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

NCT02458235 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 140813NCI-2015-02240
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Acute Myelogenous Leukemia; Acute Lymphoid Leukemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndrome

Keywords

pediatric leukemia myelodysplastic syndrome azacitidine

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (2)

• Median Relapse-free Survival

  Up to 2 years

• Median Time to Relapse

  Up to 2 years

Study Arms (1)

Azacitidine/donor lymphocyte infusion

EXPERIMENTAL

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 Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI.

Drug: azacitidine; Biological: donor lymphocyte infusion

Interventions

azacitidine DRUG

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

Also known as: Vidaza®, Ladakamycin

Azacitidine/donor lymphocyte infusion

donor lymphocyte infusion BIOLOGICAL

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.

Azacitidine/donor lymphocyte infusion

Eligibility Criteria

• Age: Up to 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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%

Sponsors & Collaborators

• University of California, San Francisco: lead
• Hellman Foundation: collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Related 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 with Acute Leukemia. Blood 2016; 128 (22): 4805. https://doi.org/10.1182/blood.V128.22.4805.4805

  RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Dr. Christopher Dvorak, MD
• Organization: University of California, San Francisco

Christopher.Dvorak@ucsf.edu

(415) 476-0554

Study Officials

• Christopher C Dvorak, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2015
• First Posted: June 1, 2015
• Study Start: June 2, 2015
• Primary Completion: March 15, 2019
• Study Completion: March 15, 2019
• Last Updated: October 12, 2020
• Results First Posted: October 12, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)