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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

Primary Purpose

Mantle Cell Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Follicular Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Autologous Hematopoietic Stem Cell Transplantation
Carmustine
Cord Blood-derived Expanded Allogeneic Natural Killer Cells
Cytarabine
Etoposide
Filgrastim
Lenalidomide
Melphalan
Rituximab
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mantle Cell Lymphoma

Eligibility Criteria

15 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemotherapy, NK infusion, stem cell transplant)

Arm Description

See Detailed Description.

Outcomes

Primary Outcome Measures

Treatment-related Mortality Within 30 Days (TRM30)
Participants that had Treatment-related mortality within 30 days.

Secondary Outcome Measures

Number of Participants Who Survived
Number of Participants Who Survived at day 180.

Full Information

First Posted
January 11, 2017
Last Updated
February 15, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03019640
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
October 10, 2017 (Actual)
Primary Completion Date
August 16, 2021 (Actual)
Study Completion Date
August 16, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemotherapy, NK infusion, stem cell transplant)
Arm Type
Experimental
Arm Description
See Detailed Description.
Intervention Type
Procedure
Intervention Name(s)
Autologous Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
Autologous Hematopoietic Cell Transplantation, autologous stem cell transplantation
Intervention Description
Undergo stem cell transplant
Intervention Type
Drug
Intervention Name(s)
Carmustine
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Cord Blood-derived Expanded Allogeneic Natural Killer Cells
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
.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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
CC-5013, CC5013, CDC 501, Revlimid
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
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
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Treatment-related Mortality Within 30 Days (TRM30)
Description
Participants that had Treatment-related mortality within 30 days.
Time Frame
Up to 30 days
Secondary Outcome Measure Information:
Title
Number of Participants Who Survived
Description
Number of Participants Who Survived at day 180.
Time Frame
From the time of transplant, assessed up to day 180

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yago L Nieto
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website

Learn more about this trial

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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