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

3 december 2017 bijgewerkt door: 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.

Studie Overzicht

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

14

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

    • Minnesota
      • Minneapolis, Minnesota, Verenigde Staten, 55455
        • Masonic Cancer Center at University of Minnesota

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Vrouw

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Andere namen:
  • Zyloprim
60 mg/m^2 on Days 4 and 5 preceding natural killer cell infusion.
Andere namen:
  • Cytoxaan
25 mg/m^2 on Days 6 through 2 preceding natural killer cell infusion.
Andere namen:
  • Fludarabine
200 cGy Day 1 preceding natural killer cell infusion.
Andere namen:
  • TBI
Given day 0 - dose of 1.5-8.0 * 10^7/kg
Andere namen:
  • related donor haploidentical allogenic cell infusion
10 MU 3 times/week for a total of 6 doses beginning Day 0
Andere namen:
  • IL-2
  • Interleukine-2
Experimenteel: 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.
Andere namen:
  • Zyloprim
60 mg/m^2 on Days 4 and 5 preceding natural killer cell infusion.
Andere namen:
  • Cytoxaan
25 mg/m^2 on Days 6 through 2 preceding natural killer cell infusion.
Andere namen:
  • Fludarabine
Given day 0 - dose of 1.5-8.0 * 10^7/kg
Andere namen:
  • related donor haploidentical allogenic cell infusion
10 MU 3 times/week for a total of 6 doses beginning Day 0
Andere namen:
  • IL-2
  • Interleukine-2

Wat meet het onderzoek?

Primaire uitkomstmaten

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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of Patients Per Disease Response
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 maart 2008

Primaire voltooiing (Werkelijk)

1 augustus 2009

Studie voltooiing (Werkelijk)

1 augustus 2009

Studieregistratiedata

Eerst ingediend

3 april 2008

Eerst ingediend dat voldeed aan de QC-criteria

3 april 2008

Eerst geplaatst (Schatting)

4 april 2008

Updates van studierecords

Laatste update geplaatst (Werkelijk)

28 december 2017

Laatste update ingediend die voldeed aan QC-criteria

3 december 2017

Laatst geverifieerd

1 december 2017

Meer informatie

Termen gerelateerd aan deze studie

Andere studie-ID-nummers

  • 2007LS138
  • UMN-MT2007-19R (Andere identificatie: Blood and Marrow Transplantation Program)
  • UMN-WCC-53 (Andere identificatie: Women's Cancer Center, U of M)
  • UMN-0712M23462 (Andere identificatie: IRB, University of Minnesota)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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