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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by University of Chicago
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Chicago
ClinicalTrials.gov Identifier:
NCT01839916
First received: April 22, 2013
Last updated: October 14, 2014
Last verified: October 2014
  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: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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:

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Acute Lymphoblastic Leukemia, Childhood Acute Myelocytic Leukemia Acute Myeloid Leukemia, Adult Acute Myeloid Leukemia, Childhood Acute Non Lymphoblastic Leukemia Anaplastic Large Cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Angioimmunoblastic T-cell Lymphoma B-cell Lymphomas Burkitt Lymphoma Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Chronic Myeloproliferative Disorders Cutaneous T-cell Lymphoma Follicular Lymphoma Hairy Cell Leukemia Hodgkin Lymphoma Hodgkin Lymphoma, Childhood Large Granular Lymphocyte Leukemia Leukemia, B-cell, Chronic Leukemia, Myeloid Leukemia, T-cell, Chronic Lymphoblastic Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoma, Small Cleaved-cell, Diffuse Lymphomatoid Granulomatosis Lymphosarcoma Mantle Cell Lymphoma Mycosis Fungoides Myelodysplastic Syndromes Peripheral T-cell Lymphoma Plasmablastic Lymphoma Sezary Syndrome Small Non-cleaved Cell Lymphoma Waldenstrom Macroglobulinemia
U.S. FDA Resources

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: Time to relapse or death as a result of any cause, assessed at 2 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Estimated by cumulative incidence method.

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

  • Treatment-related mortality [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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
Study Start Date: April 2013
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2015 (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

Ages Eligible for Study:   14 Years to 75 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
Investigators
Principal Investigator: Hongtao Liu University of Chicago Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT01839916     History of Changes
Other Study ID Numbers: 12-1191, NCI-2013-00782
Study First Received: April 22, 2013
Last Updated: October 14, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Blast Crisis
Burkitt Lymphoma
Hodgkin Disease
Immunoblastic Lymphadenopathy
Intraocular Lymphoma
Leukemia
Leukemia, Hairy Cell
Leukemia, Large Granular Lymphocytic
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myeloid, Acute
Leukemia, Myeloid, Chronic-Phase
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral

ClinicalTrials.gov processed this record on October 30, 2014