LymphomaNCT02652468
TCR-α/β and CD19 Depleted Stem Cell Grafts From Haplo Donors for HSCT in Relapsed Lymphoma
A study testing Fludarabine Phosphate, Mesna and Cyclophosphamide in people with Lymphoma, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
To determine engraftment of neutrophils and platelets at 28 days following alpha/beta T-cell and CD19 cell depletion using Human Leukocyte Antigen (HLA) haploidentical donors for peripheral blood stem cell transplant in relapsed lymphoma. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Lymphoma
- What is being tested?
- Fludarabine Phosphate, Mesna and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Mar 2016to 17 Sep 2021
- Phase
- Interventional
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must meet one of the following disease criteria within 24 months of registration. Salvage therapy is allowed between the participant meeting one of the below criterion and registration. Participant will be considered eligible regardless of their current disease status (i.e. complete remission, partial remission, stable disease, progressive disease) unless otherwise noted below as long as one of the below criterion has been met within the previous 24 months:
- Relapsed/refractory Hodgkin lymphoma after autologous stem cell transplantation
- Relapsed/refractory Hodgkin lymphoma, deemed ineligible for autologous stem cell transplantation due to refractory disease
- Relapsed/refractory diffuse large B cell lymphoma after autologous stem cell transplantation (history of transformed lymphoma is acceptable). Disease must be in at least complete remission or partial remission with the use of salvage therapy before study treatment commences.
- Relapsed/refractory diffuse large B cell lymphoma, deemed ineligible for autologous stem cell transplantation due to refractory disease (history of transformed lymphoma is acceptable). Disease must be in at least complete remission or partial remission with the use of salvage therapy before study treatment commences.
- Relapsed/refractory T cell lymphoma relapsed after at least 1 prior line of therapy
Show all 16Show fewer
- Relapsed/refractory follicular lymphoma relapsed after at least 1 prior line of therapy
- Relapsed/refractory mantle cell lymphoma relapsed after at least 1 prior line of therapy
- Relapsed/refractory small lymphocytic lymphoma/chronic lymphocytic leukemia relapsed after at least 1 prior line of therapy
- Relapsed/refractory non-Hodgkin Lymphoma, if not specified above, relapsed after at least 1 prior line of therapy
- Karnofsky score of 60% or better ("Requires occasional assistance, but is able to care for most of his/her needs").
- Pulmonary: Carbon Monoxide Diffusion Capacity (DLCO) (corrected for hemoglobin) > 40%; and Forced Expiratory Volume (FEV1) > 50%
- Cardiac: ejection fraction (EF) ≥ 50%. No uncontrolled angina or active cardiac symptoms consistent with congestive heart failure (class III or IV), by the New York Heart Association criteria. No symptomatic ventricular arrhythmias or ECG evidence of active ischemia. No evidence by echocardiography of severe valvular stenosis or regurgitation.
- Renal: estimated glomerular filtration rate (GFR) by Modification of Diet in Renal Disease (MDRD) formula > 40 mL/min/1.73m2
- Women of child bearing potential must have a negative serum or urine pregnancy test within 14 days prior to study registration and agree to use adequate birth control during study treatment. 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).
- Voluntary written consent
Who cannot join
- Active Central nervous system (CNS) lymphoma within two weeks of registration. Patients with a history of CNS involvement must have adequate treatment as defined by at least two negative spinal fluid assessments separated by at least one week. (Otherwise Lumbar Puncture (LP) is not required if no clinical suspicion or evidence of CNS involvement.) Patients who have received cranial radiation therapy must still be eligible to receive total lymphoid irradiation to 7 Gy.
- New or active infection as determined by fever, unexplained pulmonary infiltrate or sinusitis on radiographic assessment. Infections diagnosed within 4 weeks of registration must be determined to be controlled or resolving prior to treatment.
- Presence of HIV, or active hepatitis A, B, or C infection
- Allergy or hypersensitivity to agents used within the treatment protocol.
- For an indolent lymphoma histology (follicular lymphoma, Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia (SLL/CLL)) or mantle cell lymphoma, the patient should not have an HLA-matched sibling, who would be an eligible donor, available.
- History of prior mediastinal radiation
- Reported illicit drug use
- Vulnerable population groups, i.e., prisoners, those lacking consent capacity, non-English speaking, illiterate, pregnant females.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53705
About this study
Official title: A Pilot Study to Assess Engraftment Using CliniMACS TCR-α/β and CD19 Depleted Stem Cell Grafts From Haploidentical Donors for Hematopoietic Progenitor Cell Transplantation (HSCT) in Patients With Relapsed Lymphoma
To determine engraftment of neutrophils and platelets at 28 days following alpha/beta T-cell and CD19 cell depletion using Human Leukocyte Antigen (HLA) haploidentical donors for peripheral blood stem cell transplant in relapsed lymphoma.
Assess incidence of acute Graft Versus Host Disease (GVHD), chronic GVHD, graft failure rate, treatment related mortality rate, progression free survival and overall survival of patients.
The stem cell product will be processed using an investigational Miltenyi cell selection device/system that removes the alpha/beta T-cells and CD19+ cells, immune system cells that are more likely to cause GVHD.
- Conditions
- Lymphoma
- Being tested
- Fludarabine Phosphate, Mesna, Cyclophosphamide, Total nodal irradiation, T Cell-Depleted Hematopoietic Stem Cell Transplantation
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fludarabine will be administered by IV over approximately 30 minutes for 4 days.
MesnaDrug
Given IV over 24 hours starting prior to cyclophosphamide
CyclophosphamideDrug
Given IV for 2 days
Total nodal irradiationRadiation
Undergo total lymphoid irradiation
T Cell-Depleted Hematopoietic Stem Cell TransplantationBiological
Undergo TCR alpha-beta/DC19-depleted hematopoietic stem cell transplant
Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called HSC, HSCT
Undergo TCR alpha-beta/DC19-depleted hematopoietic stem cell transplant
Peripheral Blood Stem Cell TransplantationProcedure or surgery
Undergo TCR alpha-beta/CD19-depleted hematopoietic stem cell transplant
Also called MMF
Given PO
TacrolimusDrug
Given PO or IV ONLY if graft cell content is over 1 x 10^5 cells/kg ideal BW of the patient
RituximabBiological
Given IV ONLY if graft B cell content exceeds 1 x 10^5 cells/kg ideal BW of the patient
| Study group | Role | What they receive |
|---|---|---|
| Peripheral Blood Stem Cell Transplant | Experimental | PREPARATIVE REGIMEN: Participants receive fludarabine phosphate IV over approximately 30 minutes on days -5 to -2, and mesna IV over 24 hours and cyclophosphamide IV over approximately 2 hours on days -5 and -4. Participants also undergo total nodal irradiation on day -1.
TRANSPLANT: Participants undergo T-Cell Receptor (TCR) alpha-beta/CD19 depleted hematopoietic stem cell transplant on day 0. If the graft contains less than 4 x 10^6 CD34+ cells/kg participant body weight (BW), patients may receive a second graft on day 1.
GVHD PROPHYLAXIS: Participants receive mycophenolate mofetil orally twice a day (PO BID) on days -1 to 30, tacrolimus PO or IV on days 2-180 with a taper beginning on day 90 (given only if graft TCR alpha-beta+ cell content is over 1 x 10^5 cells/kg ideal BW of the patient), and rituximab IV on day 2 (given only if graft B cell content exceeds 1 x 10^5 cells/kg ideal BW of the participant). Receives: Drug: Fludarabine Phosphate; Drug: Mesna; Drug: Cyclophosphamide; Radiation: Total nodal irradiation; Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Biological: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Absolute Neutrophil Count >= 500/Mcl for 3 Consecutive Measurements on Different Days and Platelet Count > 20,000/mm^3 With no Platelet Transfusions in the Preceding 7 Days
To determine engraftment of neutrophils and platelets at 28 days following alpha/beta T-cell depletion using Human Leukocyte Antigen (HLA) haploidentical donors for stem cell transplant in relapsed lymphoma.
Measured: At day 28 after transplantation
Secondary outcomes (6)
Number of Participants With Grade III-IV Acute GVHD as Determined by International Bone Marrow Transplant Registry (IBMTR) Severity Index Criteria
The number of participants with grade III - IV acute Graft versus host disease (GVHD) by Day +100 is reported.
Measured: Day +100
Number of Participants With Severe Chronic GVHD
The number of participants with severe chronic GVHD by Day +180 will be reported.
Measured: Day +180
Number of Participants With Graft Failure
Graft failure - defined as < 5% donor chimerism in the CD3 and/or CD33 selected cell populations at any time during the study follow up period once initial engraftment has been achieved.
Measured: Up to 2 years after graft
Number of Participants With Treatment-related Mortality
Treatment-related mortality is defined as death from any cause other than disease progression.
Measured: Up to 2 years after graft
Progression-free Survival
Progression-free survival will be analyzed as time before any progression by either Positron Emission Tomography/Computed Tomography (PET/CT) or bone marrow,
Measured: Median follow up of 1689 days
Overall Survival (OS)
Measured: Median follow up of 1689 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2016 (estimated)
- Study start10 Mar 2016
- Primary completion1 Sep 2018
- Study completion17 Sep 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 LymphomaStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vaishalee P Kenkre, Principal investigator, Principal Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02652468
- Sponsor's protocol ID
- UW14113
- Other IDs
- 2015-0996, NCI-2015-02269, A534260, SMPH\MEDICINE\HEM-ONC, Protocol Version 4/24/2020
- Status last verified
- Dec 2021
- First submitted
- 5 Jan 2016
- Last updated
- 5 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Assess Engraftment Using CliniMACS TCR-α/β and CD19 Depleted Stem Cell Grafts From Haploidentical Donors for Hematopoietic Progenitor Cell Transplantation (HSCT) in Patients With Relapsed Lymphoma
- ClinicalTrials.gov ID
- NCT02652468
- Acronym / sponsor ID
- UW14113
- Conditions
- Lymphoma
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Study start
- 10 Mar 2016 (actual)
- Primary completion
- 1 Sep 2018 (actual)
- Study completion
- 17 Sep 2021 (actual)
- First posted
- 11 Jan 2016 (estimated)
- Results
- Posted 13 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine engraftment of neutrophils and platelets at 28 days following alpha/beta T-cell and CD19 cell depletion using Human Leukocyte Antigen (HLA) haploidentical donors for peripheral blood stem cell transplant in relapsed lymphoma.
Assess incidence of acute Graft Versus Host Disease (GVHD), chronic GVHD, graft failure rate, treatment related mortality rate, progression free survival and overall survival of patients.
The stem cell product will be processed using an investigational Miltenyi cell selection device/system that removes the alpha/beta T-cells and CD19+ cells, immune system cells that are more likely to cause GVHD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Peripheral Blood Stem Cell Transplant | Experimental | Drug: Fludarabine Phosphate, Drug: Mesna, Drug: Cyclophosphamide, Radiation: Total nodal irradiation, Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation, Procedure: Allogeneic Hematopoietic Stem Cell Transplantation, Procedure: Peripheral Blood Stem Cell Transplantation, Drug: Mycophenolate Mofetil, Drug: Tacrolimus, Biological: RituximabPREPARATIVE REGIMEN: Participants receive fludarabine phosphate IV over approximately 30 minutes on days -5 to -2, and mesna IV over 24 hours and cyclophosphamide IV over approximately 2 hours on days -5 and -4. Participants also undergo total nodal irradiation on day -1. TRANSPLANT: Participants undergo T-Cell Receptor (TCR) alpha-beta/CD19 depleted hematopoietic stem cell transplant on day 0. If the graft contains less than 4 x 10^6 CD34+ cells/kg participant body weight (BW), patients may receive a second graft on day 1. GVHD PROPHYLAXIS: Participants receive mycophenolate mofetil orally twice a day (PO BID) on days -1 to 30, tacrolimus PO or IV on days 2-180 with a taper beginning on day 90 (given only if graft TCR alpha-beta+ cell content is over 1 x 10^5 cells/kg ideal BW of the patient), and rituximab IV on day 2 (given only if graft B cell content exceeds 1 x 10^5 cells/kg ideal BW of the participant). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Participants must meet one of the following disease criteria within 24 months of registration. Salvage therapy is allowed between the participant meeting one of the below criterion and registration. Participant will be considered eligible regardless of their current disease status (i.e. complete remission, partial remission, stable disease, progressive disease) unless otherwise noted below as long as one of the below criterion has been met within the previous 24 months:
- Karnofsky score of 60% or better ("Requires occasional assistance, but is able to care for most of his/her needs").
- Pulmonary: Carbon Monoxide Diffusion Capacity (DLCO) (corrected for hemoglobin) > 40%; and Forced Expiratory Volume (FEV1) > 50%
- Cardiac: ejection fraction (EF) ≥ 50%. No uncontrolled angina or active cardiac symptoms consistent with congestive heart failure (class III or IV), by the New York Heart Association criteria. No symptomatic ventricular arrhythmias or ECG evidence of active ischemia. No evidence by echocardiography of severe valvular stenosis or regurgitation.
- Renal: estimated glomerular filtration rate (GFR) by Modification of Diet in Renal Disease (MDRD) formula > 40 mL/min/1.73m2
Key exclusion criteria (8 listed)
- Active Central nervous system (CNS) lymphoma within two weeks of registration. Patients with a history of CNS involvement must have adequate treatment as defined by at least two negative spinal fluid assessments separated by at least one week. (Otherwise Lumbar Puncture (LP) is not required if no clinical suspicion or evidence of CNS involvement.) Patients who have received cranial radiation therapy must still be eligible to receive total lymphoid irradiation to 7 Gy.
- New or active infection as determined by fever, unexplained pulmonary infiltrate or sinusitis on radiographic assessment. Infections diagnosed within 4 weeks of registration must be determined to be controlled or resolving prior to treatment.
- Presence of HIV, or active hepatitis A, B, or C infection
- Allergy or hypersensitivity to agents used within the treatment protocol.
- For an indolent lymphoma histology (follicular lymphoma, Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia (SLL/CLL)) or mantle cell lymphoma, the patient should not have an HLA-matched sibling, who would be an eligible donor, available.
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 |
|---|---|---|
| Fludarabine PhosphateFludarabine will be administered by IV over approximately 30 minutes for 4 days. | Drug | Peripheral Blood Stem Cell Transplant |
| MesnaGiven IV over 24 hours starting prior to cyclophosphamide | Drug | Peripheral Blood Stem Cell Transplant |
| CyclophosphamideGiven IV for 2 days | Drug | Peripheral Blood Stem Cell Transplant |
| Total nodal irradiationUndergo total lymphoid irradiation | Radiation | Peripheral Blood Stem Cell Transplant |
| T Cell-Depleted Hematopoietic Stem Cell TransplantationUndergo TCR alpha-beta/DC19-depleted hematopoietic stem cell transplant | Biological | Peripheral Blood Stem Cell Transplant |
| Allogeneic Hematopoietic Stem Cell TransplantationAlso: HSC, HSCTUndergo TCR alpha-beta/DC19-depleted hematopoietic stem cell transplant | Procedure or surgery | Peripheral Blood Stem Cell Transplant |
| Peripheral Blood Stem Cell TransplantationUndergo TCR alpha-beta/CD19-depleted hematopoietic stem cell transplant | Procedure or surgery | Peripheral Blood Stem Cell Transplant |
| Mycophenolate MofetilAlso: MMFGiven PO | Drug | Peripheral Blood Stem Cell Transplant |
| TacrolimusGiven PO or IV ONLY if graft cell content is over 1 x 10^5 cells/kg ideal BW of the patient | Drug | Peripheral Blood Stem Cell Transplant |
| RituximabGiven IV ONLY if graft B cell content exceeds 1 x 10^5 cells/kg ideal BW of the patient | Biological | Peripheral Blood Stem Cell Transplant |
Primary outcome
Number of Participants With Absolute Neutrophil Count >= 500/Mcl for 3 Consecutive Measurements on Different Days and Platelet Count > 20,000/mm^3 With no Platelet Transfusions in the Preceding 7 Days
Time frame: At day 28 after transplantation
To determine engraftment of neutrophils and platelets at 28 days following alpha/beta T-cell depletion using Human Leukocyte Antigen (HLA) haploidentical donors for stem cell transplant in relapsed lymphoma.
6 secondary outcomes
Number of Participants With Grade III-IV Acute GVHD as Determined by International Bone Marrow Transplant Registry (IBMTR) Severity Index Criteria
Time frame: Day +100
Number of Participants With Severe Chronic GVHD
Time frame: Day +180
Number of Participants With Graft Failure
Time frame: Up to 2 years after graft
Number of Participants With Treatment-related Mortality
Time frame: Up to 2 years after graft
Progression-free Survival
Time frame: Median follow up of 1689 days
Overall Survival (OS)
Time frame: Median follow up of 1689 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- UW Carbone Cancer Center Home PageLink 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.
Vaishalee P Kenkre principal investigator
Principal Investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fludarabine Phosphate, Mesna and Cyclophosphamide in people with Lymphoma, run by University of Wisconsin, Madison 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 16 inclusion and 8 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 5 Jan 2022. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2020). 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?
Number of Participants With Absolute Neutrophil Count >= 500/Mcl for 3 Consecutive Measurements on Different Days and Platelet Count > 20,000/mm^3 With no Platelet Transfusions in the Preceding 7 Days (time frame: At day 28 after transplantation). 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 5 Jan 2022.