Donor Lymphocyte Infusion With Azacitidine to Prevent Hematologic Malignancy Relapse After Stem Cell Transplantation

Myelodysplastic Syndrome Clinical Trial

Official title:

A Phase II Study of Risk-adapted Donor Lymphocyte Infusion and Azacitidine for the Prevention of Hematologic Malignancy Relapse Following Allogeneic Stem Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02458235
• Other study ID #: 140813
• Secondary ID: NCI-2015-02240
• Status: Completed
• Phase: Phase 2
• Start date: June 2, 2015
• Est. completion date: March 15, 2019

Study information

• Verified date: October 2020
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to determine whether post-transplant consolidation with azacitidine combined with donor lymphocyte infusion (DLI) is a safe and effective approach for the prevention of relapse in pediatric and young adult patients with hematologic malignancies who have undergone hematopoietic stem cell transplantation (HSCT).

Description:

This is a phase II single-arm trial of azacitidine (IV or SC) in combination with escalating donor lymphocyte infusion (DLI). Patients will be enrolled on the study by day +28 +/- 7 post-transplant, prior to withdrawal of immunosuppression or administration of donor lymphocyte infusion (DLI). They will have donor chimerism and minimal residual disease (MRD) testing from peripheral blood (PB) and bone marrow (BM) on day +28 ± 7. Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative MRD results. Depending on risk assessment, immunosuppression will be tapered according to standard or fast schedules, and patients (with the exception of low-risk ALL patients) will receive one cycle of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days). After tapering immunosuppression, chimerism will be repeated and patients will receive up to 6 additional cycles of low-dose azacitidine, depending on risk assessment. For patients who meet criteria for high risk of relapse, azacitidine will be combined with escalating doses of DLI for a maximum of 7 cycles in total. Risk and safety assessments, including routine laboratory parameters, donor chimerism, minimal residual disease, and GHVD activity will be assessed following each cycle. Chimerism and minimal residual disease testing will be repeated every cycle by peripheral blood (PB), and bone marrow (BM) will be tested every other cycle. Patients will be followed by laboratory monitoring and physician evaluation prior to each cycle, and will be followed for two years post-transplant to study toxicity and GVHD outcomes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: March 15, 2019
• Est. primary completion date: March 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 29 Years

Eligibility

Inclusion Criteria:

• Patients age 0 - 29.9 years undergoing allogeneic peripheral blood stem cell transplant

• Patients with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL)

• Patients with juvenile myelomonocytic leukemia (JMML)

• Patients with myelodysplastic syndrome (MDS)

Exclusion Criteria:

• Patients who have had a prior transplant.

• Patients with Fanconi anemia or other cancer-predisposition syndromes

• Patients with expected survival <12 weeks

• Lansky score <60%

Related Conditions & MeSH terms

• Acute Lymphoid Leukemia
• Acute Myelogenous Leukemia
• Hematologic Neoplasms
• Juvenile Myelomonocytic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Drug:
• azacitidine
40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals

Biological:
• donor lymphocyte infusion
For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.

Locations

Country	Name	City	State
United States	University of California San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Hellman Foundation

Country where clinical trial is conducted

United States, 

References & Publications (1)

Justin T. Wahlstrom, Biljana N. Horn, Carol Fraser-Browne, Rebecca Hoeweler, Ying Lu, Alexis Melton, Jennifer Willert, Christopher C. Dvorak; Azacitidine Administration Following Hematopoietic Stem Cell Transplantation Is Safe and Feasible in Children wit

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relapse Rate	Relapse rate will be estimated using a percentage of participants who relapsed. It is assumed that the rate of relapse in pediatric acute leukemia post-transplant would be 40%, azacitidine +/- Donor Lymphocyte Infusion (DLI) would reduce the 2-year relapse rate by approximately 40% to a rate of 25%.	Up to 2 years
Primary	Frequency of System Specific Grade 3 or Higher Treatment-related Adverse Events	Frequency of system specific adverse events of interest include renal, hepatic, cardiac, pulmonary, or neurologic toxicities. Toxicities will be graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	Up to 2 years
Primary	Proportion of Participants With Acute and Chronic Graft Versus Host Disease (GVHD)	Proportion of participants with Grade 3-4 acute GVHD and moderate to severe chronic GVHD will be reported.	Up to 2 years
Primary	Proportion of Participants With Serious Infection	The proportion of participants will be reported for Grade 3-4 invasive fungal infection or disease caused by viral infections	Up to 2 years
Primary	Proportion of Participants With Severe Hematologic Toxicity Including Graft Failure	The proportion of participants will be reported for Grade 4 severe hematologic toxicities including graft failure	Up to 2 years
Primary	Number of Participants Whom Had >2 Dose Reductions for Any Reason	The number of participants whom had greater than 2 dose reductions for any reason.	Up to 2 years
Secondary	Median Relapse-free Survival	Release-free survival rate is defined as the median length of time after beginning treatment that the participant survives without progression or relapse, reported in months	Up to 2 years
Secondary	Median Time to Relapse	Time to relapse is defined as the length of time after beginning treatment until the participant has experienced a relapse in disease, measured in months.	Up to 2 years