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Hematologic NeoplasmsPhase 2NCT01244906

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

A Phase 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation in people with Hematologic Neoplasms, run by Northside Hospital, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Hematologic Neoplasms
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
Dec 2010to Dec 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 15Show fewer
  • Myelofibrosis
  • Acute Lymphocytic Leukemia
  • Acute Lymphoblastic Lymphoma
  • Chronic Lymphocytic Leukemia
  • Prolymphocytic Leukemia
  • Low-grade non-Hodgkin's Lymphoma
  • Mantle Cell Lymphoma
  • Hodgkin Lymphoma
  • Myeloma

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Northside Hospital

    Atlanta, Georgia, 30342

Other trials in United States

About this study

Official title: A Phase II Trial of Post-Transplant Cyclophosphamide and Sirolimus for Graft-versus-host Disease (GVHD) Prophylaxis Following Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation

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.

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
Medical subject headings
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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    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.

Study groups in NCT01244906
Study groupRoleWhat they receive
Reduced Intensity Allogeneic Stem Cell TransplantationExperimentalAll 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.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 1 year

Secondary outcomes (5)

  1. Incidence of Absolute Neutrophil Count (ANC)/Platelet Engraftment

    To estimate the incidence of neutrophil and platelet engraftment

    Measured: Approximately Day 30

  2. Number of Participants With Non-Relapse Mortality

    Measured: 1 year

  3. Number of Patients With Disease Free Survival at 2 Years

    Measured: 2 years

  4. Number of Patients to Achieve Full Donor Chimerism

    Characterize rate of achievement of full donor chimerism

    Measured: 1 year

  5. Number of Patients With Overall Survival at 2 Years.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2010 (estimated)
  2. Study startDec 2010
  3. Primary completionApr 2014
  4. Study completionDec 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01244906
Sponsor's protocol ID
NSH 911
Status last verified
Jan 2015
First submitted
18 Nov 2010
Last updated
1 May 2015
Data monitoring committee
No

Publications

  • Szydlo R, Goldman JM, Klein JP, Gale RP, Ash RC, Bach FH, Bradley BA, Casper JT, Flomenberg N, Gajewski JL, Gluckman E, Henslee-Downey PJ, Hows JM, Jacobsen N, Kolb HJ, Lowenberg B, Masaoka T, Rowlings PA, Sondel PM, van Bekkum DW, van Rood JJ, Vowels MR, Zhang MJ, Horowitz MM. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997 May;15(5):1767-77. doi: 10.1200/JCO.1997.15.5.1767.

    PubMed 9164184

  • de Witte T, Brand R, van Biezen A, Mufti G, Ruutu T, Finke J, von dem Borne P, Vitek A, Delforge M, Alessandrino P, Harlahakis N, Russell N, Martino R, Verdonck L, Kroger N, Niederwieser D; European Blood and Marrow Transplantation Group (EBMT), Chronic Leukemia Working Party (CLWP)-MDS subcommittee. Allogeneic stem cell transplantation for patients with refractory anaemia with matched related and unrelated donors: delay of the transplant is associated with inferior survival. Br J Haematol. 2009 Sep;146(6):627-36. doi: 10.1111/j.1365-2141.2009.07809.x. Epub 2009 Jul 14.

    PubMed 19604243

  • 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.

    PubMed 19151786

  • Mielcarek M, Storer BE, Sandmaier BM, Sorror ML, Maloney DG, Petersdorf E, Martin PJ, Storb R. Comparable outcomes after nonmyeloablative hematopoietic cell transplantation with unrelated and related donors. Biol Blood Marrow Transplant. 2007 Dec;13(12):1499-507. doi: 10.1016/j.bbmt.2007.09.004.

    PubMed 18022580

  • Taylor PA, Lees CJ, Blazar BR. The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality. Blood. 2002 May 15;99(10):3493-9. doi: 10.1182/blood.v99.10.3493.

    PubMed 11986199

  • Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, Negrin RS. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003 Sep;9(9):1144-50. doi: 10.1038/nm915. Epub 2003 Aug 17.

    PubMed 12925844

  • 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.

    PubMed 14660744

  • Zhao D, Zhang C, Yi T, Lin CL, Todorov I, Kandeel F, Forman S, Zeng D. In vivo-activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic graft-versus-host disease. Blood. 2008 Sep 1;112(5):2129-38. doi: 10.1182/blood-2008-02-140277. Epub 2008 Jun 12.

    PubMed 18550852

  • 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.

    PubMed 15972448

  • 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.

    PubMed 16278306

  • Rezvani K, Mielke S, Ahmadzadeh M, Kilical Y, Savani BN, Zeilah J, Keyvanfar K, Montero A, Hensel N, Kurlander R, Barrett AJ. High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT. Blood. 2006 Aug 15;108(4):1291-7. doi: 10.1182/blood-2006-02-003996. Epub 2006 Apr 20.

    PubMed 16627754

  • Coenen JJ, Koenen HJ, van Rijssen E, Kasran A, Boon L, Hilbrands LB, Joosten I. Rapamycin, not cyclosporine, permits thymic generation and peripheral preservation of CD4+ CD25+ FoxP3+ T cells. Bone Marrow Transplant. 2007 May;39(9):537-45. doi: 10.1038/sj.bmt.1705628. Epub 2007 Mar 12.

    PubMed 17351648

  • Zeiser R, Nguyen VH, Beilhack A, Buess M, Schulz S, Baker J, Contag CH, Negrin RS. Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood. 2006 Jul 1;108(1):390-9. doi: 10.1182/blood-2006-01-0329. Epub 2006 Mar 7.

    PubMed 16522809

  • Lehnert S, Rybka WB. Amplification of the graft-versus-host reaction by cyclophosphamide: dependence on timing of drug administration. Bone Marrow Transplant. 1994 Apr;13(4):473-7.

    PubMed 8019473

  • Mayumi H. [Cyclophosphamide-induced immunological tolerance: an overview]. Nihon Geka Gakkai Zasshi. 1996 Dec;97(12):1097-108. Japanese.

    PubMed 9032788

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation in people with Hematologic Neoplasms, run by Northside Hospital, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of GVHD (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01244906, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2015.

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