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

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ClinicalTrials.gov Identifier: NCT02652468
Recruitment Status : Recruiting
First Posted : January 11, 2016
Last Update Posted : March 8, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Wisconsin, Madison

Brief Summary:

To determine engraftment of neutrophils and platelets at 28 days following alpha/beta T-cell and CD19 cell depletion using HLA haploidentical donors for peripheral blood stem cell transplant in relapsed lymphoma.

Assess incidence of acute GVHD (Graft versus Host Disease), 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.


Condition or disease Intervention/treatment Phase
Lymphoma 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 Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 in Patients With Relapsed Lymphoma
Actual Study Start Date : March 10, 2016
Estimated Primary Completion Date : March 15, 2019
Estimated Study Completion Date : March 15, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Peripheral Blood Stem Cell Transplant

PREPARATIVE REGIMEN: Patients 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. Patients also undergo total nodal irradiation on day -1.

TRANSPLANT: Patients undergo 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 patient BW, patients may receive a second graft on day 1.

GVHD PROPHYLAXIS: Patients receive mycophenolate mofetil 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 patient).

Drug: Fludarabine Phosphate
Fludarabine will be administered by IV over approximately 30 minutes for 4 days.
Drug: Mesna
Given IV over 24 hours starting prior to cyclophosphamide
Drug: 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
Other Names:
  • HSC
  • HSCT
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo TCR alpha-beta/CD19-depleted hematopoietic stem cell transplant
Drug: Mycophenolate Mofetil
Given PO
Other Name: MMF
Drug: 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



Primary Outcome Measures :
  1. Rate of engraftment, as defined as 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 HLA haploidentical donors for stem cell transplant in relapsed lymphoma. Will be obtained from the Kaplan-Meier (KM) estimates along with 95% confidence intervals.


Secondary Outcome Measures :
  1. Incidence of grade III-IV acute GVHD as determined by IBMTR Severity Index criteria [ Time Frame: Day +100 ]
    The cumulative incidence of grade III - IV acute GVHD by Day +100 will be determined. Will be analyzed using KM method. Acute GVHD will be obtained from t he KM estimates along with 95% confidence intervals.

  2. Incidence of chronic GVHD [ Time Frame: Day +180 ]
    The cumulative incidence of severe chronic GVHD by Day +180 will be recorded. Will be analyzed using KM method. Chronic GVHD will be obtained from the KM estimates along with 95% confidence intervals.

  3. Incidence of graft failure [ Time Frame: Up to 1 year 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. Will be analyzed using KM method.

  4. Treatment-related mortality [ Time Frame: Up to 1 year after graft ]
    Time to treatment-related mortality - defined as death from any cause other than disease progression - will be analyzed using KM method

  5. Progression-free survival [ Time Frame: Time before any progression by either PET/CT or bone marrow, assessed up to 1 year ]
    Progression-free survival will be analyzed using KM method.

  6. Overall survival (OS) [ Time Frame: Up to 1 year ]
    OS will be obtained from the KM estimates along with 95% confidence intervals.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must meet one of the following disease criteria within 24 months of registration. Salvage therapy is allowed between the patient meeting one of the below criterion and registration. Patients 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: DLCO (corrected for hemoglobin) > 40%; and FEV1 > 50%
  • Cardiac: 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 GFR by 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 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 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, 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02652468


Contacts
Contact: Cancer Connect 800-622-8922 cancerconnect@uwcarbone.wisc.edu

Locations
United States, Wisconsin
University of Wisconsin Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53705
Contact: Cancer Center    800-622-8922    cancerconnect@uwcarbone.wisc.edu   
Contact: Vaishalee Kenkre    608-263-1699    vpkenkre@medicine.wisc.edu   
Sponsors and Collaborators
University of Wisconsin, Madison
National Cancer Institute (NCI)
Investigators
Principal Investigator: Vaishalee P Kenkre Principal Investigator

Additional Information:
Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT02652468     History of Changes
Other Study ID Numbers: UW14113
2014-0996 ( Other Identifier: IRB )
P30CA014520 ( U.S. NIH Grant/Contract )
NCI-2015-02269 ( Registry Identifier: CTRP )
First Posted: January 11, 2016    Key Record Dates
Last Update Posted: March 8, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Tacrolimus
Fludarabine phosphate
Rituximab
Fludarabine
Mycophenolic Acid
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Calcineurin Inhibitors
Enzyme Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents