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Cord Blood Natural Killer (NK) Cells in Leukemia/Lymphoma

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ClinicalTrials.gov Identifier: NCT02280525
Recruitment Status : Active, not recruiting
First Posted : October 31, 2014
Last Update Posted : November 29, 2018
Sponsor:
Collaborators:
The Leukemia and Lymphoma Society
Celgene Corporation
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the highest tolerable dose of immune cells called natural killer (NK) cells that can be given with chemotherapy to patients with CLL. Researchers want to learn if adding NK cells will be effective in treating the disease. The safety of this will also be studied.

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.

This is an investigational study. Rituximab, fludarabine, and cyclophosphamide are FDA approved and commercially available for the treatment of CLL. Cytarabine, filgrastim, and lenalidomide are FDA approved and commercially available for the treatment of other types of cancer. The use of cytarabine, filgrastim, and lenalidomide for the treatment of CLL is investigational.

The use of NK cells is investigational. The NK cell process is not FDA approved or commercially available. It is currently being used for research purposes only.

Up to 44 patients will take part in this study. All will be enrolled at MD Anderson.


Condition or disease Intervention/treatment Phase
Leukemia Drug: Lenalidomide Drug: Rituximab Drug: Fludarabine Drug: Cyclophosphamide Procedure: NK Cells Drug: Cytarabine Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study of Umbilical Cord Blood-Derived Natural Killer Cells in Conjunction With Lymphodepleting Chemotherapy and Lenalidomide as Immunotherapy in Patients With Hematologic Malignancies
Actual Study Start Date : March 5, 2015
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021


Arm Intervention/treatment
Experimental: Lymphodepleting Chemotherapy Option #1

Preferred regimen for CLL and low grade lymphoma

Lenalidomide 2.5 mg by mouth once a day on Days -2 through Day +14. Fludarabine 25 mg/m2 by vein over 1 hour on Days -5 to -3. Cyclophosphamide 200 mg/m2 by vein over 3 hours on Days -5 to -3. Rituximab 375 mg/m2 by vein over 3-6 hours on Day -5 for participants with B-cell cancer.

Dose Escalation Phase Starting Dose Level of NK Cells: 1 x 10^7 NK cells/kg given by vein on Day 0.

Dose Expansion Phase Starting Dose level of NK cells: Maximum tolerated dose from Dose Escalation Phase.

Drug: Lenalidomide
2.5 mg by mouth daily on Day -2 to Day +14.
Other Names:
  • CC-5013
  • Revlimid

Drug: Rituximab
375 mg/m2 by vein on Day -5 for participants with B-cell cancer.
Other Name: Rituxan

Drug: Fludarabine

Lymphodepleting Chemotherapy Option #1: Fludarabine 25 mg/m2 by vein on Days -5 to -3.

Lymphodepleting Chemotherapy Option #2: Fludarabine 25 mg/m2 by vein over 1 hour on Day -6 to -2.

Lymphodepleting Chemotherapy Option #3: Fludarabine 30 mg/m2 by vein over 1 hour on Days -6 to -2

Other Names:
  • Fludarabine Phosphate
  • Fludara

Drug: Cyclophosphamide

Lymphodepleting Chemotherapy Option #1: Cyclophosphamide 200 mg/m2 by vein on Days -5 to -3.

Lymphodepleting Chemotherapy Option #2: Cyclophosphamide 60 mg/kg by vein over 3 hours on Days -5 and -4.

Other Names:
  • Cytoxan
  • Neosar

Procedure: NK Cells

Participant assigned to a dose level of NK cells based on when joined study. Starting dose level of NK cells 1 x 10^7 NK cells/kg given by vein on Day 0.

NK Cell Infusion Expansion Phase: Maximum tolerated dose of NK cells from Induction Phase.


Experimental: Lymphodepleting Chemotherapy Option #2

For all malignancies if able to tolerate higher dose cyclophosphamide per the discretion of the treating physician

Lenalidomide 2.5 mg by mouth once a day on Days -2 through Day +14. Fludarabine 25 mg/m2 by vein over 1 hour on Day -6 to -2. Cyclophosphamide 60 mg/kg by vein over 3 hours on Days -5 and -4.

Dose Escalation Phase Starting Dose Level of NK Cells: 1 x 10^7 NK cells/kg given by vein on Day 0.

Dose Expansion Phase Starting Dose level of NK cells: Maximum tolerated dose from Dose Escalation Phase.

Drug: Lenalidomide
2.5 mg by mouth daily on Day -2 to Day +14.
Other Names:
  • CC-5013
  • Revlimid

Drug: Fludarabine

Lymphodepleting Chemotherapy Option #1: Fludarabine 25 mg/m2 by vein on Days -5 to -3.

Lymphodepleting Chemotherapy Option #2: Fludarabine 25 mg/m2 by vein over 1 hour on Day -6 to -2.

Lymphodepleting Chemotherapy Option #3: Fludarabine 30 mg/m2 by vein over 1 hour on Days -6 to -2

Other Names:
  • Fludarabine Phosphate
  • Fludara

Drug: Cyclophosphamide

Lymphodepleting Chemotherapy Option #1: Cyclophosphamide 200 mg/m2 by vein on Days -5 to -3.

Lymphodepleting Chemotherapy Option #2: Cyclophosphamide 60 mg/kg by vein over 3 hours on Days -5 and -4.

Other Names:
  • Cytoxan
  • Neosar

Procedure: NK Cells

Participant assigned to a dose level of NK cells based on when joined study. Starting dose level of NK cells 1 x 10^7 NK cells/kg given by vein on Day 0.

NK Cell Infusion Expansion Phase: Maximum tolerated dose of NK cells from Induction Phase.


Experimental: Lymphodepleting Chemotherapy Option #3

For myeloid malignancies

Lenalidomide 2.5 mg by mouth once a day on Days -2 to Day +14. Fludarabine 30 mg/m2 by vein over 1 hour on Days -6 to -2. Cytarabine 2 mg/m2 by vein on Days -6 to -2.

Dose Escalation Phase Starting Dose Level of NK Cells: 1 x 10^7 NK cells/kg given by vein on Day 0.

Dose Expansion Phase Starting Dose level of NK cells: Maximum tolerated dose from Dose Escalation Phase.

Drug: Lenalidomide
2.5 mg by mouth daily on Day -2 to Day +14.
Other Names:
  • CC-5013
  • Revlimid

Drug: Fludarabine

Lymphodepleting Chemotherapy Option #1: Fludarabine 25 mg/m2 by vein on Days -5 to -3.

Lymphodepleting Chemotherapy Option #2: Fludarabine 25 mg/m2 by vein over 1 hour on Day -6 to -2.

Lymphodepleting Chemotherapy Option #3: Fludarabine 30 mg/m2 by vein over 1 hour on Days -6 to -2

Other Names:
  • Fludarabine Phosphate
  • Fludara

Procedure: NK Cells

Participant assigned to a dose level of NK cells based on when joined study. Starting dose level of NK cells 1 x 10^7 NK cells/kg given by vein on Day 0.

NK Cell Infusion Expansion Phase: Maximum tolerated dose of NK cells from Induction Phase.


Drug: Cytarabine
Cytarabine 2 mg/m2 by vein on Days -6 to -2.
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Natural Killer (NK) Cells with Lenalidomide and Lymphodepleting Chemotherapy [ Time Frame: 30 days ]
    Primary objective is to determine maximum tolerated dose (MTD). Dose-limiting toxicity (DLT) target rate is at most 20%. DLT includes any grade 4 toxicity related to NK infusion related toxicity; grades 3-5 allergic reactions related to study cell infusion; grades 3-5 organ toxicity (cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic) not pre-existing or due to underlying malignancy or due to preparative chemotherapy and occurring within 30 days post-NK infusion.


Secondary Outcome Measures :
  1. Response Rate of Natural Killer (NK) Cells with Lenalidomide and Lymphodepleting Chemotherapy Determined by Bone Marrow Biopsy/Aspiration [ Time Frame: 1 week, 3 weeks, 1 month, and 4 months after the NK cell infusion ]


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 with history of hematologic malignancies who have received at least 2 lines of standard chemoimmunotherapy and have persistent disease.
  2. Patients with acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) with relapsed or refractory disease who are not eligible for stem cell transplantation or other standard therapies.
  3. Patients with histologically confirmed aggressive hematologic malignancies with chemotherapy-refractory disease. Chemotherapy refractory disease is defined as one or more of the following: Stable disease or progressive disease as best response to most recent chemotherapy containing regimen or disease progression or recurrence within 12 months of prior Autologous or allogeneic stem cell transplant. Subjects must have received adequate prior therapy including at a minimum: anti-CD20 monoclonal antibody unless tumor is CD20-negative, an anthracycline containing chemotherapy regimen. Subjects with transformed FL must have received prior chemotherapy for follicular lymphoma and subsequently have chemo-refractory disease after transformation to diffuse large B-cell lymphoma (DLBCL).
  4. Patient with Hodgkin's Lymphoma with relapsed or refractory disease who are not eligible for stem cell transplantation or other standard therapies.
  5. Patients at least 3 weeks from last cytotoxic chemotherapy. Patients may continue tyrosine kinase inhibitors and/or lenalidomide until the day of study consent.
  6. Karnofsky Performance Scale > 60%.
  7. Adequate hepatic function, as defined by SGPT <3 X upper limit of normal; serum bilirubin and alkaline phosphatase <2 X upper limit of normal, or considered not clinically significant by the study doctor or designee, serum creatinine of </=2 mg/dl.
  8. Able to provide written informed consent.
  9. 18-80 years of age.
  10. All study participants must be registered into the mandatory Revlimid REMSTM program, and be willing and able to comply with the requirements of the Revlimid REMSTM program. Females of childbearing potential must adhere to the scheduled pregnancy testing and contraception as required in the Revlimid REMSTM program. A female of childbearing potential (FCBP) is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  11. 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.
  12. Patients must have a CB unit available which is matched with the patient at 3, 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens.
  13. Patients who are HIV positive must be willing to comply with effective antiretroviral therapy.

Exclusion Criteria:

  1. Positive beta HCG in female of child-bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females.
  2. Presence of Grade 3 or greater toxicity from the previous treatment.
  3. Concomitant use of other investigational agents.
  4. Not consenting to participate in LAB00-099.
  5. Patients with known hypersensitivity to lenalidomide and/or rituximab (CD20+ patients only).
  6. Patients who are HIV positive with a detectable viral load > 750 copies/ml on adequate retroviral therapy must be evaluated for HIV drug resistance test (HIV-1 genotype). These patients may be enrolled only after discussion with the PI and the Infectious Disease team.

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): NCT02280525


Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
The Leukemia and Lymphoma Society
Celgene Corporation
Investigators
Principal Investigator: Chitra M. Hosing, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02280525     History of Changes
Other Study ID Numbers: 2014-0297
P-TRP-1996-14 ( Other Grant/Funding Number: Leukemia & Lymphoma Society (LLS) )
NCI-2014-02678 ( Registry Identifier: NCI CTRP )
First Posted: October 31, 2014    Key Record Dates
Last Update Posted: November 29, 2018
Last Verified: November 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:
Leukemia
Chronic Lymphocytic Leukemia
CLL
Natural Killer Cells
NK
Umbilical Cord Blood
UCB
Lenalidomide
CC-5013
Revlimid
Rituximab
Rituxan
Fludarabine
Fludarabine phosphate
Fludara
Cyclophosphamide
Cytoxan
Neosar
Cytarabine
Ara-C
Cytosar
DepoCyt
Cytosine Arabinosine Hydrochloride

Additional relevant MeSH terms:
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Thalidomide
Fludarabine phosphate
Cytarabine
Rituximab
Lenalidomide
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents