 from prior chemotherapy

• Active uncontrolled infection

• Known infection with human immunodeficiency virus (HIV)

• Medical condition, serious concurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize patient safety or interfere with the objectives of the study

• Uncontrolled or significant cardiovascular disease, including:

• Uncontrolled angina or myocardial infarction within 6 months

• Current or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, unless a screening echocardiogram (ECHO) or Multiple Gate Acquisition Scan (MUGA) performed within 1 month prior to study screening results in a left ventricular ejection fraction (LVEF) that is >= 45% (or institutional lower limit of normal value)

• Prolonged QTc interval (> 450 msec)

• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

• Patient has a platelet count of < 30,000 within 3 days before enrollment

• Patient has an absolute neutrophil count of < 300 within 3 days before enrollment

• Patient has >= Grade 2 peripheral neuropathy

• Patient has hypersensitivity to bortezomib, boron, or mannitol

• Female patients who are lactating or have a positive urine pregnancy test during the screening; pregnancy testing is not required for postmenopausal or surgically sterilized women

• Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: John Pagel, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT01465386
• Other Study ID Numbers: 2529.00; NCI-2011-03115
• First Posted: Nov 4, 2011
• Last Update Posted: Apr 4, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes; Bortezomib

Study Results

Participant Flow

Arm/Group Title	Treated Patients
Arm/Group Description	Patients receive bortezomib SC on days 1, 8, 15 and 22. Treatment repeats every 35 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. bortezomib: Given SC
Period Title: Overall Study
STARTED	6
COMPLETED	2
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Treatment (Enzyme Inhibitor Therapy)
Arm/Group Description	Patients receive bortezomib SC on days 1, 8, 15 and 22. Treatment repeats every 35 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. bortezomib: Given SC
Overall Participants	6
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	78
Sex: Female, Male (Count of Participants)
Female	3 50%
Male	3 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	6 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 16.7%
White	5 83.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	Number of days from enrollment to recurrence of acute myeloid leukemia as determined by the reappearance of blasts in the blood or marrow
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Patient who began maintenance treatment with bortezomib after induction of remission

Arm/Group Title	Treated Patients
Arm/Group Description	Patients receive bortezomib SC on days 1, 8, 15 and 22. Treatment repeats every 35 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. bortezomib: Given SC
Measure Participants	6
Median (Full Range) [days]	107

Adverse Events

Time Frame	1 year
Arm/Group Title	Treatment (Enzyme Inhibitor Therapy)
Arm/Group Description	Patients receive bortezomib SC on days 1, 8, 15 and 22. Treatment repeats every 35 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. bortezomib: Given SC
All Cause Mortality
	Treatment (Enzyme Inhibitor Therapy)
	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)
Serious Adverse Events
	Treatment (Enzyme Inhibitor Therapy)
	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)
Gastrointestinal disorders
Cholechystitis	1/6 (16.7%)	1
Nervous system disorders
Altered Mental Status	1/6 (16.7%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Enzyme Inhibitor Therapy)
	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)
Nervous system disorders
Peripheral neuropathy	1/6 (16.7%)	1

Limitations/Caveats

Difficulty finding patients willing or available to come in to clinic for weekly injections for the duration of the study. Study was ultimately closed because of slow enrollment.

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.