Laboratory-Treated Donor Natural Killer Cells and Aldesleukin After Cyclophosphamide and Fludarabine in Treating Patients With Recurrent and/or Metastatic Ovarian Cancer - Full Text View

Sponsors and Collaborators:	Masonic Cancer Center, University of Minnesota National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00652899

Purpose

RATIONALE: Giving chemotherapy, such as cyclophosphamide and fludarabine, before a donor natural killer cell infusion helps stop the growth of tumor cells. It also helps stop the patient's immune system from rejecting the donor's natural killer cells. Aldesleukin may stimulate the natural killer cells to kill ovarian cancer cells. Treating the donor natural killer cells with aldesleukin may help the natural killer cells kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving laboratory-treated donor natural killer cells together with aldesleukin works when given after cyclophosphamide and fludarabine in treating patients with recurrent and/or metastatic ovarian cancer.

Condition	Intervention	Phase
Ovarian Cancer	Drug: aldesleukin Drug: cyclophosphamide Drug: fludarabine phosphate Drug: lymphokine-activated killer cells Drug: therapeutic allogeneic lymphocytes	Phase II

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate Aldesleukin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Allogeneic Natural Killer Cells in Patients With Recurrent Ovarian Cancer

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

Primary Outcome Measures:

In vivo expansion of an infused allogeneic natural killer cell product [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety and toxicity [ Designated as safety issue: Yes ]
Disease response (complete or partial response) or clinical benefit (stable disease for > 6 months) as measured by RECIST criteria [ Designated as safety issue: No ]
Time to progression [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Association between clinical response and donor/recipient KIR ligand matching status [ Designated as safety issue: No ]

Estimated Enrollment:	14
Study Start Date:	March 2008
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To evaluate the in vivo expansion of an infused allogeneic natural killer (NK) cell product following a preparative regimen comprising cyclophosphamide and fludarabine phosphate in treating patients with recurrent and/or metastatic ovarian cancer.

Secondary

To characterize the quantitative and qualitative toxicities of this treatment regimen.
To estimate disease response (complete or partial response) or clinical benefit (stable disease for > 6 months) as measured by RECIST criteria.
To estimate time to progression and overall survival.
To estimate the association between clinical response and donor/recipient KIR ligand matching status.

Tertiary

To evaluate immune activation of the in vivo expanded haploidentical allogeneic NK cells and its effect on the immune system.

OUTLINE:

Preparative regimen: Patients receive fludarabine phosphate IV on days -6 to -2 and cyclophosphamide IV on days -5 and -4.
Allogeneic natural killer (NK) cell administration and aldesleukin: Patients receive aldesleukin-activated haploidentical allogeneic NK cells IV on day 0. Beginning 4-6 hours after allogeneic NK cell infusion, patients receive aldesleukin subcutaneously (SC) 3 times a week for 6 doses.

Patients achieving any initial response (complete or partial response) or a clinical benefit (stable disease for > 6 months) who progress after 6 months may receive 1 re-treatment course as above.

Blood samples are collected at baseline, on days 0, 7, 14, and 28, and then at 2 and 3 months for cytokine measurements, immunophenotyping, functional analyses, and testing for persistence of donor cells.

After completion of study treatment, patients are followed periodically for at least 1 year.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of ovarian cancer
- Recurrent and/or metastatic disease
Measurable disease, defined as ≥ 1.0 cm by RECIST criteria
Disease progression during or failed to respond to ≥ 2 prior salvage chemotherapy regimens for recurrent and/or metastatic ovarian cancer
History of brain metastases allowed provided they have been stable for ≥ 3 months after treatment
- A brain CT scan is required for patients with known brain metastases or with new clinical signs or symptoms of brain metastases at time of study enrollment
No bone-only metastatic disease
Related HLA-haploidentical natural killer cell donor available (by at least class I serologic typing)

PATIENT CHARACTERISTICS:

GOG performance status 0-1
ANC ≥ 1,000 x 10^9/L
Platelet count ≥ 80,000 x 10^9/L
Hemoglobin ≥ 9 g/dL
Creatinine ≤ 2.0 mg/dL
Bilirubin ≤ 3.0 mg/dL
AST and ALT < 5 times upper limit of normal (ULN)
Alkaline phosphatase < 5 times ULN
LVEF > 40% (testing required only if symptomatic or prior known impairment)
Corrected DLCO and FEV_1 > 50% (testing required only if symptomatic or prior known impairment)
No active infection
- Must be afebrile, off antibiotics, and have no uninvestigated radiologic lesions (infiltrates or lesions with negative cultures or biopsies after clinically appropriate testing are allowed)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 3 days since prior prednisone or other immunosuppressive medications

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00652899

Locations

United States, Minnesota
Masonic Cancer Center at University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office - Masonic Cancer Center at University o 612-624-2620

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Melissa A. Geller, MD

Masonic Cancer Center, University of Minnesota

More Information

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

Responsible Party:	Masonic Cancer Center at University of Minnesota ( Melissa A. Geller )
Study ID Numbers:	CDR0000592732, UMN-2007LS138, UMN-MT2007-19R, UMN-WCC-53, UMN-0712M23462
Study First Received:	April 3, 2008
Last Updated:	December 16, 2008
ClinicalTrials.gov Identifier:	NCT00652899
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent ovarian epithelial cancer
recurrent ovarian germ cell tumor
stage IV ovarian epithelial cancer
stage IV ovarian germ cell tumor

Study placed in the following topic categories:

Ovarian cancer
Ovarian Neoplasms
Gonadal Disorders
Genital Neoplasms, Female
Endocrine System Diseases
Urogenital Neoplasms
Fludarabine monophosphate
Cyclophosphamide

Ovarian Diseases
Ovarian epithelial cancer
Recurrence
Genital Diseases, Female
Aldesleukin
Fludarabine
Endocrinopathy
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Anti-HIV Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Antiviral Agents
Immunosuppressive Agents

Pharmacologic Actions
Adnexal Diseases
Neoplasms
Neoplasms by Site
Anti-Retroviral Agents
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009