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

Recurrent Mantle Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01839916
• Other study ID #: 12-1191
• Secondary ID: NCI-2013-00782
• Status: Completed
• Phase: Phase 2
• Start date: April 4, 2013
• Est. completion date: August 2018

Study information

• Verified date: June 2019
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: August 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• 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
• Blast Crisis
• Blastic Phase Chronic Myelogenous Leukemia
• Burkitt Lymphoma
• 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
• Hodgkin Disease
• Intraocular Lymphoma
• Leukemia
• Leukemia, Hairy Cell
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• 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
• Lymphomatoid Granulomatosis
• Lymphoproliferative Disorders
• Mycoses
• Mycosis Fungoides
• Myelodysplastic Syndromes
• Nodal Marginal Zone B-cell Lymphoma
• Noncutaneous Extranodal Lymphoma
• Peripheral T-cell Lymphoma
• Plasmablastic Lymphoma
• Post-transplant Lymphoproliferative Disorder
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• 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
• Sezary Syndrome
• Small Intestine Lymphoma
• Splenic Marginal Zone Lymphoma
• Syndrome
• T-cell Large Granular Lymphocyte Leukemia
• Testicular Lymphoma
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Biological:
• therapeutic allogeneic lymphocytes
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
University of Chicago	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Patients Who Are Able to Receive at Least One DLI Treatment		Up to 2 years
Secondary	Progression Free Survival (PFS)	Time to relapse or death as a result of any cause was evaluated at 2 years and the progression free survival rate was reported.	2 years
Secondary	Overall Survival (OS)	Computed using the Kaplan-Meier product-limit estimate and expressed as probabilities with a 95% CI.	At 2 years
Secondary	Rate of Acute GVHD (aGVHD) With Any Grade	Estimated by cumulative incidence method.	At 1 year and 2 year
Secondary	Rate of Chronic GVHD (cGVHD)	Estimated by cumulative incidence method.	At 1 year and 2 year
Secondary	Treatment-related Mortality	Estimated by cumulative incidence method. Cumulative incidence of treatment-related mortality with relapse of the original disease as the competing risk will be calculated.	At 2 year