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Umbilical Cord Blood NK Cells, Rituximab, High-Dose Chemotherapy, and Stem Cell Transplant in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma

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ClinicalTrials.gov Identifier: NCT03019640
Recruitment Status : Recruiting
First Posted : January 12, 2017
Last Update Posted : May 17, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies the side effects of cord blood-derived expanded allogeneic natural killer cells (umbilical cord blood natural killer [NK] cells), rituximab, high-dose chemotherapy, and stem cell transplant in treating patients with B-cell non-Hodgkin's lymphoma that has come back or that does not respond to treatment. Immune system cells, such as cord blood-derived expanded allogeneic natural killer cells, are made by the body to attack foreign or cancerous cells. Immunotherapy with rituximab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carmustine, cytarabine, etoposide, lenalidomide, melphalan, and rituximab, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. A stem cell transplant using stem cells from the patient or a donor may be able to replace blood-forming cells that were destroyed by chemotherapy used to kill cancer cells. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells. Giving cord blood-derived expanded allogeneic natural killer cells, rituximab, high-dose chemotherapy, and stem cell transplant may work better in treating patients with recurrent or refractory B-cell non-Hodgkin's lymphoma.

Condition or disease Intervention/treatment Phase
Mantle Cell Lymphoma Recurrent Diffuse Large B-Cell Lymphoma Recurrent Follicular Lymphoma Recurrent Indolent Adult Non-Hodgkin Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Follicular Lymphoma Refractory Indolent Adult Non-Hodgkin Lymphoma Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Carmustine Biological: Cord Blood-derived Expanded Allogeneic Natural Killer Cells Drug: Cytarabine Drug: Etoposide Biological: Filgrastim Drug: Lenalidomide Drug: Melphalan Biological: Rituximab Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To establish the safety of this treatment by determining its treatment-related mortality (TRM) within 30 days.

SECONDARY OBJECTIVES:

I. To estimate the relapse-free survival (RFS). II. To estimate the overall survival (OS). III. To quantify duration of infused allogeneic umbilical cord blood (UCB)-derived natural killer (NK) cells in the recipient.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive carmustine intravenously (IV) over 2 hours on day -12, etoposide IV twice daily (BID) over 3 hours on days -11 to -8, cytarabine IV BID over 1 hour on days -11 to -8, melphalan IV over 30 minutes on day -7, and lenalidomide orally (PO) once daily (QD) on days -7 to -2 in the absence of disease progression or unacceptable toxicity. Patients who are CD20+ also receive rituximab IV over 3 hours on days -13 and -7.

NK-CELL INFUSION: Patients receive cord blood-derived expanded allogeneic NK cells IV over 1 hour on day -5 in the absence of disease progression or unacceptable toxicity.

STEM CELL TRANSPLANT: Patients undergo stem cell transplant IV over 30-60 minutes on day 0 in the absence of disease progression or unacceptable toxicity.

POST-TRANSPLANT: Patients receive filgrastim subcutaneously (SC) QD beginning on day +5. Treatment continues until white blood cell count recovers in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30, 100, and 180 days.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Immunotherapy With Ex Vivo-Expanded Cord Blood-Derived NK Cells Combined With Rituximab High-Dose Chemotherapy and Autologous Stem Cell Transplant for B-Cell Non-Hodgkin's Lymphoma
Actual Study Start Date : October 10, 2017
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : March 31, 2020


Arm Intervention/treatment
Experimental: Treatment (chemotherapy, NK infusion, stem cell transplant)
See Detailed Description.
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo stem cell transplant
Other Names:
  • Autologous Hematopoietic Cell Transplantation
  • autologous stem cell transplantation

Drug: Carmustine
Given IV
Other Names:
  • BCNU
  • Becenum
  • Becenun
  • BiCNU
  • Bis(chloroethyl) Nitrosourea
  • Bis-Chloronitrosourea
  • Carmubris
  • Carmustin
  • Carmustinum
  • FDA 0345
  • Gliadel
  • N,N'-Bis(2-chloroethyl)-N-nitrosourea
  • Nitrourean
  • Nitrumon
  • SK 27702
  • SRI 1720
  • WR-139021

Biological: Cord Blood-derived Expanded Allogeneic Natural Killer Cells
Given IV
Other Names:
  • Allogeneic CB-derived Ex vivo-expanded NK Cells
  • CB-derived Expanded Allogeneic NK Cells
  • UCB-derived Expanded Allogeneic NK Cells
  • Umbilical Cord Blood-derived Expanded Allogeneic Natural Killer Cells

Drug: Cytarabine
Given IV
Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213

Biological: Filgrastim
Given SC
Other Names:
  • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
  • G-CSF
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tevagrastim

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

Drug: Melphalan
Given IV
Other Names:
  • Alanine Nitrogen Mustard
  • CB-3025
  • L-PAM
  • L-Phenylalanine Mustard
  • L-sarcolysin
  • L-Sarcolysin Phenylalanine mustard
  • L-Sarcolysine
  • Melphalanum
  • Phenylalanine Mustard
  • Phenylalanine nitrogen mustard
  • Sarcoclorin
  • Sarkolysin
  • WR-19813

Biological: Rituximab
Given IV
Other Names:
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • RTXM83




Primary Outcome Measures :
  1. Treatment-related mortality within 30 days (TRM30) [ Time Frame: Up to 30 days ]
    TRM30 will be estimated using a 95% credible interval assuming a beta(.50, .50) prior.


Secondary Outcome Measures :
  1. Relapse-free survival (RFS) [ Time Frame: From the time of transplant assessed up to progression or relapse, assessed up to 3 years ]
    Unadjusted RFS will be estimated by the method of Kaplan and Meier.

  2. Overall survival (OS) [ Time Frame: From the time of transplant, assessed up to 3 years ]
    Unadjusted OS will be estimated by the method of Kaplan and Meier.

  3. Natural killer (NK) cell persistence [ Time Frame: Up to 14 weeks ]
    A Bayesian hierarchical regression model will be fit to the longitudinal NK cell data to assess its patterns over time and association with patient covariates, including type of lymphoma, age, and disease severity.



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Ages Eligible for Study:   15 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with B-cell lymphoma who are candidates to autologous stem-cell transplantation:

    • Primary refractory or relapsed diffuse large B-cell lymphoma in response to salvage treatment
    • Primary refractory or relapsed follicular lymphoma or other indolent B-cell histology in response to salvage treatment
    • Chemosensitive mantle-cell lymphoma in first or later line of treatment
  • Adequate renal function, as defined by estimated serum creatinine clearance >= 60 ml/min and a normal serum creatinine for age
  • Serum glutamic-oxaloacetic transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit of normal (ULN)
  • Total bilirubin and alkaline phosphatase (ALP) =< 2 x ULN or =< 3 x ULN for Gilbert's disease
  • Adequate pulmonary function with forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and diffusion lung capacity (DLCO) (corrected for hemoglobin [Hgb]) >= 50% of the predicted value
  • Adequate cardiac function with left ventricular ejection fraction >= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease
  • Performance status < 2 (Eastern Cooperative Oncology Group [ECOG])
  • Negative beta human chorionic gonadotropin (HCG) in woman with child-bearing potential

Exclusion Criteria:

  • Primary central nervous system (CNS) lymphoma
  • Grade >= 3 non-hematologic toxicity from prior therapy that has not resolved to =< grade (G) 1
  • Prior whole brain irradiation
  • Active hepatitis B, either active carrier (hepatitis B surface antigen positive [HBsAg +]) or viremic (hepatitis B virus [HBV] deoxyribonucleic acid [DNA] >= 10,000 copies/mL, or >= 2,000 IU/mL)
  • Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology
  • Active infection requiring parenteral antibiotics
  • Human immunodeficiency virus (HIV) infection
  • Radiation therapy in the month prior to enroll
  • Breastfeeding females

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): NCT03019640


Contacts
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Contact: Yago Nieto 713-792-8750 ynieto@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Yago L. Nieto    713-792-8750      
Principal Investigator: Yago L. Nieto         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Yago L Nieto M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03019640     History of Changes
Other Study ID Numbers: 2015-0751
NCI-2018-01239 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2015-0751 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: January 12, 2017    Key Record Dates
Last Update Posted: May 17, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No

Additional relevant MeSH terms:
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Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Immunoglobulins
Rituximab
Lenalidomide
Antibodies, Monoclonal
Cytarabine
Melphalan
Lenograstim
Sargramostim
Antineoplastic Agents, Immunological
Etoposide
Carmustine
Mechlorethamine
Etoposide phosphate
Nitrogen Mustard Compounds
Podophyllotoxin
Immunologic Factors
Physiological Effects of Drugs