Autologous T Cells With or Without Cyclophosphamide and Fludarabine in Treating Patients With Recurrent or Persistent Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer - Full Text View

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00562640

Purpose

RATIONALE: Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected. Treating stem cells collected from the patient's blood in the laboratory may increase the number of immune cells that can mount an immune response against the tumor. The treated stem cells may help destroy any remaining tumor cells (graft-versus-tumor effect). Chemotherapy may also be given to the patient to prepare the bone marrow for the stem cell transplant.

PURPOSE: This phase I trial is studying the side effects and best dose of autologous T cells when given with or without cyclophosphamide and fludarabine in treating patients with recurrent or persistent advanced ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian tube cancer.

Condition	Intervention	Phase
Fallopian Tube Cancer Ovarian Cancer Peritoneal Cavity Cancer	Biological: filgrastim Biological: therapeutic autologous lymphocytes Drug: cyclophosphamide Drug: fludarabine phosphate Other: laboratory biomarker analysis	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
Official Title:	A Phase I Dose Escalation Safety and Feasibility Study of WT1-Specific T Cells for the Treatment of Patients With Advanced Ovarian, Primary Peritoneal, and Fallopian Tube Carcinomas

Resource links provided by NLM:

MedlinePlus related topics: Cancer Ovarian Cancer Wilms' Tumor

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate Filgrastim

U.S. FDA Resources

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

Primary Outcome Measures:

Safety and tolerability as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Mean tolerated dose of autologous WT1 peptide-specific T cells [ Designated as safety issue: No ]
Quantitation of alterations in the concentration of peptide-specific T cells in the blood at defined intervals post infusion [ Designated as safety issue: No ]
Effects of the adoptively transferred T cells on the growth and progression of advanced ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian tube cancer [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	October 2007
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

To assess the safety and tolerability of a single dose of in vitro expanded autologous WT1 peptide-specific T cells, when administered alone or in combination with non-myeloablative, immunosuppressive conditioning, in patients with recurrent or persistent, advanced, WT1-positive, ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian tube cancer.
To determine the mean tolerated dose of autologous WT1 peptide-specific T cells in these patients.
To quantitate alterations in the concentration of peptide-specific T cells in the blood at defined intervals post infusion with or without non-myeloablative, immunosuppressive conditioning in order to gain estimates regarding their survival and proliferation.
To assess the effects of the adoptively transferred T cells on the growth and progression of advanced ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian tube cancer.

OUTLINE: This is a dose-escalation study of WT1 peptide-specific T cells.

T-cell generation and isolation: Patients undergo collection of peripheral blood stem cells (PBMC) from which T cells are purified, stimulated in vitro with WT1 peptide-pulsed autologous EBV BLCL, and expanded ex vivo.
Stem cell mobilization and harvest: Patients receive filgrastim (G-CSF) subcutaneously daily for five days.

PBMC are collected by leukapheresis on the fifth day and then cryopreserved for subsequent reinfusion into the patient, in the event of prolonged cytopenia.

Autologous T-cell infusion with or without conditioning chemotherapy: Approximately 4-6 weeks after T-cell sensitization, patients receive an infusion of autologous WT1-specific T cells over 5-10 minutes on day 0.

Patients enrolled in dose levels IV and V also undergo pre-infusion lymphoablative conditioning comprising cyclophosphamide IV on days -6 to -5 and fludarabine phosphate IV over approximately 30 minutes on days -6 to -2.

After a 24-hour rest period, patients receive autologous WT1-specific T cells. Blood samples are obtained at baseline and periodically during study and assayed for alterations in circulating levels of WT1 peptide-specific T cells, for biochemical indices of tumor burden, and for radiologic evidence of tumor response. Serum CA125 levels are measured and the number of T cells generating interferon gamma in response to autologous EBV BLCL is quantitated.

After completion of study therapy, patients are followed for up to 12 weeks.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Pathologically confirmed ovarian epithelial carcinoma, primary peritoneal cavity carcinoma, or fallopian tube carcinoma
- Recurrent or persistent disease after treatment with platinum-based chemotherapy
  - Must have platinum-resistant or intolerant disease
Evaluable disease, as demonstrated by serological (i.e., CA 125), radiological, or pathological studies
Tumor must express the Wilms Tumor Gene 1 (WT1) peptide, as detected by IHC analysis of banked (i.e., paraffin-embedded) or freshly biopsied tumor nodules
- Only WT1 tumors graded as moderate to strong (scores 4-12) according to adapted German Immunoreactive Score criteria are considered positive
No prior or concurrent brain metastases

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 70-100% OR WHO PS 0-1
Life expectancy ≥ 6 months
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60mL/min
ALT and AST ≤ 2.5 times upper limit of normal (ULN)
Total bilirubin ≤ 2.5 times ULN
Adequate pulmonary and cardiac function
No clinical evidence of cardiopulmonary disease, which, in the opinion of the investigator, would preclude enrollment
Able to keep scheduled visits
No known hepatitis B or C infection
No known HIV positivity
No evidence of bowel obstruction
No clinically significant heart disease (New York Heart Association class III or IV)
No active infections requiring antibiotics within two weeks of study entry
No serious intercurrent illness requiring hospitalization
No history of primary or secondary immunodeficiency or autoimmune disease
No other cancers except nonmelanomatous skin cancer within the past 5 years
Not pregnant or lactating
No other issue which, in the opinion of the treating physician, would make the patient ineligible for the study

PRIOR CONCURRENT THERAPY:

More than 3 weeks since prior anticancer therapy (i.e., chemotherapy, biologic therapy, or immunotherapy)
No history of whole abdominal radiation therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00562640

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Carol Aghajanian, MD 212-639-2252 aghajanC@mskcc.org

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Carol Aghajanian, MD	Memorial Sloan-Kettering Cancer Center
Principal Investigator:	Richard J. O'Reilly, MD	Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000574375, MSKCC-06155
Study First Received:	November 21, 2007
Last Updated:	July 7, 2009
ClinicalTrials.gov Identifier:	NCT00562640 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
peritoneal cavity cancer
fallopian tube cancer

Study placed in the following topic categories:

Antimetabolites
Fallopian Tube Cancer
Immunologic Factors
Gonadal Disorders
Urogenital Neoplasms
Ovarian Diseases
Cyclophosphamide
Genital Diseases, Female
Wilms' Tumor
Peritoneal Diseases
Wilms Tumor
Ovarian Cancer
Alkylating Agents
Endocrine Gland Neoplasms
Ovarian Neoplasms

Digestive System Neoplasms
Genital Neoplasms, Female
Endocrine System Diseases
Fludarabine monophosphate
Abdominal Neoplasms
Ovarian Epithelial Cancer
Immunosuppressive Agents
Recurrence
Fallopian Tube Neoplasms
Carcinoma
Digestive System Diseases
Gastrointestinal Neoplasms
Antineoplastic Agents, Alkylating
Fludarabine
Peritoneal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Gonadal Disorders
Physiological Effects of Drugs
Urogenital Neoplasms
Ovarian Diseases
Cyclophosphamide
Genital Diseases, Female
Neoplasms by Site
Therapeutic Uses
Peritoneal Diseases
Alkylating Agents

Endocrine Gland Neoplasms
Ovarian Neoplasms
Digestive System Neoplasms
Genital Neoplasms, Female
Endocrine System Diseases
Fludarabine monophosphate
Abdominal Neoplasms
Immunosuppressive Agents
Fallopian Tube Neoplasms
Pharmacologic Actions
Adnexal Diseases
Fallopian Tube Diseases
Neoplasms
Digestive System Diseases
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 10, 2009