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

NCT02280525 | Completed Phase 1 FDA Drug

• 3 other identifiers: 2014-0297P-TRP-1996-14NCI-2014-02678
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Natural Killer (NK) Cells with Lenalidomide and Lymphodepleting Chemotherapy

  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.

  30 days

Secondary Outcomes (1)

• Response Rate of Natural Killer (NK) Cells with Lenalidomide and Lymphodepleting Chemotherapy Determined by Bone Marrow Biopsy/Aspiration

  1 week, 3 weeks, 1 month, and 4 months after the NK cell infusion

Study Arms (3)

Lymphodepleting Chemotherapy Option #1

EXPERIMENTAL

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; Drug: Rituximab; Drug: Fludarabine; Drug: Cyclophosphamide; Procedure: NK Cells

Lymphodepleting Chemotherapy Option #2

EXPERIMENTAL

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; Drug: Fludarabine; Drug: Cyclophosphamide; Procedure: NK Cells

Lymphodepleting Chemotherapy Option #3

EXPERIMENTAL

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; Drug: Fludarabine; Procedure: NK Cells; Drug: Cytarabine

Interventions

Lenalidomide DRUG

2.5 mg by mouth daily on Day -2 to Day +14.

Also known as: CC-5013, Revlimid

Lymphodepleting Chemotherapy Option #1; Lymphodepleting Chemotherapy Option #2; Lymphodepleting Chemotherapy Option #3

Rituximab DRUG

375 mg/m2 by vein on Day -5 for participants with B-cell cancer.

Also known as: Rituxan

Lymphodepleting Chemotherapy Option #1

Fludarabine DRUG

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

Also known as: Fludarabine Phosphate, Fludara

Lymphodepleting Chemotherapy Option #1; Lymphodepleting Chemotherapy Option #2; Lymphodepleting Chemotherapy Option #3

Cyclophosphamide DRUG

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.

Also known as: Cytoxan, Neosar

Lymphodepleting Chemotherapy Option #1; Lymphodepleting Chemotherapy Option #2

NK Cells PROCEDURE

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.

Lymphodepleting Chemotherapy Option #1; Lymphodepleting Chemotherapy Option #2; Lymphodepleting Chemotherapy Option #3

Cytarabine DRUG

Cytarabine 2 mg/m2 by vein on Days -6 to -2.

Also known as: Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride

Lymphodepleting Chemotherapy Option #3

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with history of hematologic malignancies who have received at least 2 lines of standard chemoimmunotherapy and have persistent disease.
• 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.
• 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).
• Patient with Hodgkin's Lymphoma with relapsed or refractory disease who are not eligible for stem cell transplantation or other standard therapies.
• Patients at least 3 weeks from last cytotoxic chemotherapy. Patients may continue tyrosine kinase inhibitors and/or lenalidomide until the day of study consent.
• Karnofsky Performance Scale \> 60%.
• 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.
• Able to provide written informed consent.
• years of age.
• 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).
• 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.
• 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.
• Patients who are HIV positive must be willing to comply with effective antiretroviral therapy.

You may not qualify if:

• Positive beta HCG in female of child-bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females.
• Presence of Grade 3 or greater toxicity from the previous treatment.
• Concomitant use of other investigational agents.
• Not consenting to participate in LAB00-099.
• Patients with known hypersensitivity to lenalidomide and/or rituximab (CD20+ patients only).
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• The Leukemia and Lymphoma Society: collaborator
• Celgene Corporation: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Lenalidomide; Rituximab; fludarabine; fludarabine phosphate; Cyclophosphamide; Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Chitra M. Hosing, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2014
• First Posted: October 31, 2014
• Study Start: March 5, 2015
• Primary Completion: July 9, 2019
• Study Completion: July 9, 2019
• Last Updated: June 7, 2023

Record last verified: 2023-06

Locations

US (1)