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 (Fludarabine Treatment Closed as of 12/01/2009)

NCT00562640 | Completed Phase 1 Results

• 2 other identifiers: 06-155MSKCC-06155
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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)

Conditions

Fallopian Tube Cancer; Ovarian Cancer; Primary Peritoneal Cavity Cancer

Keywords

recurrent ovarian epithelial cancer; stage IV ovarian epithelial cancer; recurrent primary peritoneal cavity cancer; stage IIIA primary peritoneal cavity cancer; stage IIIB primary peritoneal cavity cancer; stage IIIC primary peritoneal cavity cancer; stage IV primary peritoneal cavity cancer; recurrent fallopian tube cancer; stage IIIA fallopian tube cancer; stage IIIB fallopian tube cancer; stage IIIC fallopian tube cancer; stage IV fallopian tube cancer; stage IIIA ovarian epithelial cancer; stage IIIB ovarian epithelial cancer; stage IIIC ovarian epithelial cancer; 06-155

Outcome Measures

Primary Outcomes (4)

• Number of Participants Assessed for Safety and Tolerability as Assessed by NCI CTCAE v3.0

  Participant toxicity will be evaluated by using NCI CTCAE v3.0

  2 years

• Total Number of Dose Limiting Toxicities/DLT's

  2 years

• Mean Overall Survival

  Up to 3 years

• Best Response

  1 year

Study Arms (1)

WT1-Specific T Cells

EXPERIMENTAL

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.

Biological: filgrastim; Biological: therapeutic autologous lymphocytes; Drug: cyclophosphamide; Other: laboratory biomarker analysis

Interventions

filgrastim BIOLOGICAL

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.

WT1-Specific T Cells

therapeutic autologous lymphocytes BIOLOGICAL

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.

WT1-Specific T Cells

cyclophosphamide DRUG

Patients enrolled in dose levels II and III also undergo pre-infusion lymphodepletive conditioning comprising cyclophosphamide IV on day -2

WT1-Specific T Cells

laboratory biomarker analysis OTHER

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.

Also known as: After completion of study therapy, patients are followed for up to 12 weeks.

WT1-Specific T Cells

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Kyi C, Doubrovina E, Zhou Q, Kravetz S, Iasonos A, Aghajanian C, Sabbatini P, Spriggs D, O'Reilly RJ, O'Cearbhaill RE. Phase I dose escalation safety and feasibility study of autologous WT1-sensitized T cells for the treatment of patients with recurrent ovarian cancer. J Immunother Cancer. 2021 Aug;9(8):e002752. doi: 10.1136/jitc-2021-002752.

  PMID: 34433633 DERIVED

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

Filgrastim; Cyclophosphamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Roisin O'Cearbhaill, MD
• Organization: Memorial Sloan Kettering Cancer Center

ocearbhr@mskcc.org

646-888-4227

Study Officials

• Roisin O'Cearbhaill, MB, BCh

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Richard J. O'Reilly, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2007
• First Posted: November 22, 2007
• Study Start: October 16, 2007
• Primary Completion: August 3, 2021
• Study Completion: August 3, 2021
• Last Updated: September 15, 2023
• Results First Posted: September 15, 2023

Record last verified: 2021-08

Locations

US (1)