Brief Title
Donor T Cells After Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies
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
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Percentage of Patients Who Are Able to Receive at Least One DLI Treatment
Secondary Outcome
Progression Free Survival (PFS)
Condition
Accelerated Phase Chronic Myelogenous Leukemia
Intervention
therapeutic allogeneic lymphocytes
Study Arms / Comparison Groups
Treatment (DLI)
Description: Patients receive DLI IV. Treatment repeats every 4-8 weeks for 5 doses in the absence of disease progression or unacceptable toxicity.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
77
Start Date
April 4, 2013
Completion Date
August 2018
Primary Completion Date
August 2018
Eligibility 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
Gender
All
Ages
14 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Hongtao Liu, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01839916
Organization ID
12-1191
Secondary IDs
NCI-2013-00782
Responsible Party
Sponsor
Study Sponsor
University of Chicago
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Hongtao Liu, Principal Investigator, University of Chicago Comprehensive Cancer Center
Verification Date
June 2019