Symptoms and General Pathology

All Conditions

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Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

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Antineoplastic Agents

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Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Mitogens

Interleukin-2

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Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

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Anti-HIV Agents

Anti-Retroviral Agents

* Lymphodepleting Preparative Regimen: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 2 hours on days -5 and -4.
* Donor Leukapheresis: Peripheral blood cells are collected from haploidentical related donors over 5 hours on day -1.
* CIML NK Cells: Patients undergo CIML NK cell infusion over 15-60 minutes on day 0.
* Interleukin-2: Patients receive aldesleukin SC every other day for 2 weeks starting on day 1 (total of 7 doses)

The recipient will begin a lymphodepleting preparative regimen of fludarabine and cyclophosphamide on Day -6. The haploidentical donor identified by HLA matching of the immediate family members will undergo non-mobilized large volume (20-L) leukapheresis on Day -1, and the NK cell product will be infused into the recipient on Day 0. Subcutaneous IL-2 will begin approximately 2-4 hours after infusion and will continue every other day through Day 12 for a total of 7 doses.

* Lymphodepleting Preparative Regimen: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 2 hours on days -5 and -4.
* Donor Leukapheresis: Peripheral blood cells are collected from haploidentical related donors on Day -1.
* CIML NK Cells: Patients undergo CIML NK cell infusion on Day 0.
* Subcutaneous ALT-803 will begin approximately 4 hours after the infusion and will continue for a total of 2 doses (Days 0 and 5).

* Lymphodepleting Preparative Regimen: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 2 hours on days -5 and -4.
* Donor Leukapheresis: Peripheral blood cells are collected from haploidentical related donors on Day -1
* CIML NK Cells: Patients undergo CIML NK cell infusion on Day 0
* Subcutaneous IL-2 will begin approximately 2-4 hours after infusion and will continue every other day through Day 12 for a total of 7 doses

-The haploidentical donor identified by HLA matching of the immediate family members (parents, siblings, and children) will undergo non-mobilized leukapheresis on Day -1. Peripheral blood mononuclear cells (PBMCs) will be collected using standard collection techniques.

Leukapheresis

Cytokine-induced killer cells

IL-2

ALT-803

-Screening, Day 0 prior to CIML NK infusion, Day 1, Day 3, Day 7, Day 8, Day 10, Day 14, Day 21, Day 28, Day 42, Day 60, Day 100, 6 months, 9 months, 12 months, and at disease relapse

Peripheral blood for correlative studies

-Screening, Day 8, Day 14, Day 28, Between Day 42 and 60, Day 100, at disease relapse

Bone marrow for correlative studies

Amanda Cashen, M.D.

This phase I/2 trial studies the side effects and best dose of activated natural killer cells in treating patients with relapsed or refractory acute myeloid leukemia and myelodysplastic syndromes. Giving chemotherapy before a donor natural killer cell infusion helps stop the growth of cancer cells and stops the patient's immune system from rejecting the donor's natural killer cells. Modified natural killer cells may help the body build an immune response to kill cancer cells. Aldesleukin (interleukin-2) may stimulate the white blood cells (including natural killer cells) to kill leukemia cells.

In the phase II and pediatric portion of the study, the investigators intend to use maximal tolerated or tested (MT/TD) CIML NK cell dose as determined from the phase I part of this study. The phase II portion of the study also replaces IL-2 with ALT-803. The rationale for this change is to support the donor derived NK cells in vivo after adoptive transfer.

With amendment 16, the decision was made to return to the use of rhIL-2 support instead of ALT-803.

Cytokine-induced Memory-like NK Cells in Patients With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

A Phase 1/2 Study of Cytokine-Induced Memory-Like NK Cells in Patients With AML or MDS

Defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity (DLT) or the maximum dose if less than or equal to 1 patient suffers a DLT at the maximum dose.

* Complete remission rate (CR): Morphologically leukemia free state (i.e. bone marrow with \<5% blasts by morphologic criteria and no blasts with Auer rods, no evidence of extramedullary leukemia) and absolute neutrophil count ≥1000 /μL and platelets ≥100,000 /μL. Patient must be independent of transfusions
* Complete Remission with Incomplete Blood Count Recovery (CRi): All of the above criteria for CR must be met, except that absolute neutrophils \<1000 /μL or platelets \<100,000 /μL in the blood.

* Graded using the National Cancer (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Related indicates possibly, probably, or definitely related to study treatment.
* Adverse events will be collected from Day 0 to Day +35; however, bone marrow suppression (ANC \< 500/uL/µL) and AEs of GVHD involving the liver, skin, or GI tract will be recorded to Day 100.

DOR is defined only for patients who achieve a complete remission (CR), complete remission with incomplete blood count recovery (CRi), marrow complete response (mCR), or partial remission (PR), and is measured from the first date of attaining CR or PR until the date of disease progression or death.

TTP is defined as the time from date of first dose of fludarabine until evidence of disease progression.

DFS is defined as the time from the day CR, mCR, or CRi is documented until disease progression or death.

OS is defined from the date of first dose of fludarabine on this study until death.

* Graded using the National Cancer (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Related indicates possibly, probably, or definitely related to study treatment.
* AEs will be collected from Day 0 to Day +35; however, bone marrow suppression (ANC \< 500/uL/µL) and AEs of GVHD involving the liver, skin, or GI tract will be recorded to Day 100.

American Society of Clinical Oncology

American Society of Hematology

Gabrielle's Angel Foundation

The Leukemia and Lymphoma Society

National Cancer Institute (NCI)

ImmunityBio, Inc.

Washington University School of Medicine

-Adverse events \& all-cause mortality were not collected for donors. All-cause mortality for all others were collected through completion of follow-up.

Phase I Dose Level 1: 0.5 x 10^6/kg CIML NK Cells

Phase I Dose Level 2: 1.0 x 10^6/kg CIML NK Cells

Phase I Dose Level 3: Maximum NK Cell/Number kg

Lead-in Cohort & Phase II (ALT-803): Maximum NK Cell/Number kg

Phase II (IL-2): Maximum NK Cell/Number kg

Pediatric Cohort: Maximum NK Cell/Number kg

Donors

Phase I Dose Level 3: 1.0 x 10^7/kg CIML NK Cells

Lead-in Cohort & Phase II (ALT-803): 1.0 x 10^7/kg CIML NK Cells

Phase II (IL-2): 1.0 x 10^7/kg CIML NK Cells

Pediatric Cohort: 1.0 x 10^7/kg CIML NK Cells

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Phase I

Maximal Tolerated or Tested Dose (MT/TD) of CIML-NK Cells (Phase I)

Complete Remission Rate (CR/CRi) in Participants With Relapsed or Refractory AML Following CIML NK Therapy (Phase II)

Chills : Grade 2

Anorexia : Grade 2

Anorexia : Grade 3

Alanine aminotransferase increased : Grade 1

Alanine aminotransferase increased : Grade 3

Aspartate aminotransferase increased : Grade 1

Aspartate aminotransferase increased : Grade 3

Fever : Grade 3

Hypertension : Grade 2

Hyperammonemia : Grade 2

Capillary leak syndrome : Grade 2

Hypokalemia : Grade 1

Hypophosphatemia : Grade 4

Hypocalcemia: Grade 1

Hypomagnesemia: Grade 1

Hyperkalemia: Grade 1

Headache: Grade 1

Headache: Grade 2

Myalgia: Grade 1

Arthralgia: Grade 1

Fatigue: Grade 1

Injection site reaction: Grade 2

Epistaxis: Grade 3

Hematoma: Grade 1

Paresthesia: Grade 1

Pain: Grade 1

Pain: Grade 2

Sinus tachycardia: Grade 1

Tachypnea: Grade 1

Vomiting: Grade 1

Skin induration: Grade 1

Malaise: Grade 1

Febrile neutropenia: Grade 1

Flushing: Grade 1

Hypoalbuminemia: Grade 1

Safety of CIML NK Cells as Measured by the Number of Participants With Treatment Related Adverse Events (Pediatric Cohort)

Response Assessed According to IWG Criteria (Phase 1, Phase II, and Pediatric)

Only for patients who achieve a complete remission (CR), complete remission with incomplete blood count recovery (CRi), marrow complete response (mCR), or partial remission (PR).

Duration of Remission (DOR) (Phase I, Phase II, and Pediatric)

Not evaluable: 2 patients Phase 1 Dose Level 1 (didn't receive adequate cell dose, expired before infusion). 2 patients Phase I Dose Level 2 (expired before infusion, received haplo transplant before PD). 3 patients Phase I Dose Level 3 (no bone marrow biopsy, 2-expired before PD). 2 patients Phase II IL-2 (2-no bone marrow biopsy). 1 patient Phase II ALT-803 (expired before response assessment). 2 patients Pediatric (expired before PD, poor bone marrow sample).

Time to Progression (Phase I, Phase II, and Pediatric)

Only those patients with CR, mCR, or CRi are evaluable for this outcome measure.

Disease Free Survival (DFS) (Phase I, Phase II, and Pediatric)

Overall Survival (OS) (Phase I, Phase II, and Pediatric)

Nausea: Grade 1

Nausea: Grade 2

Diarrhea: Grade 1

Diarrhea: Grade 2

Aspartate aminotransferase increased: Grade 1

Alanine aminotransferase increased: Grade 1

Proteinuria: Grade 1

Proteinuria: Grade 2

Blood bilirubin increased: Grade 1

Blood bilirubin increased: Grade 2

Alkaline phosphatase increased: Grade 1

Sinus tachycardia: Grade 2

Febrile neutropenia: Grade 3

Malaise: Grade 2

Rigors after IL-2 administration: Grade 2

Hypoxia: Grade 2

Dyspnea: Grade 2

Confusion: Grade 2

Confusion: Grade 3

Lethargy: Grade 2

Chills: Grade 2

Injection site reaction: Grade 1

Rigors after CIML NK cell infusion

Alopecia: Grade 2

Fatigue: Grade 2

Fatigue: Grade 3

Anorexia: Grade 1

Anorexia: Grade 2

Anorexia: Grade 3

Rigors: Grade 1

Rigors: Grade 2

Hypotension: Grade 1

Hypotension: Grade 2

Insomnia: Grade 2

Encephalopathy: Grade 3

Wheezing: Grade 2

Pulmonary edema: Grade 1

Pulmonary edema: Grade 2

Pleural effusion: Grade 2

Cytokine release syndrome: Grade 1

Cytokine release syndrome: Grade 2

Capillary leak syndrome: Grade 2

Fever: Grade 1

Fever: Grade 2

Infusion related reaction: Grade 1

Infusion related reaction: Grade 2

Infusion related reaction: Grade 3

Hypertension: Grade 2

Hypertension: Grade 3

Neutrophil count decreased: Grade 4

Lymphocyte count decreased: Grade 4

White blood cell decreased: Grade 4

Mucositis oral: Grade 1

Mucositis oral: Grade 2

Headache: Grade 3

Sepsis: Grade 4

Lung infection: Grade 3

Platelet count decreased: Grade 1

Platelet count decreased: Grade 4

Pulmonary alveolar hemorrhage: Grade 2

Rash maculo-papular: Grade 1

Abdominal pain: Grade 1

Hyponatremia: Grade 1

Hyponatremia: Grade 3

Hematuria: Grade 2

Pruritus: Grade 1

Toxicity as Measured by the Number of Participants With Treatment Related Adverse Events (Phase I and Phase II)

Spots Global Cancer Trial Database for peripheral blood for correlative studies