Allogeneic Natural Killer Cells in Patients With Recurrent Ovarian Cancer, Fallopian Tube, and Primary Peritoneal Cancer

NCT00652899 | Terminated Phase 2 Results DMC

• 4 other identifiers: 2007LS138UMN-MT2007-19RUMN-WCC-53UMN-0712M23462
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Giving chemotherapy, such as cyclophosphamide and fludarabine, and total-body irradiation 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, fallopian tube, or primary peritoneal 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, fludarabine, and total-body irradiation in treating patients with recurrent and/or metastatic ovarian, fallopian tube, or primary peritoneal cancer.

Conditions

Fallopian Tube Cancer; Ovarian Cancer; Peritoneal Cavity Cancer

Keywords

recurrent ovarian epithelial cancer; recurrent ovarian germ cell tumor; stage IV ovarian epithelial cancer; stage IV ovarian germ cell tumor; fallopian tube cancer; peritoneal cavity cancer

Outcome Measures

Primary Outcomes (1)

• Number of Patients With In Vivo Expansion of Infused Allogeneic Natural Killer (NK) Cell Product

  Detection of an absolute donor derived cell count of \> or = 100 cells/mL after NK cell infusion.

  Day 12-14

Secondary Outcomes (3)

• Number of Patients Per Disease Response

  1 Month After Natural Killer Cell Infusion (Day 30)

• Median Number of Days to Progression

  From date of first treatment to disease progression

• Median Overall Survival Number of Days Patients Alive After Treatment

  From first date on-study (treatment) to date of death

Study Arms (2)

Total Body Irradiation

EXPERIMENTAL

This group includes patients that received all chemotherapy, infusion of natural killer (NK) cells and total body irradiation per protocol. 1\. Allopurinol 300 mg by mouth daily (unless known allergy) before beginning chemotherapy and continuing through day 14 post NK cell infusion. 2. Cyclophosphamide 60 mg/m\^2 on Days 4 and 5 preceding NK cell infusion. 3. Fludarabine phosphate 25 mg/m\^2 on Days 6 through 2 preceding NK cell infusion. 4. Radiation: total-body irradiation 200 cGy Day 1 preceding NK cell infusion. 5. Allogeneic natural killer cells- Given day 0 - dose of 1.5-8.0 \* 10\^7/kg. 6. Aldesleukin 10 million units 3 times/week for a total of 6 doses beginning Day 0.

Biological: Allopurinol; Drug: Cyclophosphamide; Drug: Fludarabine phosphate; Radiation: total-body irradiation; Biological: Allogeneic natural killer cells; Biological: Aldesleukin

No Total Body Irradiation

EXPERIMENTAL

This group includes patients that received chemotherapy and infusion of natural killer cells, but did not receive total body irradiation. 1\. Allopurinol 300 mg by mouth daily (unless known allergy) before beginning chemotherapy and continuing through day 14 post NK cell infusion. 2. Cyclophosphamide 60 mg/m\^2 on Days 4 and 5 preceding NK cell infusion. 3. Fludarabine phosphate 25 mg/m\^2 on Days 6 through 2 preceding NK cell infusion. 4. Allogeneic natural killer cells- Given day 0 - dose of 1.5-8.0 \* 10\^7/kg. 5. Aldesleukin 10 million units 3 times/week for a total of 6 doses beginning Day 0.

Biological: Allopurinol; Drug: Cyclophosphamide; Drug: Fludarabine phosphate; Biological: Allogeneic natural killer cells; Biological: Aldesleukin

Interventions

Allopurinol BIOLOGICAL

All patients are to receive allopurinol 300 mg PO daily (unless known allergy) before beginning chemotherapy and continuing through day 14 post natural killer cell infusion.

Also known as: Zyloprim

No Total Body Irradiation; Total Body Irradiation

Cyclophosphamide DRUG

60 mg/m\^2 on Days 4 and 5 preceding natural killer cell infusion.

Also known as: Cytoxan

No Total Body Irradiation; Total Body Irradiation

Fludarabine phosphate DRUG

25 mg/m\^2 on Days 6 through 2 preceding natural killer cell infusion.

Also known as: Fludarabine

No Total Body Irradiation; Total Body Irradiation

total-body irradiation RADIATION

200 cGy Day 1 preceding natural killer cell infusion.

Also known as: TBI

Total Body Irradiation

Allogeneic natural killer cells BIOLOGICAL

Given day 0 - dose of 1.5-8.0 \* 10\^7/kg

Also known as: related donor haploidentical allogenic cell infusion

No Total Body Irradiation; Total Body Irradiation

Aldesleukin BIOLOGICAL

10 MU 3 times/week for a total of 6 doses beginning Day 0

Also known as: IL-2, Interleukin-2

No Total Body Irradiation; Total Body Irradiation

Eligibility Criteria

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

You may qualify if:

• Diagnosis of recurrent ovarian cancer, fallopian tube, or primary peritoneal cancer who meets the following criteria:
• Measurable disease (≥ 1 cm) per Response Evaluation Criteria for Solid Tumors (RECIST) - patients with bone as their only site of metastatic disease will not be eligible
• Progression on or failure to respond to at least 2 salvage chemotherapy regimens (2 regimens given for disease recurrence) for recurrent/metastatic ovarian, fallopian tube, or primary peritoneal cancer
• If history of brain metastases, stable for at least 3 months after treatment - A brain computed tomography (CT) scan will only be required in subjects with known brain metastases at the time of enrollment or in subjects with new clinical signs or symptoms suggestive of brain metastases.
• Available related HLA-haploidentical natural killer (NK) cell donor (by at least class I serologic typing). If biologic parents or siblings are available, can proceed with work-up of subject prior to return of human leukocyte antigen (HLA) typing results.
• Age 18 years or older
• Gynecology Oncology Group (GOG) performance status 0 or 1
• Adequate organ function as determined by the following criteria within 14 days of study enrollment:
• Bone marrow: platelets ≥ 80,000 x 10\^9/L and hemoglobin ≥ 9g/dL, unsupported by transfusions; absolute neutrophil count (ANC) ≥ 1000 x 10\^9/L, unsupported by granulocyte-colony stimulating factor (G-CSF) or granulocyte macrophage-colony stimulating factor (GM-CSF)
• Renal function: creatinine (Cr) ≤ 2.0 mg/dL
• Liver function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, alkaline phosphatase \< 5 times upper limit of institutional normal
• Cardiac: Left ventricular ejection fraction \>40%
• Pulmonary function: \> 50% corrected Carbon Monoxide Diffusing Capacity (DLCO) and Forced expiratory volume in one second (FEV1), if presence of pleural effusion due to metastatic disease \>40% corrected DLCO and FEV1 acceptable.
• Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to Day 0
• Voluntary written informed consent signed before performance of any study related procedure not part of normal medical care.

You may not qualify if:

• Pregnant or lactating - The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
• Active infection - subjects must be afebrile, off antibiotics, and with no uninvestigated radiologic lesions (infiltrates or lesions with negative cultures or biopsies are allowed).
• Human anti-mouse antibody (HAMA) monitoring: All subjects will be questioned about prior exposure to antibody therapy (including OKT3, Rituximab, Trastuzumab, etc). Responses will be recorded and reported to the FDA as part of the annual report. For subjects with no prior antibody therapy exposure, no further action will be taken. For subjects who have received previous antibody therapies 10 ml of serum (red top tube) will be drawn before starting therapy and banked per section 8.1. The presence of HAMA will not exclude a patient from the study.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

Allopurinol; Cyclophosphamide; fludarabine phosphate; fludarabine; Whole-Body Irradiation; aldesleukin; Interleukin-2

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)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Limitations and Caveats

Endpoint for association of clinical benefit response with donor/recipient KIR ligand matching status is not evaluable due to 0 complete responders. Correlative laboratory objectives are irrelevant due to ineffectiveness of study regimen.

Results Point of Contact

• Title: Melissa Geller, M.D.
• Organization: University of Minnesota, Dept. Ob/Gyn

gelle005@umn.edu

612-626-3111

Study Officials

• Melissa A. Geller, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2008
• First Posted: April 4, 2008
• Study Start: March 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: December 28, 2017
• Results First Posted: September 15, 2010

Record last verified: 2017-12

Locations

US (1)