Genetically Engineered Cells (NY-ESO-1 TCR Engineered T Cells and HSCs) After Melphalan Conditioning Regimen in Treating Patients With Recurrent or Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

NCT03691376 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: i 287616NCI-2018-01758
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the best dose and side effects of NY-ESO-1 T cell receptor (TCR) engineered T cells and how well they work with NY-ESO-1 TCR engineered hematopoietic stem cells (HSCs) after melphalan conditioning regimen in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent) or does not respond to treatment (refractory). The melphalan conditioning chemotherapy makes room in the patient's bone marrow for new blood cells and blood-forming cells (stem cells) to grow. Giving NY-ESO-1 TCR T cells and stem cells after the conditioning chemotherapy is intended to replace the immune system with new immune cells that have been redirected to attack and kill the cancer cells and thereby improve immune system function against cancer. Giving NY-ESO-1 TCR engineered T cells and HSCs after melphalan may work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

Conditions

Platinum-Resistant Fallopian Tube Carcinoma; Platinum-Resistant Ovarian Carcinoma; Platinum-Resistant Primary Peritoneal Carcinoma; Platinum-Sensitive Fallopian Tube Carcinoma; Platinum-Sensitive Ovarian Carcinoma; Platinum-Sensitive Primary Peritoneal Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Refractory Fallopian Tube Carcinoma; Refractory Ovarian Carcinoma; Refractory Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  The frequency of toxicities will be tabulated by grade across all dose levels and cycles.

  Up to 9 months post infusion

• Maximum tolerated dose (MTD)

  Dose limiting toxicities will be used in the estimation of the MTD and the accompanying of the dose escalation decisions. The frequency of toxicities will also be tabulated for the dose estimated to be the MTD.

  Up to 9 months post-infusion

Secondary Outcomes (8)

• Change in Immunological parameters associated with T cell persistence

  Baseline up to 15 years

• Tumor response rates to treatment

  Up to 15 years

• Progression-free survival

  From start of the treatment until the first occurrence of confirmed progression, assessed up to 15 years

• Overall survival

  From start of the treatment until death, assessed up to 15 years

• Duration of response

  Up to 15 years

Study Arms (1)

Treatment (autologous NY-ESO-1 engineered T and HSC)

EXPERIMENTAL

Patients receive melphalan IV over 30 minutes on day -1. Patients then receive autologous NY-ESO-1 CD4-TCR CD34+ HSC IV on day 0 and autologous NY-ESO-1-specific CD8-positive T lymphocytes IV between days 7 and 21. Patients also receive aldesleukin SC BID for 14 days on the following day after the T cell infusion (between days 8 and 22).

Biological: Aldesleukin; Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes; Other: Cellular Therapy; Drug: Melphalan

Interventions

Aldesleukin BIOLOGICAL

Given SC

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, recombinant human interleukin-2

Treatment (autologous NY-ESO-1 engineered T and HSC)

Autologous NY-ESO-1-specific CD8-positive T Lymphocytes BIOLOGICAL

Given IV

Treatment (autologous NY-ESO-1 engineered T and HSC)

Cellular Therapy OTHER

Given autologous NY-ESO-1 CD4-TCR CD34+ HSC IV

Also known as: Cell Therapy

Treatment (autologous NY-ESO-1 engineered T and HSC)

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine nitrogen mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (autologous NY-ESO-1 engineered T and HSC)

Eligibility Criteria

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

You may qualify if:

• Must have a diagnosis of platinum-sensitive or platinum-resistant recurrent or refractory epithelial ovarian, primary peritoneal or fallopian tube carcinoma and have progressed, relapsed, or recurred through at least one or more prior lines of standard-of-care therapies. For platinum sensitive patients, the standard of care therapies include additional platinum-containing regimens and bevacizumab
• Have been informed of other treatment options
• Must be HLA- A\*02.1 and HLA-DP\*04 positive. Retesting is not required for patients who have previous documented positivity
• Patient's tumor must be positive by histological or molecular assay for NY-ESO-1
• Have an Eastern Cooperative Oncology group (ECOG) performance status of 0 or 1
• Life expectancy of \> 4 months
• At least 4 weeks from prior chemotherapy, radiotherapy or immunotherapy, or prior investigational agents
• Must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Must have adequate venous access for apheresis (pheresis catheter placement for cell collection is allowed)
• Since the study drug may affect pregnancy since it targets proteins present during development, women of childbearing potential are requested to use acceptable methods of birth control for the duration of the study and until persistence of the study drug is no longer detected in the patient by polymerase chain reaction (PCR). This may be a period of several years. Methods for acceptable birth control include: condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception. It is recommended that a combination of two methods be used
• Leukocytes \>= 3 x 10\^9/L
• Absolute neutrophil count \>= 1.5 x 10\^9/L
• Platelets \>= 100 x 10\^9/L
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal

You may not qualify if:

• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in the study
• Prior malignancy (except non melanoma skin cancer) within 3 years
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
• Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g., interleukin 2, interferon alpha or gamma, granulocyte colony stimulating factors, etc.) within 30 days prior to study entry
• Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or cytomegalovirus (CMV) as defined below, due to the immunosuppressive effects of chemo-conditioning used and the unknown risks associated with viral replication
• Positive serology for HIV
• Active hepatitis B infection as determined by test for hepatitis B surface antigen (Ag)
• Active hepatitis C. Patients will be screened for HCV antibody. If the HCV antibody is positive, a screening HCV ribonucleic acid (RNA) by any reverse transcriptase (RT) PCR or branched deoxyribonucleic acid (bDNA) assay must be performed at screening by a local laboratory with a Clinical Laboratory Improvement Act (CLIA) certification or its equivalent. Eligibility will be determined based on a negative screening value. The test is not required if documentation of a negative result of a HCV RNA test performed within 60 days prior to screening is provided.
• Serology (CMV IgG) positive for active CMV
• Received any previous gene therapy using an integrating vector within 6 months
• Pregnancy or breast-feeding
• Lack of availability of a patient for immunological and clinical follow up assessment
• Evidence or history of significant cardiac disease (including myocardial infarction \[MI\] in the past 6 months, significant cardiac arrhythmia, stage III or IV congestive heart failure \[CHF\]). Cardiac stress test will be done if clinically indicated. (The specific test to be chosen at the discretion of the principal investigator \[PI\])
• Patients with pulmonary function test abnormalities as evidenced by a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) \< 70% of predicted for normality will be excluded

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

aldesleukin; Cell- and Tissue-Based Therapy; Melphalan

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

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Emese Zsiros, MD

  Roswell Park Cancer Institute

  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: September 27, 2018
• First Posted: October 1, 2018
• Study Start: March 8, 2019
• Primary Completion: January 30, 2021
• Study Completion: June 24, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

US (1)