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Donor T Cells After Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

This study is currently recruiting participants.
Verified July 2017 by University of Chicago
Sponsor:
ClinicalTrials.gov Identifier:
NCT01839916
First Posted: April 25, 2013
Last Update Posted: July 26, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Chicago
  Purpose
This pilot phase II trial studies how well giving donor T cells after donor stem cell transplant works in treating patients with hematologic malignancies. In a donor stem cell transplant, the donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect.

Condition Intervention Phase
Accelerated Phase Chronic Myelogenous Leukemia Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Blastic Phase Chronic Myelogenous Leukemia Childhood Burkitt Lymphoma Childhood Chronic Myelogenous Leukemia Childhood Diffuse Large Cell Lymphoma Childhood Immunoblastic Large Cell Lymphoma Childhood Myelodysplastic Syndromes Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Phase Chronic Myelogenous Leukemia Cutaneous B-cell Non-Hodgkin Lymphoma de Novo Myelodysplastic Syndromes Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hepatosplenic T-cell Lymphoma Intraocular Lymphoma Nodal Marginal Zone B-cell Lymphoma Noncutaneous Extranodal Lymphoma Peripheral T-cell Lymphoma Post-transplant Lymphoproliferative Disorder Previously Treated Myelodysplastic Syndromes Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Childhood Grade III Lymphomatoid Granulomatosis Recurrent Childhood Large Cell Lymphoma Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Small Noncleaved Cell Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Recurrent/Refractory Childhood Hodgkin Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Hairy Cell Leukemia Relapsing Chronic Myelogenous Leukemia Secondary Myelodysplastic Syndromes Small Intestine Lymphoma Splenic Marginal Zone Lymphoma T-cell Large Granular Lymphocyte Leukemia Testicular Lymphoma Waldenström Macroglobulinemia Biological: therapeutic allogeneic lymphocytes Other: laboratory biomarker analysis Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Prophylactic Dose-Escalation Donor Lymphocyte Infusion After T Cell Depleted Allogeneic Stem Cell Transplant in High Risk Patients With Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • Proportion of patients who are able to receive at least one DLI treatment [ Time Frame: Up to 2 years ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: Time to relapse or death as a result of any cause, assessed at 2 years ]
    Computed using the Kaplan-Meier product-limit estimate and expressed as probabilities with a 95% confidence interval (CI).

  • Overall survival [ Time Frame: At 2 years ]
    Computed using the Kaplan-Meier product-limit estimate and expressed as probabilities with a 95% CI.

  • Rate of acute GVHD (aGVHD) [ Time Frame: Up to 2 years ]
    Estimated by cumulative incidence method.

  • Rate of chronic GVHD (cGVHD) [ Time Frame: Up to 2 years ]
    Estimated by cumulative incidence method.

  • Treatment-related mortality [ Time Frame: Up to 2 years ]
    Estimated by cumulative incidence method. Cumulative incidence of treatment-related mortality with relapse of the original disease as the competing risk will be calculated.


Estimated Enrollment: 56
Actual Study Start Date: April 4, 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (DLI)
Patients receive DLI IV. Treatment repeats every 4-8 weeks for 5 doses in the absence of disease progression or unacceptable toxicity.
Biological: therapeutic allogeneic lymphocytes
Given IV
Other Name: ALLOLYMPH
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the feasibility of escalating dose regimen (EDR) donor lymphocyte infusion (DLI) as measured by the proportion of patients who receive at least one DLI.

SECONDARY OBJECTIVES:

I. To assess progression free survival (PFS) at 2 years after stem cell transplant (SCT) for high-risk hematologic malignancies receiving T-cell depleted grafts followed by escalating dose regimen (EDR) prophylactic DLI compared to historical controls not receiving DLI.

II. To assess the safety of EDR DLI for high-risk hematologic malignancies as measured by cumulative incidence of severe grade III-IV acute graft-versus-host disease (GVHD).

III. To measure outcomes of grade II-IV acute GVHD, non-relapse mortality, overall survival and chronic GVHD of EDR DLI.

IV. To assess the full donor chimerism rate in the CD3 compartment and immune reconstitution after EDR DLI.

OUTLINE:

Patients receive DLI intravenously (IV). Treatment repeats every 4-8 weeks for 5 doses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 2 years.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   14 Years to 75 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • INCLUSION CRITERIA PRIOR TO TRANSPLANT:
  • The clinical trial will be offered to all high risk (defined 3 below) patients with hematologic malignancies who require stem cell transplants as part of their standard of care using matched related or unrelated donors
  • Patients with high risk myeloid or lymphoid malignancies at stem cell transplant following American Society for Blood and Marrow Transplantation (ASBMT) criteria, including but not limited to conditions listed; these criteria apply BEFORE cyto-reductive therapy given within 28 days of planned conditioning:

    • Refractory acute myelogenous or lymphoid leukemia
    • Relapsed acute myelogenous or lymphoid leukemia
    • Myelodysplastic syndromes with 5% or more blasts
    • Chronic myelogenous leukemia in chronic phase 3 or more, blast phase presently, or second accelerated phase
    • Recurrent or refractory malignant lymphoma or Hodgkin's disease with less than a partial response at transplant
  • High risk chronic lymphocytic leukemia defined as no response or stable disease to the most recent treatment regimen
  • DONORS: Matched related or unrelated donor stem cell transplant (SCT) matched at human leukocyte antigen (HLA) A- B, C, and DRB1 by molecular methods; 7 of 8 matched donor acceptable for related donors
  • T-cell depletion with anti-thymocyte globulin (ATG) (rabbit or horse) or at least 30 mg of alemtuzumab total in the conditioning regimen
  • Immune suppression; planned post-transplant immune suppression should include tacrolimus or cyclosporin monotherapy (i.e., calcineurin inhibitor or CN) for alemtuzumab regimens and a second immune suppressant for ATG treated patients; other agents may be used if CN intolerance or toxicity occurs post-transplant
  • Zubrod performance status (PS) 0-2 or equivalent Karnofsky PS
  • Eligible for allogeneic transplant in the treating physicians' judgment and by institutional standards
  • ELIGIBILITY TO RECEIVE DLI POST-TRANSPLANT:
  • Donor lymphocytes available or able to be collected
  • No evidence of disease by standard morphology; minimal residual disease or molecular evidence of disease will not exclude
  • Absolute neutrophil count >= 500/μl
  • Platelet count >= 20,000/μl without transfusion for 7 days
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 5 x upper limit of normal (ULN)
  • Bilirubin =< 3 x ULN
  • No evidence of grade II or higher acute GVHD or chronic GVHD at initiation of first DLI
  • No systemic corticosteroids or immunosuppressive drugs (topical acceptable); replacement steroids for adrenal insufficiency are not excluded

Exclusion Criteria:

  • EXCLUSION CRITERIA PRIOR TO TRANSPLANT:
  • Pregnant or lactating females
  • Hepatitis B with positive viral load prior to transplant conditioning or hepatitis C virus
  • Human immune deficiency virus
  • Psychiatric illness that may make compliance to the clinical protocol unmanageable or may compromise the ability of the patient to give informed consent
  • Creatinine >= 2.0 mg/dL
  • SGOT and SGPT >= 5 x ULN; liver biopsy preferred for such patients
  • Bilirubin >= 3 x ULN (unless Gilbert's syndrome)
  • Diffusing capacity of the lung for carbon monoxide (DLCO) < 50% corrected for hemoglobin
  • Left ventricular ejection fraction or shortening fraction < 40%
  • Unlikely to be able to procure additional donor lymphocytes
  Contacts and Locations
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): NCT01839916


Locations
United States, Illinois
University of Chicago Comprehensive Cancer Center Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Hongtao Liu    773-834-7424    hongtae.liu@uchicago.edu   
Principal Investigator: Hongtao Liu         
Sponsors and Collaborators
University of Chicago
National Cancer Institute (NCI)
Investigators
Principal Investigator: Hongtao Liu University of Chicago Comprehensive Cancer Center
  More Information

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT01839916     History of Changes
Other Study ID Numbers: 12-1191
NCI-2013-00782 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted: April 22, 2013
First Posted: April 25, 2013
Last Update Posted: July 26, 2017
Last Verified: July 2017

Additional relevant MeSH terms:
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma, Follicular
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Burkitt Lymphoma
Lymphoma, T-Cell
Lymphoma, Large-Cell, Immunoblastic
Plasmablastic Lymphoma
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, T-Cell, Cutaneous
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Waldenstrom Macroglobulinemia
Lymphoma, Large-Cell, Anaplastic