Post-transplant Cyclophosphamide and Sirolimus Following Reduced Intensity Conditioning (RIC) Transplant

NCT01244906 | Completed Phase 2 Results

• 1 other identifier: NSH 911
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This trial will evaluate the safety and efficacy of post-transplant Cy and sirolimus following reduced intensity allogeneic SCT. It is hoped that the combination of a reduced intensity preparative regimen with a calcineurin-free GVHD prophylaxis regimen will decrease the risk of acute and chronic GVHD, by both limiting mucosal toxicity and augmenting immune reconstitution, thereby improving the safety of the procedure. The past experience with post-transplant Cy suggests that SCT recipients will attain rapid donor T cell chimerism, which the investigators hope will translate into improved disease control through the well documented graft-versus-malignancy effects of donor T cells.

Conditions

Hematologic Neoplasms

Keywords

Chronic Myelogenous Leukemia; Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Myelofibrosis; Acute Lymphocytic Leukemia; Acute Lymphoblastic Lymphoma; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Low-grade non-Hodgkin's Lymphoma; Mantle Cell Lymphoma; Hodgkin Lymphoma; Myeloma

Outcome Measures

Primary Outcomes (1)

• Incidence of GVHD

  To estimate the incidence of graft-versus-host disease (GVHD) when utilizing post-transplant cyclophosphamide (Cy) and sirolimus for GVHD prophylaxis following reduced intensity allogeneic hematopoietic stem cell transplantation (SCT) in patients with high risk hematologic malignancies.

  1 year

Secondary Outcomes (5)

• Incidence of Absolute Neutrophil Count (ANC)/Platelet Engraftment

  Approximately Day 30

• Number of Participants With Non-Relapse Mortality

  1 year

• Number of Patients With Disease Free Survival at 2 Years

  2 years

• Number of Patients to Achieve Full Donor Chimerism

  1 year

• Number of Patients With Overall Survival at 2 Years.

  2 years

Study Arms (1)

Reduced Intensity Allogeneic Stem Cell Transplantation

EXPERIMENTAL

All patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Patients will receive fludarabine, busulfan and cyclophosphamide as the conditioning regimen prior to an allo SCT. Patients will then receive 2 doses of cyclophosphamide post-transplant and utilize sirolimus and mycophenolate mofetil (in mismatched transplants) as GVHD prophylaxis.

Reduced Intensity Allogeneic Stem Cell Transplantation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Availability of a 7/8 or 8/8 (HLA-A, B, C, DR) related or unrelated donor
• Age 18-75
• One of the following high-risk malignancies
• Chronic Myelogenous Leukemia
• Acute Myelogenous Leukemia
• Myelodysplastic Syndrome
• Myelofibrosis
• Acute Lymphocytic Leukemia
• Acute Lymphoblastic Lymphoma
• Chronic Lymphocytic Leukemia
• Prolymphocytic Leukemia
• Low-grade non-Hodgkin's Lymphoma
• Mantle Cell Lymphoma
• Hodgkin Lymphoma
• Myeloma

You may not qualify if:

• Poor cardiac function (EF \<40%)
• Poor pulmonary function (FEV1 and FVC \<50% predicted)
• Poor liver function (bilirubin \>/= 2 mg/dl not due to hemolysis, Gilbert's or primary malignancy)
• Poor renal function (creatinine \>/= 2 mg/dl or creatinine clearance \<40mL/min)
• Karnofsky status \<70%
• HIV positive

Sponsors & Collaborators

• Northside Hospital, Inc.: lead
• Blood and Marrow Transplant Group of Georgia: collaborator

Study Sites (1)

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Related Publications (21)

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• Basara N, Schulze A, Wedding U, Mohren M, Gerhardt A, Junghanss C, Peter N, Dolken G, Becker C, Heyn S, Kliem C, Lange T, Krahl R, Ponisch W, Fricke HJ, Sayer HG, Al-Ali H, Kamprad F, Niederwieser D; East German Study Group Hematology and Oncology (OSHO). Early related or unrelated haematopoietic cell transplantation results in higher overall survival and leukaemia-free survival compared with conventional chemotherapy in high-risk acute myeloid leukaemia patients in first complete remission. Leukemia. 2009 Apr;23(4):635-40. doi: 10.1038/leu.2008.352. Epub 2009 Jan 8.

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  PMID: 11986199 BACKGROUND

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• Trenado A, Charlotte F, Fisson S, Yagello M, Klatzmann D, Salomon BL, Cohen JL. Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia. J Clin Invest. 2003 Dec;112(11):1688-96. doi: 10.1172/JCI17702.

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• Zorn E, Kim HT, Lee SJ, Floyd BH, Litsa D, Arumugarajah S, Bellucci R, Alyea EP, Antin JH, Soiffer RJ, Ritz J. Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease. Blood. 2005 Oct 15;106(8):2903-11. doi: 10.1182/blood-2005-03-1257. Epub 2005 Jun 21.

  PMID: 15972448 BACKGROUND

• Rieger K, Loddenkemper C, Maul J, Fietz T, Wolff D, Terpe H, Steiner B, Berg E, Miehlke S, Bornhauser M, Schneider T, Zeitz M, Stein H, Thiel E, Duchmann R, Uharek L. Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD. Blood. 2006 Feb 15;107(4):1717-23. doi: 10.1182/blood-2005-06-2529. Epub 2005 Nov 8.

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• Mayumi H, Himeno K, Tanaka K, Tokuda N, Fan JL, Nomoto K. Drug-induced tolerance to allografts in mice. XII. The relationships between tolerance, chimerism, and graft-versus-host disease. Transplantation. 1987 Aug;44(2):286-90. doi: 10.1097/00007890-198708000-00021.

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• Luznik L, Engstrom LW, Iannone R, Fuchs EJ. Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation. Biol Blood Marrow Transplant. 2002;8(3):131-8. doi: 10.1053/bbmt.2002.v8.pm11939602.

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• Luznik L, Bolanos-Meade J, Zahurak M, Chen AR, Smith BD, Brodsky R, Huff CA, Borrello I, Matsui W, Powell JD, Kasamon Y, Goodman SN, Hess A, Levitsky HI, Ambinder RF, Jones RJ, Fuchs EJ. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010 Apr 22;115(16):3224-30. doi: 10.1182/blood-2009-11-251595. Epub 2010 Feb 2.

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• Uberti JP, Ayash L, Braun T, Reynolds C, Silver S, Ratanatharathorn V. Tacrolimus as monotherapy or combined with minidose methotrexate for graft-versus-host disease prophylaxis after allogeneic peripheral blood stem cell transplantation: long-term outcomes. Bone Marrow Transplant. 2004 Sep;34(5):425-31. doi: 10.1038/sj.bmt.1704594.

  PMID: 15273705 BACKGROUND

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Primary Myelofibrosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Lymphoma, Mantle-Cell; Hodgkin Disease; Neoplasms, Plasma Cell

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Scott R. Solomon, MD
• Organization: Blood and Marrow Transplant Group of Georgia

ssolomon@bmtga.com

404-255-1930

Study Officials

• Scott R Solomon, MD

  Blood and Marrow Transplant Group of Georgia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: November 18, 2010
• First Posted: November 19, 2010
• Study Start: December 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 1, 2015
• Results First Posted: March 17, 2015

Record last verified: 2015-01

Locations

US (1)