A Study of Withdrawal of Immunosuppression and Donor Lymphocyte Infusions Following Allogeneic Transplant for Pediatric Hematologic Malignancies

NCT01036009 | Completed Phase 2 Results DMC

• 1 other identifier: CC# 09082
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 2

Brief Summary

There is no curative therapy once acute leukemia patients relapse after transplant. Patients who develop clinically significant graft versus host disease (GVHD) have a lower rate of relapse than those who do not develop GVHD. We are initiating this study of post-transplant fast withdrawal of immunosuppression and donor lymphocyte infusions, with a goal of achieving full donor chimerism in children with hematologic malignancies. If our hypothesis that full donor chimerism results in leukemia-free survival is correct, using immune modulation to achieve full donor chimerism should decrease relapse rate and thus increase survival. The goal of this Phase II study is to identify if achieving full donor chimerism in whole blood CD3+ and leukemia-specific (CD14/15+, CD19+, CD33+ and CD34+) subset may decrease the risk of relapse of patients undergoing allogeneic transplant for hematologic malignancy.

Conditions

Acute Leukemia; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Biphenotypic Leukemia; Pre-leukemic Syndromes; Monosomy 7; Bone Marrow Clonal Malformations; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndromes; Chronic Myelogenous Leukemia

Keywords

Hematologic; Malignancy; Leukemia; Pre-leukemic; Allogeneic; Transplant; Pediatric

Outcome Measures

Primary Outcomes (1)

• Relapse at 2 Years Post-transplant.

  Definition of relapse was \>5 % blasts in bone marrow

  2 years post transplant.

Secondary Outcomes (3)

• 2 Years Post-transplant Survival.

  2 years post transplant

• The Incidence of Acute Graft Versus Host Disease (aGVHD).

  2 years post transplant

• The Incidence of Chronic GVHD (cGVHD).

  2 years post transplant

Study Arms (2)

Group I: Observation

NO INTERVENTION

Group I (observation): Patients with full donor chimerism and no evidence of MRD continue to undergo clinical monitoring for acute and chronic graft-vs-host disease and relapse until 3 years post-transplant. Patients undergo repeat chimerism testing at 12 and 24 months post-transplant.

Group II: Intervention

EXPERIMENTAL

Group II (intervention): Patients undergo withdrawal of immunosuppression and receive donor lymphocyte infusions between days 60-365 post-transplant (or until full donor chimerism is achieved). Patients also undergo clinical monitoring and repeat chimerism testing as in group I.

Other: Withdrawal of immunosuppression and donor lymphocyte infusion

Interventions

Withdrawal of immunosuppression and donor lymphocyte infusion OTHER

Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.

Group II: Intervention

Eligibility Criteria

• Age: 6 Months - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 6 months - 25 years.
• Diagnoses of acute leukemia (AML, ALL, biphenotypic leukemia), pre-leukemic syndromes (monosomy 7 or other bone marrow clonal malformations), JMML, myelodysplastic syndromes or CML.
• Undergoing an allogeneic transplant as standard care.
• Performance status: Karnofsky/Lansky\>60%.
• Availability of pre-transplant recipient's DNA and donor's DNA for chimerism testing. This could be DNA or material from which DNA could be extracted. Frozen blood would be preferred. For some patients, post transplant specimens that are not infiltrated with donor cells may be used.
• Bone marrow or PBMTC as stem cell source.HLA matching: donor and recipient should be matched at a minimum of 7/8 antigens (A,B,C and DrB1) for bone marrow and PBMTC transplants.
• No history of ≥grade III acute GVHD.

You may not qualify if:

• Treatment on other experimental protocols, if withdrawal of immunosuppression interferes with procedures of follow-up on the primary study.
• Leukemia relapse defined as \> 5% blasts on bone marrow exam or \>1% leukemia cells by immunoflow MRD, or presence of extramedullary leukemia.
• History of acute GVHD ≥ stage III or with any degree of active acute or cGVHD.
• On steroids for any reason.
• Any condition that compromises compliance with the objectives and procedures of this protocol, as judged by the principal investigator.
• Cells for DLI cannot be obtained from the donor.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Johns Hopkins All Children's Hospital: collaborator

Study Sites (2)

University of California

San Francisco, California, 94115, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Related Publications (2)

• Horn B, Soni S, Khan S, Petrovic A, Breslin N, Cowan M, Pelle-Day G, Cooperstein E, Baxter-Lowe LA. Feasibility study of preemptive withdrawal of immunosuppression based on chimerism testing in children undergoing myeloablative allogeneic transplantation for hematologic malignancies. Bone Marrow Transplant. 2009 Mar;43(6):469-76. doi: 10.1038/bmt.2008.339. Epub 2008 Oct 27.

  PMID: 18955982 BACKGROUND

• Horn B, Petrovic A, Wahlstrom J, Dvorak CC, Kong D, Hwang J, Expose-Spencer J, Gates M, Cowan MJ. Chimerism-based pre-emptive immunotherapy with fast withdrawal of immunosuppression and donor lymphocyte infusions after allogeneic stem cell transplantation for pediatric hematologic malignancies. Biol Blood Marrow Transplant. 2015 Apr;21(4):729-37. doi: 10.1016/j.bbmt.2014.12.029. Epub 2015 Jan 31.

  PMID: 25644958 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Chromosome 7, monosomy; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neoplasms; Leukemia

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Biljana Horn
• Organization: Benioff Children's Hospital at UCSF

hornb@peds.ucsf.edu

415 476 2188

Study Officials

• Biljana Horn, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2009
• First Posted: December 21, 2009
• Study Start: October 1, 2009
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2015
• Last Updated: June 23, 2016
• Results First Posted: October 31, 2014

Record last verified: 2016-05

Locations

US (2)