- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00275080
Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia
A Phase 1 Study of Vorinostat (Suberoylanilide Hydroxamic Acid; SAHA) in Combination With Decitabine in Patients With Advanced Solid Tumors, Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia in Blast Crisis
This phase I trial is studying the side effects and best dose of vorinostat when given together with decitabine in treating patients with advanced solid tumors or relapsed or refractory non-Hodgkin's lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia.
Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving vorinostat together with decitabine may kill more cancer cells.
Study Overview
Status
Conditions
- Recurrent Adult Acute Myeloid Leukemia
- Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
- Nodal Marginal Zone B-cell Lymphoma
- Recurrent Adult Burkitt Lymphoma
- Recurrent Adult Diffuse Large Cell Lymphoma
- Recurrent Adult Diffuse Mixed Cell Lymphoma
- Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
- Recurrent Adult Immunoblastic Large Cell Lymphoma
- Recurrent Adult Lymphoblastic Lymphoma
- Recurrent Grade 1 Follicular Lymphoma
- Recurrent Grade 2 Follicular Lymphoma
- Recurrent Grade 3 Follicular Lymphoma
- Recurrent Mantle Cell Lymphoma
- Recurrent Marginal Zone Lymphoma
- Splenic Marginal Zone Lymphoma
- Unspecified Adult Solid Tumor, Protocol Specific
- 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)
- Secondary Acute Myeloid Leukemia
- Untreated Adult Acute Myeloid Leukemia
- Recurrent Adult Acute Lymphoblastic Leukemia
- Recurrent Small Lymphocytic Lymphoma
- Stage III Adult Burkitt Lymphoma
- Stage III Adult Diffuse Large Cell Lymphoma
- Stage III Adult Diffuse Mixed Cell Lymphoma
- Stage III Adult Diffuse Small Cleaved Cell Lymphoma
- Stage III Grade 1 Follicular Lymphoma
- Stage III Grade 2 Follicular Lymphoma
- Stage III Grade 3 Follicular Lymphoma
- Stage III Mantle Cell Lymphoma
- Stage III Marginal Zone Lymphoma
- Stage III Small Lymphocytic Lymphoma
- Stage IV Adult Burkitt Lymphoma
- Stage IV Adult Diffuse Large Cell Lymphoma
- Stage IV Adult Diffuse Mixed Cell Lymphoma
- Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
- Stage IV Grade 1 Follicular Lymphoma
- Stage IV Grade 2 Follicular Lymphoma
- Stage IV Grade 3 Follicular Lymphoma
- Stage IV Mantle Cell Lymphoma
- Stage IV Marginal Zone Lymphoma
- Stage IV Small Lymphocytic Lymphoma
- Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
- Stage IV Adult Immunoblastic Large Cell Lymphoma
- Stage IV Adult Lymphoblastic Lymphoma
- Stage III Adult Lymphoblastic Lymphoma
- Untreated Adult Acute Lymphoblastic Leukemia
- Stage III Adult Immunoblastic Large Cell Lymphoma
- Blastic Phase Chronic Myelogenous Leukemia
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. Establish the maximum tolerated dose and recommended phase II dose of vorinostat in conjunction with decitabine in patients with advanced solid tumors or relapsed or refractory non-Hodgkin's lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia in blast crisis.
SECONDARY OBJECTIVES:
I. Identify the minimal effective dose of vorinostat in conjunction with decitabine that will lead to DNA demethylation, histone acetylation, and gene reactivation with tolerable toxicity in these patients.
II. Determine the pharmacokinetic profiles of vorinostat and decitabine in these patients. Correlate pharmacokinetic profiles of vorinostat and decitabine with toxicity and biological activity in these patients.
III. Assess the antitumor activity of vorinostat and decitabine in these patients.
OUTLINE: This is a parallel group, multicenter, dose-escalation study of vorinostat. Patients are stratified according to disease (solid tumors or non-Hodgkin's lymphoma [NHL] vs hematological malignancies).
Patients receive 1 of 2 dosing regimens.
Regimen 1 (sequential dosing): Patients receive oral vorinostat two or three times daily on days 6-21 or days 6-12 (patients with solid tumors or NHL only) and decitabine IV over 1 hour on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Regimen 2 (concurrent dosing): Patients receive oral vorinostat two or three times daily on days 1-21, days 1-14 (patients with hematological malignancies only), or two times daily on days 1-12 (patients with solid tumors or NHL only) and decitabine IV over 1 hour on days 1-5.
Courses repeat every 28 days or 21 days (patients with hematological malignancies only) in the absence of disease progression or unacceptable toxicity. In both groups, cohorts of 3-6 patients receive escalating doses of vorinostat until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The dose level just below MTD would be declared the recommended phase II dose (RPTD). Up to 10 patients are treated at the RPTD. After completion of study treatment, patients are followed at 4 weeks.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Ontario
-
Hamilton, Ontario, Canada, L8V 5C2
- Juravinski Cancer Centre at Hamilton Health Sciences
-
Hamilton, Ontario, Canada, L8S 4L8
- Chedoke-McMaster Hospitals
-
Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Hospital Phase 2 Consortium
-
Toronto, Ontario, Canada, M5G 2M9
- University Health Network-Princess Margaret Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Diagnosis of 1 of the following:
Confirmed relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) or chronic myelogenous leukemia in blast crisis (CML-BC)
- Patients with acute promyelocytic leukemia who have relapsed while on tretinoin allowed
- Patients with previously untreated AML who refuse induction chemotherapy allowed
- Patients who are not candidates for aggressive management (those that have medical conditions that prevent the administration of standard curative chemotherapy or those who require an allogeneic bone marrow transplantation for curative therapy but lack an appropriate donor) are allowed
- Histologically or cytologically confirmed relapsed or refractory non-Hodgkin's lymphoma (NHL)
Histologically confirmed solid tumor that is metastatic or unresectable or for which standard curative or palliative measures do not exist or are no longer effective
- Clinically or radiologically documented disease
- Patients whose only evidence of disease is tumor marker elevation are not eligible
Patients with AML, ALL, or CML-BC who have cerebral spinal fluid involvement may be included
- May be treated with intrathecal cytarabine and/or methotrexate prior to and/or during the study
- No known brain metastases in patients with solid tumors or NHL
- ECOG performance status 0-2
- Karnofsky 60-100%
- Life expectancy > 12 weeks for patients with solid tumors (including non-Hodgkin's lymphoma) and 6 weeks for patients with hematological malignancies
Patients with solid tumors (including NHL) must also have normal marrow function as defined below:
- Leukocytes ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelets ≥ 100,000/mm^3
- Creatinine ≤ 150 μmol/L
- Creatinine clearance ≥ 60 mL/min
- Bilirubin normal
- AST/ALT ≤ 2.5 times upper limit of normal (ULN)
- Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control or abstinence) prior to study entry and for the duration of study participation
- Not pregnant or nursing
- Negative pregnancy test
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or other agents used in study
- Able to take oral medications
- Patients who have a clinical or radiological diagnosis of bowel obstruction are ineligible
- No ongoing or active infection
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No psychiatric illness/social situations that would limit compliance with study requirements
- No other uncontrolled intercurrent illness
- No limitation on the number or types of prior therapy
At least 3 weeks since prior radiotherapy, chemotherapy (6 weeks for nitrosoureas or mitomycin C), or molecularly targeted agents
- Exceptions may be made for low-dose, non-myelosuppressive radiotherapy
- At least 2 weeks since prior valproic acid or any other histone deacetylase inhibitor
- Must have recovered from prior therapy
- Patients with hematological malignancies may receive hydroxyurea until 24 hours prior to starting study medications
- Previous surgery is permitted provided that wound healing has occurred
- No prior decitabine
- No other concurrent investigational agents
- No other concurrent investigational or commercial agents or therapies administered with the intent to treat the patient's malignancy
- No HIV-positive patients receiving combination antiretroviral therapy
No concurrent prophylactic hematopoietic growth factors (e.g. filgrastim [G-CSF], sargramostim [GM-CSF], thrombopoietin, or epoetin alfa)
- Hematopoietic growth factors colony stimulating factors for the treatment of cytopenia may be permitted at the discretion of the principal investigator
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (enzyme inhibitor, chemotherapy)
Regimen 1 (sequential dosing): Patients receive oral vorinostat two or three times daily on days 6-21 or days 6-12 (patients with solid tumors or NHL only) and decitabine IV over 1 hour on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen 2 (concurrent dosing): Patients receive oral vorinostat two or three times daily on days 1-21, days 1-14 (patients with hematological malignancies only), or two times daily on days 1-12 (patients with solid tumors or NHL only) and decitabine IV over 1 hour on days 1-5. |
Given IV
Other Names:
Given orally
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose and recommended phase II dose of vorinostat and decitabine
Time Frame: Course 1
|
Graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
|
Course 1
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Minimal effective dose of vorinostat in combination with decitabine by bone marrow and/or peripheral blood (for leukemia)
Time Frame: Baseline and between days 3-10
|
Baseline and between days 3-10
|
|
Pharmacokinetics of vorinostat in conjunction with decitabine
Time Frame: Days 1-15
|
Measured by peripheral blood.
Performed by high-performance liquid chromatography (HPLC).
Estimated by taking the mean concentration one hour after administration per patient on days 1 and 5 and estimating the mean, median and range over all patients.
|
Days 1-15
|
Antitumor activity
Time Frame: Every 4 weeks for leukemia and every 8 weeks for solid tumors or NHL
|
Measured by Response Evaluation Criteria In Solid Tumors (RECIST), NCI-international working group (IWG), and NCI criteria.
|
Every 4 weeks for leukemia and every 8 weeks for solid tumors or NHL
|
Methylation status of gene promoter regions and gene expression
Time Frame: Baseline and between days 3-10
|
Measured by bone marrow and/or peripheral blood.
|
Baseline and between days 3-10
|
Altered response of leukemic cells to PPAr and RAR ligands
Time Frame: Baseline and between days 3-8
|
Collected by bone marrow and/or peripheral blood (for leukemia)
|
Baseline and between days 3-8
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Karen Yee, Princess Margaret Hospital Phase 2 Consortium
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Virus Diseases
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- DNA Virus Infections
- Neoplastic Processes
- Tumor Virus Infections
- Epstein-Barr Virus Infections
- Herpesviridae Infections
- Leukemia, B-Cell
- Cell Transformation, Neoplastic
- Carcinogenesis
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Recurrence
- Lymphoma, Non-Hodgkin
- Burkitt Lymphoma
- Lymphoma, Mantle-Cell
- Lymphoma, B-Cell, Marginal Zone
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Lymphoma, Large-Cell, Immunoblastic
- Plasmablastic Lymphoma
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Blast Crisis
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Histone Deacetylase Inhibitors
- Decitabine
- Azacitidine
- Vorinostat
Other Study ID Numbers
- NCI-2009-00092 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U01CA132123 (U.S. NIH Grant/Contract)
- 6869 (CTEP)
- PMH-PHL-046
- CDR0000456473
- NCI-6869
- PHL-046 (Other Identifier: Princess Margaret Hospital Phase 2 Consortium)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Recurrent Adult Acute Myeloid Leukemia
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) | Adult Acute Myeloid Leukemia in Remission | Childhood Acute Myeloid Leukemia in Remission | Recurrent... and other conditionsUnited States
-
Alison WalkerCompletedRecurrent Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | 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... and other conditionsUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)Approved for marketingRecurrent Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | 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... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Recurrent Adult Acute Lymphoblastic Leukemia | Untreated Adult Acute Lymphoblastic LeukemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingRecurrent Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | 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... and other conditionsUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...CompletedRecurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid LeukemiaUnited States
-
University of Maryland, BaltimoreHematologics, IncRecruitingAcute Myeloid Leukemia Recurrent | Acute Myeloid Leukemia, Adult | Acute Myeloid Leukemia, Relapsed, AdultUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Untreated Adult Acute Myeloid LeukemiaUnited States
-
National Cancer Institute (NCI)TerminatedRecurrent Adult Acute Myeloid Leukemia | Untreated Adult Acute Myeloid LeukemiaUnited States
-
Bhavana BhatnagarCTI BioPharmaCompletedRecurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
Clinical Trials on decitabine
-
Otsuka Beijing Research InstituteRecruitingMyelodysplastic SyndromesChina
-
Astex Pharmaceuticals, Inc.CompletedAcute Myeloid Leukemia | Myelodysplastic Syndromes | Chronic Myelomonocytic LeukemiaUnited States, Canada, Spain, Hungary, Austria, Czechia, France, Germany, Italy, United Kingdom
-
Chinese PLA General HospitalRecruitingHodgkin Lymphoma | Anti-PD-1 Antibody ResistantChina
-
Roswell Park Cancer InstituteNational Comprehensive Cancer NetworkRecruitingCastration-Resistant Prostate Carcinoma | Stage IV Prostate Cancer AJCC v8 | Stage IVA Prostate Cancer AJCC v8 | Stage IVB Prostate Cancer AJCC v8United States
-
Shandong UniversityUnknownMyelodysplastic SyndromesChina
-
M.D. Anderson Cancer CenterGenentech, Inc.; Astex Pharmaceuticals, Inc.RecruitingChronic Myelomonocytic Leukemia | Myelodysplastic SyndromeUnited States
-
M.D. Anderson Cancer CenterRecruitingAcute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
M.D. Anderson Cancer CenterActive, not recruitingRecurrent Acute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Recurrent Acute Biphenotypic Leukemia | Refractory Acute Biphenotypic LeukemiaUnited States
-
Eisai Inc.TerminatedMyelodysplastic SyndromesUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI); Astex Pharmaceuticals, Inc.RecruitingChronic Phase Chronic Myelogenous Leukemia | Philadelphia Chromosome Positive | BCR-ABL1 Positive Chronic Myelogenous Leukemia | BCR-ABL1 PositiveUnited States