Natural Killer (NK) Cells in Cord Blood Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01619761
First received: June 12, 2012
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

The goal of this clinical research study is to learn if giving cells called natural killer (NK) cells after receiving fludarabine, melphalan, lenalidomide, 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.


Condition Intervention 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
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Natural Killer Cells In Allogeneic Cord Blood Transplantation

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Success Rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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:
  • Treatment-Related Mortality (TRM) [ Time Frame: 100 days ] [ Designated as safety issue: No ]
    100-day treatment-related mortality (TRM) following the methods described by Thall et al.


Estimated Enrollment: 13
Study Start Date: May 2013
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 106/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
10 mg by mouth on days -8 to -2.
Other Names:
  • CC-5013
  • Revlimid
Drug: Fludarabine monophosphate
40 mg/m2 by vein on days -7 to -4.
Other Names:
  • Fludarabine phosphate
  • Fludara
Drug: Melphalan
140 mg/m2 by vein on day -4.
Other Name: Alkeran
Procedure: NK Infusion
The NK cell infusion will be administered intravenously on day -2 over a period of 30 minutes. The NK dose infused will be 5x 106/kg. Remaining cells will be discarded if not needed for laboratory studies.
Other Names:
  • Natural killer cell
  • NK
Procedure: CB Infusion
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
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
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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, or relapse (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 12 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01619761

Contacts
Contact: Chitra M. Hosing, MD 713-792-8750

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Chitra M. Hosing, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01619761     History of Changes
Other Study ID Numbers: 2011-0493
Study First Received: June 12, 2012
Last Updated: February 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Chronic Lymphocytic Leukemia
CLL
Cord blood
CB
Umbilical cord blood
UCB
Natural killer cells
NK
Graft versus host disease
GVHD
Lenalidomide
CC-5013
Revlimid
Fludarabine
Fludarabine Phosphate
Fludara
Melphalan
Alkeran
Rituximab
Rituxan

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Melphalan
Fludarabine
Fludarabine monophosphate
Rituximab
Lenalidomide
Mycophenolic Acid
Mycophenolate mofetil
Tacrolimus
Vidarabine
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on July 24, 2014