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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03019640
Recruitment Status : Recruiting
First Posted : January 12, 2017
Last Update Posted : October 2, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE January 11, 2017
First Posted Date  ICMJE January 12, 2017
Last Update Posted Date October 2, 2019
Actual Study Start Date  ICMJE October 10, 2017
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 11, 2017)
Treatment-related mortality (TRM) within 30 days [ Time Frame: 30 days ]
Number of participants with transplant related mortality within 30 days.
Change History Complete list of historical versions of study NCT03019640 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2017)
  • Relapse-free survival (RFS) [ Time Frame: 1 year ]
    RFS will be defined as the time from transplant to either progression/relapse or death, whichever occurs first, or last contact
  • Overall survival (OS) [ Time Frame: 2 years ]
    OS will be defined as the time from transplant to death or last contact.
  • NK Cell Persistence: Duration of infused Allo UCB-derived NK cells [ Time Frame: 14 weeks ]
    NK cell persistence: In order to quantify duration of infused allogeneic umbilical cord blood (UCB)-derived natural killer (NK) cells in the recipient, NK cells measured weekly for 14 weeks
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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 (recurrent) or that does not respond to treatment (refractory). 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.
Detailed Description

PRIMARY OBJECTIVE:

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
    • 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
    • VP 16-213
    • VP-16
    • VP-16-213
    • VP16
  • Biological: Filgrastim
    Given SC
    Other Names:
    • 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 ABBS
    • Rituximab Biosimilar ABP 798
    • Rituximab Biosimilar BI 695500
    • Rituximab Biosimilar CT-P10
    • Rituximab Biosimilar GB241
    • Rituximab Biosimilar IBI301
    • Rituximab Biosimilar JHL1101
    • Rituximab Biosimilar PF-05280586
    • Rituximab Biosimilar RTXM83
    • Rituximab Biosimilar SAIT101
    • rituximab biosimilar TQB2303
    • rituximab-abbs
    • RTXM83
    • Truxima
Study Arms  ICMJE Experimental: Treatment (chemotherapy, NK infusion, stem cell transplant)
See Detailed Description.
Interventions:
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 11, 2017)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2020
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • 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
  • 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yago Nieto 713-792-8750 ynieto@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03019640
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Yago L Nieto M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP