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17-N-Allylamino-17-Demethoxygeldanamycin and Bortezomib in Treating Patients With Relapsed or Refractory Hematologic Cancer
This study has been completed.
First Received: February 7, 2005   Last Updated: July 23, 2008   History of Changes
Sponsors and Collaborators: Arthur G. James Cancer Hospital & Richard J. Solove Research Institute
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00103272
  Purpose

RATIONALE: Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving 17-N-allylamino-17-demethoxygeldanamycin together with bortezomib may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin and bortezomib in treating patients with relapsed or refractory hematologic cancer.


Condition Intervention Phase
Leukemia
Lymphoma
Small Intestine Cancer
Drug: bortezomib
Drug: tanespimycin
Phase I

MedlinePlus related topics: Cancer Intestinal Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma
Drug Information available for: 17-(Allylamino)-17-demethoxygeldanamycin Bortezomib IPI-504
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Study of PS-341 (Velcade™, Bortezomib) in Combination With 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Patients With Relapsed or Refractory Hematologic Malignancies

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 74
Study Start Date: May 2005
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) and bortezomib in patients with relapsed or refractory acute myeloid leukemia (AML), acute lymphoblastic leukemia, chronic lymphocytic lymphoma, or non-Hodgkin's lymphoma.
  • Determine the toxic effects and dose-limiting toxicity of this regimen in these patients.

Secondary

  • Determine the pharmacokinetics of 17-AAG alone and in combination with bortezomib in these patients.
  • Correlate FLT3 mutational status with leukemic cell response in patients with AML treated with this regimen.
  • Correlate Bcl-2 over-expression with response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study. Patients are stratified according to diagnosis (acute myeloid leukemia [AML] or acute lymphoblastic leukemia vs chronic lymphoctyic leukemia or non-Hodgkin's lymphoma [NHL]).

Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1-6 hours on days 1, 4, 8, and 11 and bortezomib IV over 3-5 seconds on days 4, 8, and 11 of course 1 and on days 1, 4, 8, and 11 of all subsequent courses. Treatment repeats every 21 days for 3-12 courses provided patient is receiving clinical benefit. Patients achieving objective response may discontinue therapy to undergo stem cell transplantation.

Cohorts of 3-6 patients with receive escalating doses of 17-AAG 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. After the MTD is determined, an additional 20 patients (10 per stratum with AML or follicular NHL) are enrolled and receive 17-AAG and bortezomib as above at the MTD.

PROJECTED ACCRUAL: A total of 56-74 patients (36-54 [18-27 per stratum] who undergo dose escalation and 20 [10 per stratum] treated at the maximum tolerated dose) will be accrued for this study within 1-2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed diagnosis of 1 of the following hematologic malignancies:

    • Acute myeloid leukemia or acute lymphoblastic leukemia

      • Not a candidate for potentially curative therapy
      • WBC ≤ 10,000/mm^3 OR WBC ≤ 40,000/mm^3 that is stable for 5 days (hydroxyurea allowed)
      • No acute promyelocytic leukemia
    • Non-Hodgkin's lymphoma (NHL), including 1 of the following subtypes:

      • Small lymphocytic lymphoma
      • Marginal zone lymphoma
      • Lymphoplasmacytic lymphoma
      • Follicular lymphoma
      • Mantle cell lymphoma
      • Diffuse large B-cell lymphoma
      • Anaplastic large cell lymphoma
      • Peripheral T-cell lymphoma
      • Extranodal NK/T cell lymphoma (nasal and nasal type)
      • Enteropathy-type T-cell lymphoma
      • Hepatosplenic T-cell lymphoma
      • Angioimmunoblastic T-cell lymphoma
      • Subcutaneous panniculitis-like T-cell lymphoma
    • Chronic lymphocytic leukemia (CLL)
  • Patients with NHL or CLL must meet the following criteria:

    • Ineligible for, or refused potentially curative stem cell transplantation
    • Transformed lymphoma/Richter's transformation, defined as the transformation of low-grade lymphoma, including follicular lymphoma, CLL, or small lymphocytic lymphoma to high-grade lymphoma (i.e., diffuse large cell lymphoma) allowed at time of transformation
    • Evidence of ≥ 50% bone marrow involvement at the time of enrollment OR tumor tissue accessible for biopsy (for patients enrolled after the maximum tolerated dose [MTD] is determined)
    • Absolute neutrophil count ≥ 1,000/mm^3
    • Platelet count ≥ 100,000/mm^3
  • Relapsed or refractory disease
  • Willing to undergo serial bone marrow biopsy (for patients enrolled after the MTD is determined)
  • No untreated or active CNS leukemia or lymphoma

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 12 weeks

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin ≤ 1.5 mg/dL
  • AST and ALT ≤ 2.5 times upper limit of normal

Renal

  • Creatinine ≤ 2.0 mg/dL

Cardiovascular

  • No uncontrolled cardiac disease
  • No New York Heart Association class III-IV symptomatic congestive heart failure
  • No unstable angina pectoris
  • No serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation > 3 beats in a row) within the past 6 months
  • No other uncontrolled cardiac arrhythmia or requiring antiarrhythmic drugs
  • 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
  • QTc ≥ 450 msec (for men) or 470 (for women) on ECG/EKG
  • No history of LVEF < 50% by MUGA or echocardiogram
  • Resting ejection fraction ≥ 50% by MUGA or echocardiogram
  • No prior history of cardiac toxicity after receiving anthracycline therapy (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, or mitoxantrone hydrochloride)

Pulmonary

  • No uncontrolled pulmonary disease
  • No symptomatic pulmonary disease requiring oxygen or medications
  • DLCO (i.e., oxygen diffusion capacity) ≥ 80% on pulmonary function testing
  • Resting and exercise oxygen saturation ≥ 90% by pulse oximetry
  • No ongoing pulmonary symptoms ≥ grade 2 including any of the following:

    • Dyspnea on or off exertion
    • Paroxysmal nocturnal dyspnea
    • Significant pulmonary disease including chronic obstructive or restrictive pulmonary disease
    • No prior history of pulmonary toxicity after bleomycin or carmustine
  • No Medicare requirement for home oxygen (e.g., Resting O_2 saturation ≥ 90% or desaturation to ≥ 90% with exertion)

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • No preexisting sensory or motor peripheral neuropathy ≥ grade 2
  • No history of allergic reaction to eggs
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • Prior stem cell transplantation for relapsed or refractory disease allowed
  • At least 2 weeks since prior immunotherapy and recovered

Chemotherapy

  • See Disease Characteristics
  • At least 2 weeks since prior chemotherapy (excluding hydroxyurea) and recovered
  • No other concurrent chemotherapy

Endocrine therapy

  • No concurrent routine corticosteroids except for treatment of other medical problems (e.g., pulmonary, rheumatologic, or adrenal disorders)

Radiotherapy

  • At least 2 weeks since prior radiotherapy and recovered
  • No prior radiotherapy that potentially included the heart in the field (e.g., mantle)
  • No prior history of chest radiation
  • No concurrent palliative radiotherapy

Surgery

  • Not specified

Other

  • At least 2 weeks since prior investigational therapy
  • Prior bortezomib allowed
  • No other concurrent commercial or investigational agents or therapies for the malignancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00103272

Locations
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210-1240
Sponsors and Collaborators
Arthur G. James Cancer Hospital & Richard J. Solove Research Institute
Investigators
Study Chair: Kristie A. Blum, MD Arthur G. James Cancer Hospital & Richard J. Solove Research Institute
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000409584, OSU-2004C0084, NCI-6520, OSU-0448
Study First Received: February 7, 2005
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00103272     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
recurrent adult acute lymphoblastic leukemia
refractory chronic lymphocytic leukemia
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)
recurrent adult acute myeloid leukemia
recurrent small lymphocytic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse large cell lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
recurrent adult T-cell leukemia/lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
Waldenstrom macroglobulinemia
small intestine lymphoma
recurrent mycosis fungoides/Sezary syndrome
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)

Study placed in the following topic categories:
Lymphoma, Mantle-Cell
Mantle Cell Lymphoma
Ileal Diseases
Follicular Lymphoma
Duodenal Neoplasms
Mycoses
Acute Erythroblastic Leukemia
Acute Myelocytic Leukemia
Acute Myeloid Leukemia, Adult
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Digestive System Neoplasms
Leukemia, Myeloid
Protease Inhibitors
Waldenstrom Macroglobulinemia
Leukemia, Erythroblastic, Acute
B-cell Lymphomas
Leukemia, T-Cell
Gastrointestinal Neoplasms
Lymphoma, Non-Hodgkin
Di Guglielmo's Syndrome
Lymphoma, T-Cell, Cutaneous
Leukemia, Monocytic, Acute
Leukemia, Lymphoid
Hematologic Neoplasms
Gastrointestinal Diseases
Acute Myelomonocytic Leukemia

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Antineoplastic Agents
Ileal Diseases
Duodenal Neoplasms
Leukemia
Neoplasms by Site
Ileal Neoplasms
Jejunal Diseases
Therapeutic Uses
Lymphoma
Duodenal Diseases
Jejunal Neoplasms
Immunoproliferative Disorders
Neoplasms by Histologic Type
Digestive System Neoplasms
Immune System Diseases
Bortezomib
Enzyme Inhibitors
Intestinal Diseases
Intestinal Neoplasms
Pharmacologic Actions
Protease Inhibitors
Lymphatic Diseases
Neoplasms
Digestive System Diseases
Gastrointestinal Neoplasms
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on May 07, 2009