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Completed

NCT Number: NCT02652468

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

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Key information

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53705, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

fludarabine phosphate

Drug

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

Mesna

Drug

Given IV over 24 hours starting prior to cyclophosphamide

Cyclophosphamide

Drug

Given IV for 2 days

Total Nodal Irradiation

Radiation

Undergo total lymphoid irradiation

T Cell-Depleted Hematopoietic Stem Cell Transplantation

Biological

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

allogeneic hematopoietic stem cell transplantation

Procedure

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

Other names: HSC, HSCT

peripheral blood stem cell transplantation

Procedure

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

Mycophenolate mofetil

Drug

Given PO

Other names: MMF

Tacrolimus

Drug

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

Rituximab

Biological

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

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

    The number of participants with grade III - IV acute Graft versus host disease (GVHD) by Day +100 is reported.

  2. Number of Participants With Severe Chronic GVHD

    Time frame: Day +180

    The number of participants with severe chronic GVHD by Day +180 will be reported.

  3. Number of Participants With Graft Failure

    Time frame: Up to 2 years after graft

    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.

  4. Number of Participants With Treatment-related Mortality

    Time frame: Up to 2 years after graft

    Treatment-related mortality is defined as death from any cause other than disease progression.

  5. Progression-free Survival

    Time frame: Median follow up of 1689 days

    Progression-free survival will be analyzed as time before any progression by either Positron Emission Tomography/Computed Tomography (PET/CT) or bone marrow,

  6. Overall Survival (OS)

    Time frame: Median follow up of 1689 days

Sponsors and collaborators

Lead sponsor

University of Wisconsin, Madison

Other

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2018
Study completion
2021
First posted
Jan 11, 2016
Registry last updated
Jan 5, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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