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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01839916
Recruitment Status : Completed
First Posted : April 25, 2013
Results First Posted : August 7, 2019
Last Update Posted : August 7, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Chicago

Tracking Information
First Submitted Date  ICMJE April 22, 2013
First Posted Date  ICMJE April 25, 2013
Results First Submitted Date  ICMJE June 12, 2019
Results First Posted Date  ICMJE August 7, 2019
Last Update Posted Date August 7, 2019
Actual Study Start Date  ICMJE April 4, 2013
Actual Primary Completion Date August 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2019)
Percentage of Patients Who Are Able to Receive at Least One DLI Treatment [ Time Frame: Up to 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 22, 2013)
Proportion of patients who are able to receive at least one DLI treatment [ Time Frame: Up to 2 years ]
Change History Complete list of historical versions of study NCT01839916 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2019)
  • Progression Free Survival (PFS) [ Time Frame: 2 years ]
    Time to relapse or death as a result of any cause was evaluated at 2 years and the progression free survival rate was reported.
  • Overall Survival (OS) [ 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) With Any Grade [ Time Frame: At 1 year and 2 year ]
    Estimated by cumulative incidence method.
  • Rate of Chronic GVHD (cGVHD) [ Time Frame: At 1 year and 2 year ]
    Estimated by cumulative incidence method.
  • Treatment-related Mortality [ Time Frame: At 2 year ]
    Estimated by cumulative incidence method. Cumulative incidence of treatment-related mortality with relapse of the original disease as the competing risk will be calculated.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2013)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Donor T Cells After Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies
Official Title  ICMJE Pilot Study of Prophylactic Dose-Escalation Donor Lymphocyte Infusion After T Cell Depleted Allogeneic Stem Cell Transplant in High Risk Patients With Hematologic Malignancies
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Biological: therapeutic allogeneic lymphocytes
    Given IV
    Other Name: ALLOLYMPH
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE 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.
Interventions:
  • Biological: therapeutic allogeneic lymphocytes
  • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 17, 2019)
77
Original Estimated Enrollment  ICMJE
 (submitted: April 22, 2013)
56
Actual Study Completion Date  ICMJE August 2018
Actual Primary Completion Date August 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 14 Years to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01839916
Other Study ID Numbers  ICMJE 12-1191
NCI-2013-00782 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Chicago
Study Sponsor  ICMJE University of Chicago
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Hongtao Liu University of Chicago Comprehensive Cancer Center
PRS Account University of Chicago
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP