Clinical trial NCT01839916: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-04-25
Enrollment: 77
Sex: ALL
Minimum age (years): 14
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Patients Who Are Able to Receive at Least One DLI Treatment
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: At 2 years
measure: Rate of Acute GVHD (aGVHD) With Any Grade
timeFrame: At 1 year and 2 year
measure: Rate of Chronic GVHD (cGVHD)
timeFrame: At 1 year and 2 year
measure: Treatment-related Mortality
timeFrame: At 2 year
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
Study officials:
affiliation: University of Chicago Comprehensive Cancer Center
name: Hongtao Liu
role: PRINCIPAL_INVESTIGATOR
References: