Working... Menu

Natural Killer (NK) Cells in Cord Blood 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01619761
Recruitment Status : Recruiting
First Posted : June 14, 2012
Last Update Posted : January 28, 2019
American Cancer Society, Inc.
CLL Global Research Foundation
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.

The goal of this clinical research study is to learn if giving cells called natural killer (NK) cells after receiving a chemotherapy treatment and a UCB transplant can improve response in patients with leukemia, lymphoma, or MM. The safety of this treatment and whether NK cells can lessen the risk of graft vs. host disease (GVHD) will also be studied.

Patients with a disease that is CD20-positive will also receive rituximab on this study.

The first 3 patients enrolled on this study will not receive NK cells but will receive a cord blood transplant.

UCB and NK cells may be able to kill leukemia, lymphoma, or myeloma cells that remain in your body after chemotherapy treatment.

The UCB cells are also designed to increase blood production and strengthen your immune system.

This is an investigational study. Cyclophosphamide, fludarabine, melphalan, lenalidomide, and the UCB transplant procedure are all FDA approved and commercially available for the treatment of CLL. Cyclophosphamide is approved for the treatment of CLL. Fludarabine is approved for treatment of refractory CLL. Melphalan is approved for the treatment of multiple myeloma (MM) but has been used in transplant conditioning regimens. Lenalidomide is approved for the treatment of low risk myelodysplastic syndromes and for MM. Rituximab is approved for the treatment of CD20 positive B-cell lymphomas and chronic lymphocytic leukemia (in combination with chemotherapy).

The use of NK cells in patients is investigational.

Up to 13 participants will be enrolled in this study. All will be enrolled at MD Anderson.

Condition or disease Intervention/treatment Phase
Leukemia Chronic Lymphocytic Leukemia Drug: Lenalidomide Drug: Fludarabine monophosphate Drug: Melphalan Procedure: NK Infusion Procedure: CB Infusion Drug: Tacrolimus Drug: Mycophenolate mofetil Drug: Rituximab Drug: Cyclophosphamide Phase 1

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 13 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Natural Killer Cells In Allogeneic Cord Blood Transplantation
Actual Study Start Date : May 3, 2013
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019

Arm Intervention/treatment
Experimental: CB NK + Chemotherapy

Lenalidomide 10 mg by mouth day -8 to -2. Fludarabine 40 mg/m2 intravenous (IV) from day -7 to -4. Melphalan 140 mg/m2 IV on day -4. The NK cell infusion administered intravenously on day -2 over a period of 30 minutes. The NK dose infused will be 5x 10^6/kg. Remaining cells discarded if not needed for laboratory studies. On Day 0, unmanipulated products (smaller cord blood unit and remnant of the larger unit) infused. Tacrolimus 0.03 mg/kg or 0.015 mg/kg (ideal body weight) by vein starting on Day -2 and tapered around Day +180 if no GvHD is present. Mycophenolate mofetil 15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or by mouth Days -3 to Day +100 in the absence of GvHD.

CD20 positive participants admitted to hospital on day -9 to start hydration, receive rituximab 375 mg/m2 by vein on day -8, receive the designated preparative regimen on days -8 through -4. CD20 negative participants will not receive rituximab and admitted on day -8.

Drug: Lenalidomide

Treatment Plan #1: 10 mg by mouth on days -8 to -2.

Treatment Plan #2: 10 mg by mouth on days -7 to -2.

Other Names:
  • CC-5013
  • Revlimid

Drug: Fludarabine monophosphate
Treatment Plan #1 + #2: 40 mg/m2 by vein on days -7 to -4.
Other Names:
  • Fludarabine phosphate
  • Fludara

Drug: Melphalan
Treatment Plan #1: 140 mg/m2 by vein on day -4.
Other Name: Alkeran

Procedure: NK Infusion
Treatment Plan #1 + #2: The NK cell infusion administered intravenously on day -2 over a period of 30 minutes. The NK dose infused will be 5x 10^6/kg. Remaining cells will be discarded if not needed for laboratory studies.
Other Names:
  • Natural killer cell
  • NK

Procedure: CB Infusion
Treatment Plan #1 + #2: On Day 0, the unmanipulated products (smaller cord blood unit and the remnant of the larger unit) will be infused.
Other Names:
  • Cord blood
  • CB

Drug: Tacrolimus
Treatment Plan #1 + #2: 0.03 mg/kg or 0.015 mg/kg (ideal body weight) by vein starting on Day -2 and tapered around Day +180 if no GvHD is present.
Other Name: Prograf

Drug: Mycophenolate mofetil
Treatment Plan #1 + #2: 15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or by mouth Days -3 to Day +100 in the absence of GvHD.
Other Names:
  • CellCept
  • MMF

Drug: Rituximab
375 mg/m2 by vein on day -8 for CD20 positive participants.
Other Name: Rituxan

Drug: Cyclophosphamide
Treatment Plan #2: 50 mg by vein on Day -7.
Other Names:
  • Cytoxan
  • Neosar

Primary Outcome Measures :
  1. Success Rate [ Time Frame: 3 months ]
    Success is ability to generate adequate NK cells in a patient (a minimum of 3x10e8 natural killer (NK) cells). Success Rate is number of participants achieving success divided by total participants.

Secondary Outcome Measures :
  1. Treatment-Related Mortality (TRM) [ Time Frame: 100 days ]
    100-day treatment-related mortality (TRM) following the methods described by Thall et al.

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.

Layout table for eligibility information
Ages Eligible for Study:   up to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients must have one of the following hematologic malignancies: Acute Myelogenous Leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, FLT3 mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndrome, any disease beyond first remission.
  2. Myelodysplastic Syndrome (MDS): Primary or therapy related.
  3. Acute Lymphoblastic Leukemia (ALL): induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease. Patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with t(9;22) or t(4;11), hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma.
  4. Non-Hodgkin's Lymphoma (NHL) in second or third complete remission, refractory NHL, or relapsed NHL (including relapse post autologous hematopoietic stem cell transplant). Double hit lymphomas in first remission or more advanced disease.
  5. Small Lymphocytic Lymphoma (SLL), or Chronic Lymphocytic Leukemia (CLL) with progressive disease following standard therapy. Patients with progressive CLL following standard therapy who meet European Bone Marrow Transplant (EBMT) consensus guidelines of indications for allogeneic stem cell transplantation. This includes patients with (1) lack of response or early relapse within 1 year of receiving a purine analog-containing treatment regimen, (2) disease relapse within 2 years of receiving a purine analog combination therapy or after other therapies such as autologous stem cell transplantation, and (3) CLL associated with p53 mutations or deletions and/or del(17p) requiring therapy. Patients must have chemosensitive disease with at least a PR or SD with last treatment regimen.
  6. CML second chronic phase or accelerated phase.
  7. Hodgkin's Disease (HD): Induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant).
  8. Multiple Myeloma: stage II or III, symptomatic, secretory Multiple Myeloma requiring treatment.
  9. Age </= 75 years of age.
  10. Performance score of at least 80% by Karnofsky or 0 to 2 ECOG.
  11. Adequate major organ system function as demonstrated by: a. Left ventricular ejection fraction greater than 45%. b. Pulmonary function test (PFT) demonstrating a diffusion capacity of least 45% predicted. c. Creatinine < 1.6 mg/dL. d. SGPT/bilirubin </= to 2.0 x normal.
  12. All study participants must be registered into the mandatory Revlimid REMS program, and be willing and able to comply with the requirements of the Revlimid REMS program.
  13. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program.
  14. Negative Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 24 months or no previous surgical sterilization and willing to ongoing pregnancy testing while on treatment with lenalidomide.
  15. Woman with child bearing potential must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide.
  16. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy.
  17. Patients must have two CB units available which are matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. Each cord must contain at least 1.5 x 107 total nucleated cells/Kg recipient body weight (pre-thaw). Cord blood units will be procured through the NMDP (National Marrow Donor Program).
  18. Have identified a back up cells source in case of engraftment failure. The source can be autologous, related or unrelated.
  19. Patients who have had a prior autologous transplant are eligible.

Exclusion Criteria:

  1. Patients with known history of HIV/AIDS.
  2. Active CNS disease in patient with history of CNS malignancy.
  3. Patients with chronic active hepatitis or cirrhosis. If positive hepatitis serology, the Study Chair may deem the patient eligible based on the results of liver biopsy.
  4. Patients with known hypersensitivity to lenalidomide and/or rituximab.
  5. Patients who have a matched related donor who is eligible and willing to donate stem cells.

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): NCT01619761

Layout table for location contacts
Contact: Chitra M. Hosing, MD 713-792-8750

Layout table for location information
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
American Cancer Society, Inc.
CLL Global Research Foundation
Layout table for investigator information
Principal Investigator: Chitra M. Hosing, MD M.D. Anderson Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01619761     History of Changes
Other Study ID Numbers: 2011-0493
NCI-2012-02071 ( Registry Identifier: NCI CTRP )
13369 ( Other Grant/Funding Number: American Cancer Society )
First Posted: June 14, 2012    Key Record Dates
Last Update Posted: January 28, 2019
Last Verified: January 2019

Layout table for additional information
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:
Cord blood
Umbilical cord blood
Chronic Lymphocytic Leukemia
Natural killer cells
Graft versus host disease
Fludarabine Phosphate

Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Fludarabine phosphate
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Calcineurin Inhibitors