A Phase I Study of NK Cell Infusion Following Allogeneic Peripheral Blood Stem Cell Transplantation From Related or Matched Unrelated Donors in Pediatric Patients With Solid Tumors and Leukemias

Summary

Background:

* Bone marrow stem cells, which are found in the bone marrow and blood stream, can be collected and transplanted to treat a variety of types of cancer in a process known as hematopoietic stem cell transplantation (HSCT). When stem cells are taken from one person, most commonly a sibling or a family member, and then given to another person, this is referred to as allogeneic HSCT. Allogeneic HSCT has proven to be an especially effective treatment for patients with some types of cancers of the blood (leukemia) and certain solid tumors. The transplanted stem cells travel to the patient's bone marrow and begin producing normal blood cells, and also attack patients cancer cells.
* Because allogenic HSCT does not always prevent the cancer from returning, researchers are interested in determining whether another type of immune cell taken from the stem cell donors white blood cells, called a "natural killer" (NK) cell, can be given in addition to the HSCT to help fight the tumor. In the laboratory, NK cells have been shown to kill tumor cells, but it is not yet know if this will occur when given to patients after HSCT.

Objectives:

* To determine the safety, effectiveness, and immune system response of giving NK white blood cells to individuals who have received allogeneic HSCT.
* To identify possible side effects from the treatment.

Eligibility:

* Donors: Stem cell donors whose blood matches one of the recipients on six out of six human leukocyte antigen (HLA) (blood immune marker) types. The donor may not be the identical twin of a recipient.
* Recipients: Individuals between 4 and 35 years of age who have been diagnosed with pediatric solid tumors that have not responded to standard treatment, or individuals between 4 and 18 years of age who have been diagnosed with leukemia that has not responded to standard treatment.
* Other eligibility requirements which include a physical exam and blood laboratory evaluation are included to make sure it is safe for both the donor to donate and the recipient to undergo the transplant procedure.

Design:

* Donors and recipients will be screened with a full medical history and physical examination, and will provide blood and urine samples; recipients will have tumor imaging studies and other tests as required by the researchers.
* Donors:
* Participants will receive filgrastim injections (to stimulate the bone marrow) for 1 week to make stem cells travel from bone marrow to blood.
* Participants will provide stem cells and NK cells through apheresis.
* Recipients:
* Participants will have three cycles of chemotherapy to treat the underlying cancer and weaken the immune system so that it will accept the donor cells.
* Participants will then receive preparative chemotherapy for the transplant and two days after the last dose of chemotherapy, participants will have allogenic HSCT using the donated stem cells.
* Participants will receive an infusion of NK cells on days 7 and 35 after the HSCT. - Participants will remain in the hospital for monitoring after the HSCT and NK cell treatments, and will be followed closely as outpatients for the first 6 months after the transplant and then less frequently for at least 5 years.

Conditions

• Leukemia
• Lymphoma

Interventions

BIOLOGICAL

Natural Killer (NK) Cell Infusion

Post-transplant Day 21 (plus-minus 3 days): (1 x 10(5), 1 x 10(6) or 1 x 10(7) natural killer (NK) cells/kg by intravenous (IV) infusion. Followed by a second NK cell infusion of the same cell dose, on Day 49 plus-minus 7 days.

BIOLOGICAL

Stem Cell Infusion

Transplant Day 0: \>4 x 10(6)/kg cluster of differentiation 34 (CD34)+ stem cells by IV infusion Filgrastim, 5 microgram/kg per day subcutaneous (SQ) from day 0 until absolute neutrophil count (ANC) \>5000/microliters x2

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Nirali N Shah, M.D. · National Cancer Institute (NCI)

Study Design

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

4 Years

Max Age

35 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2011-01-29

Primary Completion

2018-06-28

Completion

2018-06-28

FDA Drug

Yes

Countries

• United States

Study Locations