NCT01477021

Brief Summary

This phase I trial studies the side effects and how well giving autologous T cells with cyclophosphamide works in treating patients with soft tissue sarcoma that is metastatic or cannot be removed by surgery. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving autologous T cells together with cyclophosphamide may kill more tumor cells.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 17, 2011

Completed
5 days until next milestone

First Posted

Study publicly available on registry

November 22, 2011

Completed
1 month until next milestone

Study Start

First participant enrolled

January 1, 2012

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2013

Completed
Last Updated

December 11, 2014

Status Verified

December 1, 2014

Enrollment Period

1.7 years

First QC Date

November 17, 2011

Last Update Submit

December 9, 2014

Conditions

Adult LiposarcomaAdult Synovial SarcomaRecurrent Adult Soft Tissue SarcomaStage III Adult Soft Tissue SarcomaStage IV Adult Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

  • Incidence of treatment-related toxicity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    Patients will be monitored for treatment-related toxicities. All unexpected grade 3, 4, and 5 toxicities will be reported descriptively.

    Up to 10 weeks

Secondary Outcomes (1)

  • Antitumor efficacy as determined by CT scan

    After week 8

Study Arms (1)

Treatment (NY-ESO-1 specific CD8+ T cells)

EXPERIMENTAL

Patients receive cyclophosphamide IV on days -3 and -2. Patients receive NY-ESO-1-specific T cells IV on day 0.

Drug: cyclophosphamideBiological: NY-ESO-1-specific T cellsOther: laboratory biomarker analysis

Interventions

cyclophosphamideDRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Treatment (NY-ESO-1 specific CD8+ T cells)
NY-ESO-1-specific T cellsBIOLOGICAL

Given IV

Treatment (NY-ESO-1 specific CD8+ T cells)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (NY-ESO-1 specific CD8+ T cells)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histopathological documentation of the diagnosis of synovial sarcoma or myxoid liposarcoma with metastatic or unresectable disease who have received an alkylating agent containing regimen (such as doxorubicin plus ifosphamide); this includes patients who received an alkylating agent as part of adjuvant therapy and then relapsed; patients who were treated on the PICCASSO trial who have progressed will be allowed on the study; "unresectable disease" shall include patients with locally advanced disease where a surgery could be attempted but where this surgery would be mutilating, debilitating and would likely fail to result in long-term disease free survival; in this setting a patient might reasonably choose to undergo salvage/second line systemic therapy but could also pursue aggressive surgical options as standard of care
  • Able to tolerate high-dose cyclophosphamide
  • NY-ESO-1 expression in \> 25% of tumor by immunohistochemistry (IHC) (at least 2+)
  • Expression of human leukocyte antigen (HLA)-A0201; high resolution HLA typing performed at any experienced HLA lab will be accepted
  • Zubrod performance status of '0-1'
  • Patients with metastatic disease must have bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (computed tomography \[CT\] scan)
  • All patients must have an electrocardiogram (ECG); all patients must have a normal stress test within 182 days prior to treatment
  • Patients must have already been leukapheresed on either protocol 1246 or 2365 prior to entry into this study; patients who are unable to have a leukapheresis product collected, for whatever reason, will be unable to participate in this study
  • If there is a patient with an NY-ESO-1 expressing sarcoma who would be otherwise eligible for the trial, where there has been disagreement between pathologists regarding the histopathologic diagnosis, eligibility will be decided on by the principal investigator (PI)
  • Patients must have had NY-ESO-1 specific cells already in production; patients must have NY-ESO-1 specific cells that have been generated and sorted; these cells may be either in the process of expansion or expanded and frozen at the time of enrollment
  • Patients with definitively treated brain metastasis and patients with 4 or fewer untreated lesions less than 1 cm each will be included at the discretion of the principal investigator (PI)
  • Patients must be off metformin at least 2 weeks before receiving T cell therapy
  • Patients must have hemoglobin A1C \< 8.5%

You may not qualify if:

  • Patients for whom we are unable to generate NY-ESO-1 specific cells
  • Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to entry
  • Serum creatinine \> 1.5 mg/dL or glomerular filtration rate \< 50
  • Significant hepatic dysfunction (serum glutamic oxaloacetic transaminase \[SGOT\] \> 150 IU or \> 3x upper limit of normal \[ULN\])
  • Bilirubin \> 1.6 mg/dL
  • Prothrombin time (PT) \> 1.5 x control
  • Most patients with metastatic sarcoma will have pulmonary metastasis and it is expected that the majority will have some mild to moderate baseline shortness of breath; these patients will be allowed on study so long as their Eastern Cooperative Oncology Group (ECOG) performance status is 1; patients with severe pulmonary dysfunction (\>= grade 3 respiratory disorders as defined by Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]4) will not allowed on study until their condition improves; however, patients who have recently experienced a decrease in their pulmonary function will be required to undergo pulmonary function testing; patients with a forced expiratory volume in one second (FEV1) \< 1.5L or diffusing capacity of carbon monoxide (DLco) (corrected \[corr\] for hemoglobin \[Hgb\]) \< 50% will be excluded; patients with a reversible cause of pulmonary dysfunction may undergo repeat testing and enroll if their pulmonary function tests (PFT's) meet criterion
  • All patients must have an echocardiogram (echo) showing ejection fraction (EF) \> 50% and normal troponin and creatine kinase (CK) MB (echo may be done at the time of stress test as a stress echo); furthermore the following significant cardiovascular abnormalities will be excluded:
  • Active, symptomatic congestive heart failure
  • Clinically significant hypotension
  • Symptoms of coronary artery disease
  • Presence of cardiac arrhythmias on EKG requiring drug therapy which has not been stable for at least 6 months
  • Patients with symptomatic untreated brain metastasis or asymptomatic untreated brain metastasis \> 1 cm will not be allowed to participate; additionally, patients with five or more untreated brain metastasis under 1 cm will not be allowed to participate; treatment may include surgery or stereotactic radiation at the discretion of the patient's treatment team; patients must be off steroids when starting therapy
  • Patients with active infections or oral temperature \> 38.2 C within 72 hours of study entry or systemic infection requiring chronic maintenance or suppressive therapy
  • Chemotherapeutic agents (standard or experimental or other immunosuppressive therapies) less than 3 weeks prior to T cell therapy; (patients with bulky disease may undergo cytoreductive chemotherapy but treatment will be discontinued at least 3 weeks prior to T cell infusion); patients may receive palliative radiation therapy two weeks prior to T cell infusion
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

LiposarcomaSarcoma, SynovialSarcoma

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Adipose TissueNeoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsNeoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Seth Pollack

    Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 17, 2011

First Posted

November 22, 2011

Study Start

January 1, 2012

Primary Completion

September 1, 2013

Last Updated

December 11, 2014

Record last verified: 2014-12

Locations

US(1)