Allogeneic Natural Killer (NK) Cells for Ovarian, Fallopian Tube, Peritoneal and Metastatic Breast Cancer

NCT01105650 | Completed Phase 2 Results DMC

• 3 other identifiers: 2009LS142MT2009-301003M78876
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center phase II trial designed to optimize a clinical platform of lymphodepleting chemotherapy and T-cell suppression to promote the persistence, function, and expansion of allogeneic natural killer (NK) cells in patients with recurrent ovarian, fallopian tube, primary peritoneal cancer and advanced metastatic breast cancer.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer; Breast Cancer

Keywords

recurrent ovarian cancer; recurrent fallopian tube cancer; recurrent primary peritoneal cancer; refractory ovarian cancer; refractory fallopian tube cancer; refractory peritoneal cancer; metastatic breast cancer

Outcome Measures

Primary Outcomes (1)

• Response Rate

  Response includes Complete Response (CR), Partial Response (PR), and Stable Disease (SD) as defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v.1.1) for target lesions and assessed by CT or MRI. Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease.

  Month 3

Secondary Outcomes (3)

• Time to Disease Progression

  1 Year

• Number of Participants With Progressive Disease at One Year

  1 Year

• Overall Survival

  1 Year

Study Arms (4)

Arm 1: CsA

EXPERIMENTAL

Patients receiving Cyclosporine (CsA) and Natural Killer (NK) cells infusion (created from donor lymphapheresis) after preparative regimen of Fludarabine and Cyclophosphamide. Interleukin-2 (IL-2) 6 million units 3 times a week x 6 doses given post NK cell infusion.

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Cyclosporine; Biological: Natural killer cells; Drug: IL-2; Drug: Interleukin-2

Arm 2: CsA plus Methylprednisolone (10mg)

EXPERIMENTAL

Patients receiving Cyclosporine (CsA), methylprednisolone and natural killer cells (NK) infusion (created from donor lymphapheresis) after preparative regimen of Fludarabine and Cyclophosphamide. Interleukin-2 (IL-2) 6 million units 3 times a week x 6 doses given post NK cell infusion.

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Cyclosporine; Biological: Natural killer cells; Drug: IL-2; Drug: Methylprednisolone; Drug: Interleukin-2

Arm 3: CsA plus Methylprednisolone (1 mg)

EXPERIMENTAL

Patients receiving Cyclosporine (CsA), methylprednisolone and natural killer (NK) cells infusion (created from donor lymphapheresis) after preparative regimen of Fludarabine and Cyclophosphamide. Interleukin-2 (IL-2) 6 million units 3 times a week x 6 doses given post NK cell infusion.

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Cyclosporine; Biological: Natural killer cells; Drug: IL-2; Drug: Methylprednisolone; Drug: Interleukin-2

Arm 4: CsA minus Methylprednisolone

EXPERIMENTAL

Patients receiving Cyclosporine (CsA), no methylprednisolone, eliminating IL-2 doses 4-6 and receiving Natural Killer (NK) cells infusion (created from donor lymphapheresis) after preparative regimen of Fludarabine and Cyclophosphamide. Interleukin-2 (IL-2) 6 million units 3 times a week x 3 doses given post NK cell infusion.

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Cyclosporine; Biological: Natural killer cells; Drug: Interleukin-2

Interventions

Fludarabine DRUG

Administered intravenously, 25 mg/m\^2, days -6 through -2 (5 days).

Also known as: Fludara

Arm 1: CsA; Arm 2: CsA plus Methylprednisolone (10mg); Arm 3: CsA plus Methylprednisolone (1 mg); Arm 4: CsA minus Methylprednisolone

Cyclophosphamide DRUG

Administered intravenously, 60 mg/kg, days -5 and -4.

Also known as: Cytoxan

Arm 1: CsA; Arm 2: CsA plus Methylprednisolone (10mg); Arm 3: CsA plus Methylprednisolone (1 mg); Arm 4: CsA minus Methylprednisolone

Cyclosporine DRUG

Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14

Also known as: Cyclosporine A, CsA

Arm 1: CsA; Arm 2: CsA plus Methylprednisolone (10mg); Arm 3: CsA plus Methylprednisolone (1 mg); Arm 4: CsA minus Methylprednisolone

Natural killer cells BIOLOGICAL

Administered by infusion over less than 1 hour, no more than 8.0 x 10\^7 cells/kg will be given.

Arm 1: CsA; Arm 2: CsA plus Methylprednisolone (10mg); Arm 3: CsA plus Methylprednisolone (1 mg); Arm 4: CsA minus Methylprednisolone

IL-2 DRUG

Will be given subcutaneously at 9 million units 3 times a week for a total of 6 doses, beginning 4 hours after NK cell infusion. (For patients weighing less than 45 kilograms, will be given at 5 million units/m\^2 3 times per week for 6 doses).

Also known as: Interleukin-2

Arm 1: CsA; Arm 2: CsA plus Methylprednisolone (10mg); Arm 3: CsA plus Methylprednisolone (1 mg)

Methylprednisolone DRUG

Administered intravenously (IV) 10 mg/kg Days -2 to +4 and 1 mg/kg Days +5 to +9

Also known as: Medrol

Arm 2: CsA plus Methylprednisolone (10mg); Arm 3: CsA plus Methylprednisolone (1 mg)

Interleukin-2 DRUG

Will be given subcutaneously at million units 3 times a week for a total of 3 doses, beginning 4 hours after NK cell infusion. (For patients weighing less than 45 kilograms, will be given at 3 million units/m\^2 3 times per week for 6 doses).

Also known as: IL-2

Arm 1: CsA; Arm 2: CsA plus Methylprednisolone (10mg); Arm 3: CsA plus Methylprednisolone (1 mg); Arm 4: CsA minus Methylprednisolone

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 that has failed or progressed after at least 2 prior salvage chemotherapy regimens (directed at recurrent/metastatic disease).
• Diagnosis of metastatic breast cancer (female or male) that has progressed on or failed at least one salvage chemotherapy regimen for metastatic disease and that meets the following disease specific related criteria:
• If estrogen receptor or progesterone receptor positive must have progressed on prior hormonal therapy and/or
• if HER2-neu positive must have progressed on trastuzumab, lapatinib, or similar agent
• Women with a history of both cancers are eligible for this study provided that they currently meet eligibility for one of the diseases. Women who have had another malignancy and have been disease free for at least 3 year, or with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
• Measurable disease per disease specific Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 - patients with bone as their only site of disease will not be eligible.
• If history of brain metastases must be 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 clinical signs or symptoms suggestive of brain metastases.
• Available related HLA-haploidentical natural killer (NK) cell donor (by at least class I serologic typing at the A\&B locus)
• Age 18 years or older
• Karnofsky performance status \> or = 50%
• Adequate organ function as determined by the following criteria within 14 days of study enrollment
• Bone marrow: platelets \> or = 80,000 x 10\^9/L and hemoglobin \> or = 9 g/dL, unsupported by transfusions; absolute neutrophil count (ANC) \> or = 1000 x 10\^9/L, unsupported by growth colony stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF)
• Renal function: creatinine (Cr) \< or = 2.0 mg/dL
• Liver function: Aspartate aminotransferase (AST), Alanine transaminase (ALT), total bilirubin, alkaline phosphatase \< 5 times upper limit of institutional normal (ULN)
• Cardiac: Left ventricular ejection fraction \>40% (within 28 days of treatment start)

You may not qualify if:

• Pregnant or nursing - 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. Participants of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy and agree to use adequate birth control during study treatment
• Active infection - subjects must be afebrile, off antibiotics, and with no uninvestigated radiologic lesions (infiltrates or lesions with negative cultures or biopsies) are allowed

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Breast Neoplasms

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Cyclosporine; IL32 protein, human; Interleukin-2; Methylprednisolone

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Lymphokines; Proteins; Biological Factors; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Results Point of Contact

• Title: Dr. Melissa Geller
• Organization: Masonic Cancer Center, University of Minnesota

gelle005@umn.edu

612-626-3111

Study Officials

• Melissa Geller, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• 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 14, 2010
• First Posted: April 16, 2010
• Study Start: July 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: December 28, 2017
• Results First Posted: February 24, 2017

Record last verified: 2017-12

Locations

US (1)