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

NCT02652468 | Completed Results DMC FDA Device

• 6 other identifiers: UW141132015-0996NCI-2015-02269A534260SMPH\MEDICINE\HEM-ONCProtocol Version 4/24/2020
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Lymphoma

Outcome Measures

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

  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 Outcomes (6)

• Number of Participants With Grade III-IV Acute GVHD as Determined by International Bone Marrow Transplant Registry (IBMTR) Severity Index Criteria

  Day +100

• Number of Participants With Severe Chronic GVHD

  Day +180

• Number of Participants With Graft Failure

  Up to 2 years after graft

• Number of Participants With Treatment-related Mortality

  Up to 2 years after graft

• Progression-free Survival

  Median follow up of 1689 days

Study Arms (1)

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).

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

Interventions

Fludarabine Phosphate DRUG

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

Peripheral Blood Stem Cell Transplant

Mesna DRUG

Given IV over 24 hours starting prior to cyclophosphamide

Peripheral Blood Stem Cell Transplant

Cyclophosphamide DRUG

Given IV for 2 days

Peripheral Blood Stem Cell Transplant

Total nodal irradiation RADIATION

Undergo total lymphoid irradiation

Peripheral Blood Stem Cell Transplant

T Cell-Depleted Hematopoietic Stem Cell Transplantation BIOLOGICAL

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

Peripheral Blood Stem Cell Transplant

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

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

Also known as: HSC, HSCT

Peripheral Blood Stem Cell Transplant

Peripheral Blood Stem Cell Transplantation PROCEDURE

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

Peripheral Blood Stem Cell Transplant

Mycophenolate Mofetil DRUG

Given PO

Also known as: MMF

Peripheral Blood Stem Cell Transplant

Tacrolimus DRUG

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

Peripheral Blood Stem Cell Transplant

Rituximab BIOLOGICAL

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

Peripheral Blood Stem Cell Transplant

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53705, United States

Location

Related Links

• UW Carbone Cancer Center Home Page

MeSH Terms

Conditions

Lymphoma

Interventions

fludarabine phosphate; Mesna; Cyclophosphamide; Peripheral Blood Stem Cell Transplantation; Mycophenolic Acid; Tacrolimus; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Vaishalee Kenkre
• Organization: University of Madison Carbone Cancer Center

vpkenkre@medicine.wisc.edu

(608) 263-1699

Study Officials

• Vaishalee P Kenkre

  Principal Investigator

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2016
• First Posted: January 11, 2016
• Study Start: March 10, 2016
• Primary Completion: September 1, 2018
• Study Completion: September 17, 2021
• Last Updated: January 5, 2022
• Results First Posted: January 13, 2020

Record last verified: 2021-12

Locations

US (1)