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Trial record 40 of 670 for:    Recruiting, Not yet recruiting, Available Studies | "Bone Marrow Diseases"

Personalized Natural Killer (NK) Cell Therapy in Cord Blood Transplantation (CBT)

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ClinicalTrials.gov Identifier: NCT02727803
Recruitment Status : Recruiting
First Posted : April 5, 2016
Last Update Posted : June 25, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Cancer Prevention Research Institute of Texas
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if giving cells called natural killer (NK) cells after receiving 1 of 3 pre-treatment plans and a UCB transplant can improve response in patients with MDS, leukemia, lymphoma, or MM. The safety of this treatment and whether NK cells can lessen the risk of graft versus host disease (GVHD) will also be studied.

If the disease is CD20 positive, you will also receive rituximab on this study in addition to what is described above. CD20 is a type of marker for white blood cells. White blood cells help protect the body from infections.

NK cells may kill cancer cells that remain in your body after your last chemotherapy treatment. The NK cells will be separated from umbilical cord blood. The device used in the laboratory to separate the NK cells is called a CliniMACS. These separated NK cells will then be grown in the lab to increase the number of NK cells that can be given to you by vein.

Based on your genes, your NK cells may not recover as quickly after transplant. Before the transplant, blood will be collected for genetic testing as part of standard screening tests. If the genetic test shows that your NK cells will not recover as quickly after transplant, you will receive the NK cell infusion.

This is an investigational study. Busulfan, fludarabine, clofarabine, ATG, rituximab, cyclophosphamide, mesna, and melphalan are FDA approved and commercially available for the treatment of blood cancers and/or for use in stem cell transplant. The way the researchers process the NK cells and the way they are infused is not FDA approved. These processes are currently being used for research purposes only.

Up to 100 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Myeloma Myeloproliferative Diseases Drug: Busulfan Drug: Fludarabine Drug: Clofarabine Drug: Rabbit ATG Radiation: Total Body Irradiation (TBI) Procedure: Cord Blood Infusions Drug: Rituximab Drug: Cyclophosphamide Procedure: Natural Killer Cell Infusion Drug: Melphalan Drug: Mesna Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Personalized Natural Killer (NK) Cell Therapy in Cord Blood Transplantation
Actual Study Start Date : May 19, 2016
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2021


Arm Intervention/treatment
Experimental: Treatment Plan #1

Participants with ALL, AML, NHL, CLL, CML, HD, and MM who are >/= 18 and </= 55 years old receive myeloablative regimen #1. Patients > 55 but < 65 years who have a Performance Status of 0 or 1 and no comorbidities may receive the Myeloablative Regimen 1 at the discretion of the investigator(s).

Participants receive busulfan, fludarabine, clofarabine, and antithymocyte globulin (ATG) by vein, as well as total body irradiation (TBI).

Drug: Busulfan
Busulfan 32 mg/m2 by vein test dose administrated either as an outpatient before Day -14 or as an inpatient on Day -9. Busulfan pharmacokinetics performed. Doses of days -7 to -4 subsequently adjusted to target an area under curve (AUC) of 4,000 microMol.min-1. In the event that PK adjusting was not possible a dose of busulfan of 130 mg/m2 administered.
Other Names:
  • Busulfex
  • Myleran

Drug: Fludarabine

Treatment Plan #1: 10 mg/m2 by vein on Days -7 to -4. Participants </= 2 years of age receive Fludarabine 1.3 mg/kg.

Treatment Plan # 2: 40 mg/m2 by vein on Days -6 to -3.

Treatment Plan # 3: 40 mg/m2 by vein on Days -5 to -2.

Other Names:
  • Fludarabine phosphate
  • Fludara

Drug: Clofarabine
30 mg/m2 by vein on Days -7 to -4.
Other Names:
  • Clofarex
  • Clolar

Drug: Rabbit ATG
Treatment Plan # 1: 1.25 mg by vein on Day -9 and 1.75 mg by vein on Day -8. Treatment Plan # 2 1.25 mg by vein on Day -8 and 1.75 mg by vein on Day -7. Treatment Plan # 3: 1.25 mg by vein on Day -7 and 1.75 mg by vein on Day -6.
Other Names:
  • ATG (Rabbit)
  • Rabbit Antithymocyte Globulin
  • Rabbit Antilymphocyte Globulin
  • rATG
  • Thymoglobulin

Radiation: Total Body Irradiation (TBI)

Treatment Plan #1: TBI 2 Gy in AM on Day -3.

Treatment Plan #2: TBI 2 Gy on Day -1.

Other Names:
  • Radiation Therapy
  • XRT

Procedure: Cord Blood Infusions
Cord blood infusions on Day 0.

Procedure: Natural Killer Cell Infusion
NK Cell Infusion (C2C2 subgroup only) on Day +30 to Day +80.

Experimental: Treatment Plan #2

Participants with AML, ALL, NHL, CLL, CML, HD and MM who are > 55 and </= 80 years old or of any age with co-morbid condition that in the opinion of the investigators would preclude myeloablative therapy receive Nonmyeloablative Regimen #2.

Participants receive rituximab (only for those with CD20+ malignancies) or no rituximab (without CD20+ malignancies), fludarabine, cyclophosphamide, mesna, and ATG by vein, as well as total body irradiation (TBI).

Drug: Fludarabine

Treatment Plan #1: 10 mg/m2 by vein on Days -7 to -4. Participants </= 2 years of age receive Fludarabine 1.3 mg/kg.

Treatment Plan # 2: 40 mg/m2 by vein on Days -6 to -3.

Treatment Plan # 3: 40 mg/m2 by vein on Days -5 to -2.

Other Names:
  • Fludarabine phosphate
  • Fludara

Drug: Rabbit ATG
Treatment Plan # 1: 1.25 mg by vein on Day -9 and 1.75 mg by vein on Day -8. Treatment Plan # 2 1.25 mg by vein on Day -8 and 1.75 mg by vein on Day -7. Treatment Plan # 3: 1.25 mg by vein on Day -7 and 1.75 mg by vein on Day -6.
Other Names:
  • ATG (Rabbit)
  • Rabbit Antithymocyte Globulin
  • Rabbit Antilymphocyte Globulin
  • rATG
  • Thymoglobulin

Radiation: Total Body Irradiation (TBI)

Treatment Plan #1: TBI 2 Gy in AM on Day -3.

Treatment Plan #2: TBI 2 Gy on Day -1.

Other Names:
  • Radiation Therapy
  • XRT

Procedure: Cord Blood Infusions
Cord blood infusions on Day 0.

Drug: Rituximab
375 mg/m2 by vein on Day -9 for participants with CD20+ malignancies.
Other Name: Rituxan

Drug: Cyclophosphamide
50 mg/kg by vein on Day -6.
Other Names:
  • Cytoxan
  • Neosar

Procedure: Natural Killer Cell Infusion
NK Cell Infusion (C2C2 subgroup only) on Day +30 to Day +80.

Drug: Mesna
Mesna by vein on Day -6, after cyclophosphamide to help lower the risk of side effects to the bladder.
Other Name: Mesnex

Experimental: Treatment Plan #3

Participants with AML, ALL, NHL, CLL, CML, and HD who are >/= 18 and </= 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy receive Reduced Intensity Regimen #3.

Participants receive fludarabine, ATG, and melphalan by vein.

Drug: Fludarabine

Treatment Plan #1: 10 mg/m2 by vein on Days -7 to -4. Participants </= 2 years of age receive Fludarabine 1.3 mg/kg.

Treatment Plan # 2: 40 mg/m2 by vein on Days -6 to -3.

Treatment Plan # 3: 40 mg/m2 by vein on Days -5 to -2.

Other Names:
  • Fludarabine phosphate
  • Fludara

Drug: Rabbit ATG
Treatment Plan # 1: 1.25 mg by vein on Day -9 and 1.75 mg by vein on Day -8. Treatment Plan # 2 1.25 mg by vein on Day -8 and 1.75 mg by vein on Day -7. Treatment Plan # 3: 1.25 mg by vein on Day -7 and 1.75 mg by vein on Day -6.
Other Names:
  • ATG (Rabbit)
  • Rabbit Antithymocyte Globulin
  • Rabbit Antilymphocyte Globulin
  • rATG
  • Thymoglobulin

Procedure: Cord Blood Infusions
Cord blood infusions on Day 0.

Procedure: Natural Killer Cell Infusion
NK Cell Infusion (C2C2 subgroup only) on Day +30 to Day +80.

Drug: Melphalan

140 mg/m2 by vein on Day -2.

For participants < 2 years of age: Melphalan 4.7 mg/kg.

Other Name: Alkeran




Primary Outcome Measures :
  1. Progression Free Survival (PFS) Time in C2C2 Participants [ Time Frame: Up to 2 years ]
    For the C2C2 participants, PFS time measured from the date that NK cells are given, i.e. from the date of engraftment. PFS time monitored by using the Bayesian method of Thrall et al.

  2. Progression Free Survival (PFS) Time in C1 Participants [ Time Frame: Up to 2 years ]
    For the C1 participants, PFS time measured from the date of cord blood transplant. PFS time monitored by using the Bayesian method of Thrall 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.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 including complex karyotype, abn(3q), -5/5q-, -7/7q-, abn(12p), abn(17p), MLL gene re-arrangement and t (6;9)47, flt3 mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from MDS, any disease beyond first remission.
  2. Myelodysplastic Syndrome (MDS): Primary or therapy related, including patients that will be considered for transplant. These include any of the following categories: 1) revised IPSS intermediate and high risk groups, 2) MDA with transfusion dependency, 3) failure to respond or progression of disease on hypomethylating agents, 4) refractory anemia with excess of blasts, 5) transformation to acute leukemia, 6) chronic myelomonocytic leukemia, 7) atypical MDS/myeloproliferative syndromes, 8) complex karyotype, abn(3g), -5/5g-, -7/7g-, abn(12p), abn(17p).
  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 translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease4 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). Relapsed double hit lymphomas. Patients with options for treatment that are known to be curative are not eligible.
  5. Small Lymphocytic Lymphoma (SLL), or Chronic lymphocytic Leukemia (CLL) with progressive disease following a minimum of two lines of standard therapy.
  6. CML second chronic phase or accelerated phase.
  7. Hodgkin's Disease (HD): Induction failures, after first complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant), or those with active disease.
  8. Multiple Myeloma: stage II or III, symptomatic, secretory Multiple Myeloma requiring treatment.
  9. A person (such as a haploidentical family member) or unit of cord blood must be identified as a source of back-up cells source in case of engraftment failure.
  10. Patient Age Criteria: Age >/= 18 and </= 45 years (Myeloablative Regimen 1. Age >/= 18 and </= 80 years (Nonmyeloablative Regimen 2) at the discretion of the investigator(s). Age >/= 18 and </= 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy may receive reduced intensity regimen 3.
  11. Performance score of at least 60% by Karnofsky
  12. Adequate major organ system function as demonstrated by: Left ventricular ejection fraction of at least 40% (Myeloablative Regimen 1, Reduced Intensity Regimen 3). Left ventricular ejection fraction of at least 30% (Nonmyeloablative Regimen 2).
  13. Pulmonary function test (PFT) demonstrating an adjusted diffusion capacity of least 50% predicted value for hemoglobin concentration (Myeloablative Regimen 1, Reduced Intensity Regimen 3).
  14. Serum creatinine within normal range, or if serum creatinine outside normal range, then renal function (measured or estimated creatinine clearance or GFR) > 40mL/min/1.73 m2.
  15. SGPT/bilirubin < to 2.0 x normal (Myeloablative Regimen 1), Reduced Intensity Regimen 3. SGPT/bilirubin < to 4.0 x normal (Nonmyeloablative Regimen 2).
  16. Negative Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months.
  17. Patients with options for treatment that are known to be curative are not eligible.

Exclusion Criteria:

  1. HIV positive. HIV results will be determined by nucleic acid testing
  2. Uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which CB transplantation is proposed), or psychiatric condition that would limit informed consent.
  3. Active CNS disease in patient with history of CNS malignancy.
  4. Availability of appropriate, willing, HLA-matched related stem cell donor.

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 ClinicalTrials.gov identifier (NCT number): NCT02727803


Contacts
Contact: Katy Rezvani, MD, PHD 713-792-8750
Contact: Clinical Research Operations UT MD Anderson CR_Study_Registration@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Cancer Prevention Research Institute of Texas
Investigators
Principal Investigator: Katy Rezvani, MD, PHD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02727803     History of Changes
Other Study ID Numbers: 2015-0313
NCI-2016-00584 ( Registry Identifier: NCI CTRP )
1R01CA211044-01 ( U.S. NIH Grant/Contract )
First Posted: April 5, 2016    Key Record Dates
Last Update Posted: June 25, 2018
Last Verified: June 2018

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:
Acute Myelogenous Leukemia
AML
Myelodysplastic syndrome
MDS
Multiple myeloma
MM
Umbilical cord blood transplant
UCB
Natural killer cells
NK
Busulfan
Busulfex
Myleran
Fludarabine
Fludarabine Phosphate
Fludara
Clofarabine
Clofarex
Clolar
Rabbit ATB
ATG (Rabbit)
Rabbit Antithymocyte Globulin
Rabbit Antilymphocyte Globulin
rATG Thymoglobulin
Total Body Irradiation
TBI
Radiation therapy
XRT
Rituximab
Rituxan

Additional relevant MeSH terms:
Bone Marrow Diseases
Myeloproliferative Disorders
Hematologic Diseases
Cyclophosphamide
Fludarabine phosphate
Melphalan
Busulfan
Thymoglobulin
Antilymphocyte Serum
Rituximab
Fludarabine
Clofarabine
Vidarabine
Mesna
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Protective Agents