TCR-α/β and CD19 Depleted Stem Cell Grafts From Haplo Donors for HSCT in Relapsed Lymphoma

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02652468
• Other study ID #: UW14113
• Secondary ID: 2015-0996NCI-201
• Status: Completed
• Phase: N/A
• Start date: March 10, 2016
• Est. completion date: September 17, 2021

Study information

• Verified date: December 2021
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: September 17, 2021
• Est. primary completion date: September 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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

• 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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Lymphoma

Intervention

Drug:
• Fludarabine Phosphate
Fludarabine will be administered by IV over approximately 30 minutes for 4 days.
• Mesna
Given IV over 24 hours starting prior to cyclophosphamide
• Cyclophosphamide
Given IV for 2 days

Radiation:
• Total nodal irradiation
Undergo total lymphoid irradiation

Biological:
• T Cell-Depleted Hematopoietic Stem Cell Transplantation
Undergo TCR alpha-beta/DC19-depleted hematopoietic stem cell transplant

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Undergo TCR alpha-beta/DC19-depleted hematopoietic stem cell transplant
• Peripheral Blood Stem Cell Transplantation
Undergo TCR alpha-beta/CD19-depleted hematopoietic stem cell transplant

Drug:
• Mycophenolate Mofetil
Given PO
• Tacrolimus
Given PO or IV ONLY if graft cell content is over 1 x 10^5 cells/kg ideal BW of the patient

Biological:
• Rituximab
Given IV ONLY if graft B cell content exceeds 1 x 10^5 cells/kg ideal BW of the patient

Locations

Country	Name	City	State
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
University of Wisconsin, Madison

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At day 28 after transplantation
Secondary	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.	Day +100
Secondary	Number of Participants With Severe Chronic GVHD	The number of participants with severe chronic GVHD by Day +180 will be reported.	Day +180
Secondary	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.	Up to 2 years after graft
Secondary	Number of Participants With Treatment-related Mortality	Treatment-related mortality is defined as death from any cause other than disease progression.	Up to 2 years after graft
Secondary	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,	Median follow up of 1689 days
Secondary	Overall Survival (OS)		Median follow up of 1689 days

External Links

•   UW Carbone Cancer Center Home Page