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

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-10

Study Completion Date

2021-09-17

Brief Summary

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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.

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Detailed Description

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Conditions

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Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Peripheral Blood Stem Cell Transplant

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).

Group Type EXPERIMENTAL

Fludarabine Phosphate

Intervention Type DRUG

Fludarabine will be administered by IV over approximately 30 minutes for 4 days.

Mesna

Intervention Type DRUG

Given IV over 24 hours starting prior to cyclophosphamide

Cyclophosphamide

Intervention Type DRUG

Given IV for 2 days

Total nodal irradiation

Intervention Type RADIATION

Undergo total lymphoid irradiation

T Cell-Depleted Hematopoietic Stem Cell Transplantation

Intervention Type BIOLOGICAL

Undergo TCR alpha-beta/DC19-depleted hematopoietic stem cell transplant

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo TCR alpha-beta/DC19-depleted hematopoietic stem cell transplant

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo TCR alpha-beta/CD19-depleted hematopoietic stem cell transplant

Mycophenolate Mofetil

Intervention Type DRUG

Given PO

Tacrolimus

Intervention Type DRUG

Given PO or IV ONLY if graft cell content is over 1 x 10\^5 cells/kg ideal BW of the patient

Rituximab

Intervention Type BIOLOGICAL

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

Interventions

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Fludarabine Phosphate

Fludarabine will be administered by IV over approximately 30 minutes for 4 days.

Intervention Type DRUG

Mesna

Given IV over 24 hours starting prior to cyclophosphamide

Intervention Type DRUG

Cyclophosphamide

Given IV for 2 days

Intervention Type DRUG

Total nodal irradiation

Undergo total lymphoid irradiation

Intervention Type RADIATION

T Cell-Depleted Hematopoietic Stem Cell Transplantation

Undergo TCR alpha-beta/DC19-depleted hematopoietic stem cell transplant

Intervention Type BIOLOGICAL

Allogeneic Hematopoietic Stem Cell Transplantation

Undergo TCR alpha-beta/DC19-depleted hematopoietic stem cell transplant

Intervention Type PROCEDURE

Peripheral Blood Stem Cell Transplantation

Undergo TCR alpha-beta/CD19-depleted hematopoietic stem cell transplant

Intervention Type PROCEDURE

Mycophenolate Mofetil

Given PO

Intervention Type DRUG

Tacrolimus

Given PO or IV ONLY if graft cell content is over 1 x 10\^5 cells/kg ideal BW of the patient

Intervention Type DRUG

Rituximab

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

Intervention Type BIOLOGICAL

Other Intervention Names

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HSC HSCT MMF

Eligibility Criteria

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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.

Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Vaishalee P Kenkre

Role: PRINCIPAL_INVESTIGATOR

Principal Investigator

Locations

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University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document