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

3 december 2017 uppdaterad av: Masonic Cancer Center, University of Minnesota

MT2007-19R: WCC #53 Allogeneic Natural Killer Cells in Patients With Recurrent Ovarian Cancer, Fallopian Tube, and Primary Peritoneal Cancer

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.

Studieöversikt

Detaljerad beskrivning

OBJECTIVES:

Primary

  • To evaluate the in vivo expansion of an infused allogeneic natural killer (NK) cell product following a preparative regimen comprising cyclophosphamide, fludarabine phosphate, and total-body irradiation in treating patients with recurrent and/or metastatic ovarian, fallopian tube, or primary peritoneal 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 Response Evaluation Criteria in Solid Tumours (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 preceding natural killer (NK) cell infusion and cyclophosphamide IV on days 5 and 4 preceding NK cell infusion. Patients also undergo total-body irradiation on day 1 preceding NK cell infusion.
  • Allogeneic natural killer (NK) cell administration and aldesleukin: Patients receive aldesleukin-activated haploidentical allogeneic NK cells intravenously (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 post NK cell infusion 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.

Studietyp

Interventionell

Inskrivning (Faktisk)

14

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

    • Minnesota
      • Minneapolis, Minnesota, Förenta staterna, 55455
        • Masonic Cancer Center at University of Minnesota

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Kvinna

Beskrivning

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Icke-randomiserad
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Total Body Irradiation

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.

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.
Andra namn:
  • Zyloprim
60 mg/m^2 on Days 4 and 5 preceding natural killer cell infusion.
Andra namn:
  • Cytoxan
25 mg/m^2 on Days 6 through 2 preceding natural killer cell infusion.
Andra namn:
  • Fludarabin
200 cGy Day 1 preceding natural killer cell infusion.
Andra namn:
  • TBI
Given day 0 - dose of 1.5-8.0 * 10^7/kg
Andra namn:
  • related donor haploidentical allogenic cell infusion
10 MU 3 times/week for a total of 6 doses beginning Day 0
Andra namn:
  • IL-2
  • Interleukin-2
Experimentell: No Total Body Irradiation

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.

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.
Andra namn:
  • Zyloprim
60 mg/m^2 on Days 4 and 5 preceding natural killer cell infusion.
Andra namn:
  • Cytoxan
25 mg/m^2 on Days 6 through 2 preceding natural killer cell infusion.
Andra namn:
  • Fludarabin
Given day 0 - dose of 1.5-8.0 * 10^7/kg
Andra namn:
  • related donor haploidentical allogenic cell infusion
10 MU 3 times/week for a total of 6 doses beginning Day 0
Andra namn:
  • IL-2
  • Interleukin-2

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Number of Patients With In Vivo Expansion of Infused Allogeneic Natural Killer (NK) Cell Product
Tidsram: Day 12-14
Detection of an absolute donor derived cell count of > or = 100 cells/mL after NK cell infusion.
Day 12-14

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Number of Patients Per Disease Response
Tidsram: 1 Month After Natural Killer Cell Infusion (Day 30)
Response Evaluation Criteria in Solid Tumors (RECIST) criteria: Complete Response (CR)-Disappearance of all target lesions (TL); Partial Response (PR)-< or = 30% decrease in the sum of the longest diameter (LD) of TL, reference baseline sum LD; Stable Disease (SD)-Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference the smallest sum LD since the treatment started; Progressive Disease (PD)- < or = 20% increase in the sum of the LD of TL, reference the smallest sum LD recorded since treatment started or appearance of < or = 1 new lesion.
1 Month After Natural Killer Cell Infusion (Day 30)
Median Number of Days to Progression
Tidsram: From date of first treatment to disease progression
Median number of days from first date of treatment to date of disease progression (appearance of new metastatic lesions or objective tumor progression). Defined by computated tomography (CT) imaging based on Response Evaluation Criteria In Solid Tumors (RECIST): Progressive Disease (PD) > or = 20% increase in sum of all target or any new lesions.
From date of first treatment to disease progression
Median Overall Survival Number of Days Patients Alive After Treatment
Tidsram: From first date on-study (treatment) to date of death
Median number of days patients alive from date of treatment to date of death or date of last follow-up if censored.
From first date on-study (treatment) to date of death

Samarbetspartners och utredare

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Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 mars 2008

Primärt slutförande (Faktisk)

1 augusti 2009

Avslutad studie (Faktisk)

1 augusti 2009

Studieregistreringsdatum

Först inskickad

3 april 2008

Först inskickad som uppfyllde QC-kriterierna

3 april 2008

Första postat (Uppskatta)

4 april 2008

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

28 december 2017

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

3 december 2017

Senast verifierad

1 december 2017

Mer information

Termer relaterade till denna studie

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