Immunotherapy With NK Cell, Rituximab and Rhu-GMCSF in Non-Myeloablative Allogeneic Stem Cell Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00383994
Recruitment Status : Active, not recruiting
First Posted : October 4, 2006
Last Update Posted : November 30, 2017
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find out if giving a boost of natural killer (NK) cells from a donor combined with Rituxan (rituximab), can help to control disease in patients who have already received an allogeneic stem cell transplant. The safety of this treatment will also be studied. Participants have recurrent chronic lymphocytic leukemia (CLL) or lymphoma after non-myeloablative stem cell transplantation.

Primary Objectives:

1.0 To determine the safety of Natural Killer (NK) cells and Rituximab + rhu-Granulocyte-macrophage colony-stimulating factor (GMCSF) in patients with persistent or recurrent B-cell lymphoid malignancies after non-myeloablative stem cell transplantation.

2.0 To determine factors associated with response.

Condition or disease Intervention/treatment Phase
Lymphoma Leukemia Transplantation, Stem Cell Lymphoid Malignancies Disorder Related to Transplantation Drug: GM-CSF Drug: Rituximab Biological: NK Cell Infusion Phase 1

Detailed Description:

Rituximab is designed to attach to lymphoma cells, causing them to die. GM-CSF and NK cells may increase rituximab's ability to kill these cells.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have your complete medical history recorded and a physical exam. Your blood (about 2 tablespoons) will be collected for routine tests. A bone marrow aspirate will be performed. To collect a bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. You will have computerized tomography (CT) scans as well as positron emission tomography (PET) or gallium scans to learn the status of your disease. Women who are able to have children must have a negative blood or urine pregnancy test.

If you are found eligible to take part in this study, you will receive treatment as an outpatient. You will receive GM-CSF 3 times a week for 4 weeks through a vein, starting the day before you receive the administration of rituximab. You will receive rituximab over 4 to 8 hours through a vein, once weekly for 4 weeks. You will also get a boost of NK cells from the same donor from whom you received your original transplant. These cells will be infused through a vein (over 30 to 60 minutes) after the 4th dose of rituximab. If you are receiving a cell infusion from somebody who you are not related to, the infusion may have to be done later if cells were not available as scheduled.

The CliniMACS System is a medical device that is used to separate types of blood cells from blood that is removed from the body during leukapheresis. These separated cells are processed for use in treatments such as stem cell transplants.

During this treatment, you will be examined as needed, and blood samples (1 tablespoon once or twice a week) will be taken for routine tests. You may need to receive blood transfusions during this study if your blood cell counts remain low.

You may be taken off this study if your disease gets worse or intolerable side effects occur.

You will have long-term, follow-up visits while on study. You will be seen at 4 to 6 weeks after you receive NK cell infusion; every 3 months during the first year; and then once a year. During each of these visits, you will have CT and PET scans, a bone marrow biopsy, and blood drawn (about 4 teaspoons) to learn the status of your disease.

This is an investigational study. Rituximab and GM-CSF are FDA approved and commercially available. NK cells are authorized by the FDA for use in research only. Up to 40 participants will take part in this study. All will be enrolled at the University of Texas (UT) MD Anderson Cancer Center.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Immunotherapy With NK Cell, Rituximab and Rhu-GMCSF in Non-Myeloablative Allogeneic Stem Cell Transplantation
Actual Study Start Date : September 2006
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019

Arm Intervention/treatment
Experimental: Immunotherapy with NK Cell, Rituximab + GM-CSF

Immunotherapy in Non-myeloablative Allogeneic Stem Cell Transplantation

GM-CSF = Granulocyte-Macrophage Colony-Stimulating Factor

Drug: GM-CSF
250 micrograms subcutaneously 3 times a week for 4 weeks starting a day before the administration of Rituximab.
Other Names:
  • Sargramostim
  • Leukine
Drug: Rituximab
375 mg/m^2 by vein followed by 1000 mg/m^2 weekly for 3 weeks for a total of 4 doses.
Other Name: Rituxan
Biological: NK Cell Infusion
NK cells will be infused one week after the fourth dose of Rituximab and GM-CSF.

Primary Outcome Measures :
  1. Dose-limiting toxicities (DLTs) for NK cells infusions after non-myeloablative transplantation for lymphoid malignancies [ Time Frame: Evaluated for toxicity within 6 weeks of treatment ]
    Maximum tolerated dose (MTD) is the highest dose with 10 patients treated and 5 or fewer patients with DLT.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with previous diagnosis of CD20+ B-cell CLL and non-Hodgkin's lymphoma who have failed standard conventional chemotherapy, and who had persistent disease at 3 months, or progressive disease after non-myeloablative allogeneic transplantation.
  2. Donor willingness to donate peripheral blood (same donor of the original transplant).
  3. Negative Beta HCG in a woman with child bearing potential defined as not post-menopausal for 12 months or not previous surgical sterilization.

Exclusion Criteria:

  1. Pregnancy or lactation
  2. HIV , HTLV-I or hepatitis.
  3. Active infection(s) >/= grade 3.
  4. Severe active concomitant medical or psychiatric illness.
  5. Concurrent active GVHD requiring tacrolimus.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00383994

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Principal Investigator: Issa F. Khouri, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00383994     History of Changes
Other Study ID Numbers: 2005-0234
NCI-2012-01375 ( Registry Identifier: NCI CTRP )
First Posted: October 4, 2006    Key Record Dates
Last Update Posted: November 30, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Chronic Lymphocytic Leukemia
Non-Hodgkin's Lymphoma
B-Cell Lymphoma
granulocyte-macrophage colony-stimulating factor
NK Cells
Non-myeloablative Allogeneic Stem Cell Transplantation
Stem Cell Transplant

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents