A Phase I Trial Of 17-Allylaminogeldanamycin (17-AAG) And PS341 In Advanced Malignancies
Phase 1
18 Years
N/A
18 Years
N/A
Not Enrolling
Both
Adult Grade III Lymphomatoid Granulomatosis, AIDS-related Peripheral/Systemic Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, 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 Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, 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 Adult Hodgkin Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Adult T-cell Leukemia/Lymphoma, Stage III Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome, 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 Adult Hodgkin Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Adult T-cell Leukemia/Lymphoma, Stage IV Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome, Stage IV Small Lymphocytic Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific, Waldenström Macroglobulinemia
Both
Adult Grade III Lymphomatoid Granulomatosis, AIDS-related Peripheral/Systemic Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, 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 Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, 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 Adult Hodgkin Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Adult T-cell Leukemia/Lymphoma, Stage III Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome, 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 Adult Hodgkin Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Adult T-cell Leukemia/Lymphoma, Stage IV Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome, Stage IV Small Lymphocytic Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific, Waldenström Macroglobulinemia
Trial Information
A Phase I Trial Of 17-Allylaminogeldanamycin (17-AAG) And PS341 In Advanced Malignancies
OBJECTIVES:
I. Determine the dose-limiting toxicity and maximum tolerated dose of
17-N-allylamino-17-demethoxygeldanamycin (17-AAG) (tanespimycin) and bortezomib in patients
with advanced solid tumors or lymphomas (Accrual for Lymphoma Patients Closed as of
11/27/09).
II. Determine changes in biomarkers (e.g., HSP70, client proteins, and ubiquitination of
proteins) in peripheral blood mononuclear cells and tumor specimens from patients with
advanced solid tumors or lymphomas (Accrual for Lymphoma Patients Closed as of 11/27/09)
treated with this regimen.
III. Determine responses in patients treated with this regimen. IV. Determine the toxic
effects of this regimen in these patients.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive tanespimycin intravenously (IV) over 1-2 hours and bortezomib IV over 3-5
seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of
tanespimycin and bortezomib 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. Once the MTD is determined, at least 12 additional patients are
treated as above* at the MTD.
NOTE: *Bortezomib is not administered on day 1 of course 1 only. Patients are followed at 3
months.
Inclusion Criteria:
- Histologically confirmed solid tumor or lymphomas (Accrual for Lymphoma Patients
Closed as of 11/27/09)
- Refractory to standard treatment OR no standard treatment that is potentially
curative or capable of prolonging life expectancy exists
- Tumor amenable to biopsy (patients accrued at the MTD only)
- No CNS metastases
- Performance status - ECOG 0-2
- At least 12 weeks
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9.0 g/dL
- Bilirubin ≤ 2 times upper limit of normal (ULN)
- AST ≤ 2.5 times ULN
- Alkaline phosphatase ≤ 2 times ULN (5 times ULN if due to liver involvement)
- Creatinine ≤ 2 times ULN
- QTc < 500 msec for men (470 msec for women)
- LVEF > 40% by echocardiogram
- Ejection fraction normal by echocardiogram (for patients who have received prior
anthracycline therapy)
- No cardiac symptoms ≥ grade 2
- No New York Heart Association class III or IV heart failure
- No myocardial infarction within the past year
- No active ischemic heart disease within the past year
- No congenital long QT syndrome
- No left bundle branch block
- No history of uncontrolled dysrhythmias or requiring antiarrhythmic drugs
- No history of cardiac toxicity after receiving anthracyclines (e.g., doxorubicin
hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or
carmustine)
- No poorly controlled angina
- No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular
fibrillation ≥ 3 beats in a row)
- No other significant cardiac disease
- Pulse oximetry at rest and exercise < 88% (per Medicare guidelines)
- No pulmonary symptoms ≥ grade 2
- No significant pulmonary disease requiring oxygen supplementation or causing a severe
limitation in activity
- No symptomatic pulmonary disease requiring medication including any of the following:
- Dyspnea on or off exertion
- Paroxysmal nocturnal dyspnea
- Oxygen requirement and significant pulmonary disease, including chronic
obstructive/restrictive pulmonary disease
- No home oxygen use that meets the Medicare criteria
- No history of pulmonary toxicity after receiving anthracyclines (e.g., doxorubicin
hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or
carmustine)
- No seizure disorder
- No sensory peripheral neuropathy > grade 1
- No neuropathic pain of any etiology
- Patients with residual peripheral neuropathy ≤ grade 1 due to oxaliplatin
therapy allowed
- No uncontrolled infection
- No prior serious allergic reaction to eggs
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Willing to return to Mayo Clinic Rochester, Mayo Clinic Arizona, or Mayo Clinic
Florida for follow up
- More than 4 weeks since prior immunotherapy or biologic therapy
- No concurrent prophylactic colony-stimulating factors
- No concurrent immunotherapy, biologic therapy, or gene therapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- No other concurrent chemotherapy
- Concurrent steroids (at a stable dose for ≥ 4 weeks) for comorbid conditions (e.g.,
adrenal insufficiency or rheumatoid arthritis) allowed
- More than 4 weeks since prior radiotherapy
- No prior radiotherapy that potentially included the heart in the field (e.g., mantle)
or chest
- No prior radiotherapy to > 25% of bone marrow
- No prior radiopharmaceuticals
- No concurrent radiotherapy
- Recovered from prior therapy
- More than 8 weeks since prior UCN-01
- No concurrent warfarin
- Low molecular weight heparin allowed
- No concurrent medications that prolong or may prolong QTc interval
- No other concurrent investigational therapy
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
MTD of tanespimycin in combination with bortezomib in the treatment of solid tumors
Outcome Description:
Defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of the solid tumor patients (at least 2 of a maximum of 6 new patients).
Outcome Time Frame:
At 3 weeks
Safety Issue:
Yes
Principal Investigator
Charles Erlichman
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00043
NCT ID:
NCT00096005
Start Date:
November 2004
Completion Date:
Related Keywords:
- Adult Grade III Lymphomatoid Granulomatosis
- AIDS-related Peripheral/Systemic Lymphoma
- Anaplastic Large Cell Lymphoma
- Angioimmunoblastic T-cell Lymphoma
- 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 Grade III Lymphomatoid Granulomatosis
- Recurrent Adult Hodgkin Lymphoma
- Recurrent Adult Immunoblastic Large Cell Lymphoma
- Recurrent Adult Lymphoblastic Lymphoma
- Recurrent Adult T-cell Leukemia/Lymphoma
- Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
- Recurrent Grade 1 Follicular Lymphoma
- Recurrent Grade 2 Follicular Lymphoma
- Recurrent Grade 3 Follicular Lymphoma
- Recurrent Mantle Cell Lymphoma
- Recurrent Marginal Zone Lymphoma
- Recurrent Mycosis Fungoides/Sezary Syndrome
- 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 Adult Hodgkin Lymphoma
- Stage III Adult Immunoblastic Large Cell Lymphoma
- Stage III Adult Lymphoblastic Lymphoma
- Stage III Adult T-cell Leukemia/Lymphoma
- Stage III Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome
- 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 Adult Hodgkin Lymphoma
- Stage IV Adult Immunoblastic Large Cell Lymphoma
- Stage IV Adult Lymphoblastic Lymphoma
- Stage IV Adult T-cell Leukemia/Lymphoma
- Stage IV Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome
- Stage IV Small Lymphocytic Lymphoma
- Unspecified Adult Solid Tumor, Protocol Specific
- Waldenström Macroglobulinemia
- Burkitt Lymphoma
- Hodgkin Disease
- Immunoblastic Lymphadenopathy
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, T-Cell
- Leukemia-Lymphoma, Adult T-Cell
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, Large B-Cell, Diffuse
- Lymphoma, Non-Hodgkin
- Lymphomatoid Granulomatosis
- Waldenstrom Macroglobulinemia
- Mycoses
- Mycosis Fungoides
- Sezary Syndrome
- Lymphoma, B-Cell
- Lymphoma, Large-Cell, Immunoblastic
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Lymphoma, T-Cell
- Lymphoma, T-Cell, Cutaneous
- Lymphoma, Large-Cell, Anaplastic
- Lymphoma, B-Cell, Marginal Zone
- Lymphoma, Extranodal NK-T-Cell
- Lymphoma, Mantle-Cell
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
