Tanespimycin in Treating Young Patients With Recurrent or Refractory Leukemia or Solid Tumors

Brief Title

Tanespimycin in Treating Young Patients With Recurrent or Refractory Leukemia or Solid Tumors

Official Title

A Multicenter Phase I Trial of 17-N-allylamino-17-demethoxy Geldanamycin (17-AAG, NSC #330507) in Patients With Recurrent/Refractory Pediatric Solid Tumors (Ewing's Sarcoma, Desmoplastic Small Round Cell Tumor, Osteosarcoma, Neuroblastoma, and Rhabdomyosarcoma) and Leukemia

Brief Summary

      This phase I trial is studying the side effects and best dose of tanespimycin in treating
      young patients with recurrent or refractory leukemia or selected solid tumors. Drugs used in
      chemotherapy, such as tanespimycin, work in different ways to stop cancer cells from dividing
      so they stop growing or die.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. Determine the dose-limiting toxicity and maximum tolerated dose (MTD) of
      17-N-allylamino-17-demethoxygeldanamycin (17-AAG) in pediatric patients with recurrent or
      refractory leukemia or selected solid tumors.

      II. Determine the levels of key proteins known to influence cancer cell survival and
      proliferation in patients treated with this drug at the MTD.

      SECONDARY OBJECTIVES:

      I. Determine the pharmacokinetics of this drug in these patients. II. Evaluate effects of
      genetic polymorphisms known to alter the activity of enzymes involved in the metabolism of
      this drug.

      III. Correlate the alteration of fludeoxyglucose F18 accumulation with tumor response in
      patients treated with this drug.

      OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
      diagnosis (leukemia vs solid tumor).

      Patients receive tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11 (for patients with
      solid tumors) OR days 1, 4, 8, 11, 15, and 18 (for patients with leukemia). Courses for all
      patients repeat every 21 days in the absence of disease progression or unacceptable toxicity.

      Cohorts of 3-6 patients receive escalating doses of tanespimycin 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. At least 15 patients are treated at the MTD.

      Patients are followed for 30 days.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

MTD, defined as the highest dose level with an observed incidence of DLT in no more than 1 out of 6 patients treated at a particular dose level

Secondary Outcome

 Change in Hsp90 client protein levels in relation to dose of tanespimycin

Condition

Childhood Chronic Myelogenous Leukemia

Intervention

tanespimycin

Study Arms / Comparison Groups

 Treatment (tanespimycin)
Description:  Patients receive tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11 (for patients with solid tumors) OR days 1, 4, 8, 11, 15, and 18 (for patients with leukemia). Courses for all patients repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tanespimycin until the 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. At least 15 patients are treated at the MTD.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

70

Start Date

September 2004


Primary Completion Date

August 2007

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of 1 of the following malignancies:

               -  Leukemia

                    -  Lymphoid, myeloid, or mixed lineage

                    -  Relapsed (in second or greater relapse) or refractory disease, confirmed by
                       1 of the following:

                         -  Bone marrow relapse, defined as either M3 bone marrow (> 25% blasts in
                            the bone marrow aspirate) OR M2 bone marrow (5-25% blasts in the bone
                            marrow aspirate) at any time after complete remission is attained

                         -  CNS relapse, defined as at least 5 WBC/mL by cytospin of any
                            cerebrospinal fluid (CSF) specimen OR less than 5 WBC/mL by cytospin of
                            2 consecutive CSF specimens obtained >= 4 weeks apart and having
                            definitive confirmation that blasts are derived from the original
                            leukemic clone by molecular cytogenetics, multiparameter flow
                            cytometry, or immunostaining of >= 2 antigens

                    -  Patients with underlying chronic myeloid leukemia must have > 25% blasts in
                       the bone marrow aspirate

                    -  Patients with M3 bone marrow AND extramedullary sites of disease, other than
                       leptomeningeal disease, are eligible

               -  Solid tumor

                    -  One of the following tumor types:

                         -  Neuroblastoma

                         -  Ewing's sarcoma

                         -  Osteosarcoma

                         -  Desmoplastic small round cell tumor

                         -  Rhabdomyosarcoma

                    -  Progressed after prior standard therapy OR no effective standard therapy
                       exists

                    -  Measurable or nonmeasurable disease

          -  No known brain metastases

          -  No active leptomeningeal leukemia, defined by the following criteria:

               -  WBC > 5/mm^3 in cerebrospinal fluid (CSF)

               -  Unequivocal confirmation of leukemic blasts in CSF by cell morphology

          -  No symptomatic CNS disease (e.g., cranial nerve abnormalities) without cytologic
             abnormality in CSF

          -  Performance status - Karnofsky 70-100% (for patients > 10 years of age)

          -  Performance status - Lansky 70-100% (for patients =< 10 years of age)

          -  More than 8 weeks

          -  Absolute neutrophil count >= 750/mm^3

          -  Platelet count >= 75,000/mm^3 (transfusion independent)

          -  Hemoglobin >= 8.5 g/dL (transfusion allowed)

          -  Bilirubin < 1.5 mg/dL

          -  ALT and AST =< 2.5 times upper limit of normal (ULN)

          -  INR =< 1.5 times ULN

          -  Albumin > 2.0 g/dL

          -  Creatinine =< 1.5 times ULN for age

          -  Creatinine clearance or radioisotope glomerular filtration rate > 60 mL/min

          -  Ejection fraction >= 50%

          -  Shortening fraction >= 28%

          -  QTc < 450 msec for men (470 msec for women)

               -  No congenital long QT syndrome

          -  LVEF > 40% by MUGA

          -  No symptomatic congestive heart failure

          -  No cardiac arrhythmia

          -  No New York Heart Association class III or IV heart failure

          -  No myocardial infarction within the past year

          -  No uncontrolled dysrhythmias

          -  No poorly controlled angina

          -  More than 12 months since active ischemic heart disease

          -  No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular
             fibrillation >= 3 beats in a row)

          -  No left bundle branch block

          -  No other significant cardiac disease

          -  No pulmonary fibrosis by radiography

          -  No ongoing or active bacterial or fungal infection

          -  No other uncontrolled illness

          -  No psychiatric illness or social situation that would preclude study compliance

          -  No history of serious allergic reaction attributed to eggs or dimethyl sulfoxide

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Recovered from all immunotherapy

          -  At least 6 months since prior allogeneic stem cell transplantation

          -  At least 3 months since prior autologous stem cell transplantation

          -  At least 2 weeks since prior biologic agents (e.g., monoclonal antibodies)

          -  At least 1 week since prior filgrastim (G-CSF) or sargramostim (GM-CSF)

          -  Recovered from all prior chemotherapy

          -  At least 2 weeks since prior chemotherapy (for patients with leukemia only)

          -  At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) (for
             patients with solid tumors)

          -  No prior oxaliplatin

          -  No concurrent corticosteroids except for the treatment of adrenal crises in patients
             with suppressed hypothalamic-pituitary-adrenal axis response OR for treatment of
             allergic reactions to medications or blood products

          -  Recovered from all prior radiotherapy

          -  At least 6 months since prior radiotherapy to >= 50% of the pelvis

          -  At least 6 months since prior radiotherapy to substantial bone marrow, including total
             body irradiation

          -  At least 4 weeks since prior local (small port) radiotherapy

          -  No prior radiotherapy to the heart

          -  At least 1 week since prior retinoids

          -  No concurrent antiretroviral therapy for HIV-positive patients

          -  No concurrent medication to control arrhythmias

          -  No concurrent medications that prolong or may prolong QTc interval

          -  No other concurrent investigational agents

          -  No other concurrent anticancer therapy
      

Gender

All

Ages

N/A - 21 Years

Accepts Healthy Volunteers

No

Contacts

Tanya Trippett, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00093821

Organization ID

NCI-2012-01456

Secondary IDs

04-069

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Tanya Trippett, Principal Investigator, Memorial Sloan Kettering Cancer Center


Verification Date

June 2013