Mantle Cell LymphomaPhase 2NCT03019640
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
A Phase 2 study testing Autologous Hematopoietic Stem Cell Transplantation, Carmustine and Cord Blood-derived Expanded Allogeneic Natural Killer Cells in people with Mantle Cell Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 15 to 70 years
- Conditions the study is for
- Mantle Cell Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Follicular Lymphoma
- What is being tested?
- Autologous Hematopoietic Stem Cell Transplantation, Carmustine and Cord Blood-derived Expanded Allogeneic Natural Killer Cells
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Oct 2017to 16 Aug 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- Human immunodeficiency virus (HIV) infection
- Radiation therapy in the month prior to enroll
- Breastfeeding females
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To establish the safety of this treatment by determining its treatment-related mortality (TRM) within 30 days.
SECONDARY OBJECTIVES:
- 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.
- Conditions
- 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
- Being tested
- Autologous Hematopoietic Stem Cell Transplantation, Carmustine, Cord Blood-derived Expanded Allogeneic Natural Killer Cells, Cytarabine, Etoposide
- Medical subject headings
- Lymphoma, Mantle-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Autologous Hematopoietic Cell Transplantation, autologous stem cell transplantation
Undergo stem cell transplant
CarmustineDrug
Also called BCNU, Becenum, Becenun, BiCNU
Given IV
Cord Blood-derived Expanded Allogeneic Natural Killer CellsBiological
Also called 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
Given IV
CytarabineDrug
Also called .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
Given IV
EtoposideDrug
Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar
Given IV
FilgrastimBiological
Also called G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
Given SC
LenalidomideDrug
Also called CC-5013, CC5013, CDC 501, Revlimid
Given PO
MelphalanDrug
Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard
Given IV
RituximabBiological
Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (chemotherapy, NK infusion, stem cell transplant) | Experimental | See Detailed Description. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-related Mortality Within 30 Days (TRM30)
Participants that had Treatment-related mortality within 30 days.
Measured: Up to 30 days
Secondary outcomes (1)
Number of Participants Who Survived
Number of Participants Who Survived at day 180.
Measured: From the time of transplant, assessed up to day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2017 (estimated)
- Study start10 Oct 2017
- Primary completion16 Aug 2021
- Study completion16 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Mantle Cell LymphomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Yago L Nieto, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03019640
- Sponsor's protocol ID
- 2015-0751
- Other IDs
- NCI-2018-01239, 2015-0751
- Status last verified
- Dec 2022
- First submitted
- 11 Jan 2017
- Last updated
- 16 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03019640
- Acronym / sponsor ID
- 2015-0751
- Conditions
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 10 Oct 2017 (actual)
- Primary completion
- 16 Aug 2021 (actual)
- Study completion
- 16 Aug 2021 (actual)
- First posted
- 12 Jan 2017 (estimated)
- Results
- Posted 16 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To establish the safety of this treatment by determining its treatment-related mortality (TRM) within 30 days.
SECONDARY OBJECTIVES:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (chemotherapy, NK infusion, stem cell transplant) | Experimental | 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: RituximabSee Detailed Description. |
Who may qualify
- Ages
- 15 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with B-cell lymphoma who are candidates to autologous stem-cell transplantation:
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous Hematopoietic Stem Cell TransplantationAlso: Autologous Hematopoietic Cell Transplantation, autologous stem cell transplantationUndergo stem cell transplant | Procedure or surgery | Treatment (chemotherapy, NK infusion, stem cell transplant) |
| CarmustineAlso: BCNU, Becenum, Becenun, BiCNUGiven IV | Drug | Treatment (chemotherapy, NK infusion, stem cell transplant) |
| Cord Blood-derived Expanded Allogeneic Natural Killer CellsAlso: 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 CellsGiven IV | Biological | Treatment (chemotherapy, NK infusion, stem cell transplant) |
| CytarabineAlso: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinoneGiven IV | Drug | Treatment (chemotherapy, NK infusion, stem cell transplant) |
| EtoposideAlso: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, ToposarGiven IV | Drug | Treatment (chemotherapy, NK infusion, stem cell transplant) |
| FilgrastimAlso: G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating FactorGiven SC | Biological | Treatment (chemotherapy, NK infusion, stem cell transplant) |
| LenalidomideAlso: CC-5013, CC5013, CDC 501, RevlimidGiven PO | Drug | Treatment (chemotherapy, NK infusion, stem cell transplant) |
| MelphalanAlso: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine MustardGiven IV | Drug | Treatment (chemotherapy, NK infusion, stem cell transplant) |
| RituximabAlso: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 AntibodyGiven IV | Biological | Treatment (chemotherapy, NK infusion, stem cell transplant) |
Primary outcome
Treatment-related Mortality Within 30 Days (TRM30)
Time frame: Up to 30 days
Participants that had Treatment-related mortality within 30 days.
1 secondary outcome
Number of Participants Who Survived
Time frame: From the time of transplant, assessed up to day 180
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yago L Nieto principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Autologous Hematopoietic Stem Cell Transplantation, Carmustine and Cord Blood-derived Expanded Allogeneic Natural Killer Cells in people with Mantle Cell Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-related Mortality Within 30 Days (TRM30) (time frame: Up to 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2023.