Expired Study
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New York, New York 10065


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. (fludarabine treatment closed as of 12/012009)


Study summary:

OBJECTIVES: - To assess the safety and tolerability of in vitro expanded autologous WT1 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 maximum tolerated dose of autologous WT1 specific T cells in these patients. - To quantitate alterations in the concentration of WT1 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 ( fludarabine treatment closed as of 12/01/2009): 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 II and III also undergo pre-infusion lymphodepletive conditioning comprising cyclophosphamide IV on day -2 and fludarabine phosphate IV over approximately 30 minutes on days -6 to -2. After a 48-hour rest period, patients receive autologous WT1-specific T cells. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease after completion of therapy, may receive additional courses of autologous WT1-specific T cells every 14 days. 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.


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 ≤ 1.5 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


Study is Available At:


Original ID:

06-155


NCT ID:

NCT00562640


Secondary ID:

MSKCC-06155


Study Acronym:


Brief Title:

Autologous T Cells With or Without Cyclophosphamide and Fludarabine in Treating Patients With Recurrent or Persistent Advanced Ovarian Epithelial Canc


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


Overall Status:

Active, not recruiting


Study Phase:

Phase 1


Genders:

Female


Minimum Age:

18 Years


Maximum Age:

120 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Memorial Sloan Kettering Cancer Center


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

21


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Roisin O'Cearbhaill, MB, BCh
Principal Investigator
Memorial Sloan Kettering Cancer Center

Study Dates

Start Date:October 2007
Completion Date:December 2018
Completion Type:Anticipated
Primary Completion Date:December 2018
Primary Completion Type:Anticipated
Verification Date:November 2017
Last Changed Date:November 6, 2017
First Received Date:November 21, 2007

Study Outcomes

Outcome Type:Primary Outcome
Measure:Safety and tolerability as assessed by NCI CTCAE v3.0
Time Frame:2 years
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Mean tolerated dose of autologous WT1 peptide-specific T cells
Time Frame:2 years
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Quantitation of alterations in the concentration of peptide-specific T cells in the blood at defined intervals post infusion
Time Frame:2 years
Safety Issues:False
Outcome Type:Primary Outcome
Measure: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
Time Frame:2 years
Safety Issues:False

Study Interventions

Intervention Type:Biological
Name:filgrastim
Description: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.
Arm Name:WT1-Specific T Cells
Intervention Type:Biological
Name:therapeutic autologous lymphocytes
Description:Autologous T-cell infusion with or without conditioning chemotherapy ( fludarabine treatment closed as of 12/01/2009): 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 II and III also undergo pre-infusion lymphodepletive conditioning comprising cyclophosphamide IV on day -2 and fludarabine phosphate IV over approximately 30 minutes on days -6 to -2. After a 48-hour rest
Arm Name:WT1-Specific T Cells
Intervention Type:Drug
Name:cyclophosphamide
Description:Patients enrolled in dose levels II and III also undergo pre-infusion lymphodepletive conditioning comprising cyclophosphamide IV on day -2
Arm Name:WT1-Specific T Cells
Intervention Type:Other
Name:laboratory biomarker analysis
Description:Obtained prior to adoptive therapy to quantitate baseline levels of WT1 reactive T cells, by quantitation of WT1 specific CTLp by LDA, T cells secreting IFNγ in response to peptide and, in HLA A0201+ patients, T cell binding WT1 peptide HLA A2 tetramers.
Arm Name:WT1-Specific T Cells
Other Name:After completion of study therapy, patients are fo

Study Arms

Study Arm Type:Experimental
Arm Name:WT1-Specific T Cells
Description:This is a phase I dose escalating trial designed to identify tolerable, clinically active doses of Wilms' tumor gene (WT1) peptide sensitized T cells when administered alone or with nonmyelosuppressive chemotherapy in patients with recurrent or persistent, evaluable WT1+ ovarian, primary peritoneal, or fallopian tube carcinomas.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Memorial Sloan Kettering Cancer Center
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: October 09, 2019

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