Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies
A Phase II Study to Evaluate the Efficacy of Posttransplant Cyclophosphamide for Prevention of Chronic Graft-versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation
3 other identifiers
interventional
43
1 country
1
Brief Summary
This phase II trial studies how well cyclophosphamide works in preventing chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplant in patients with hematological malignancies. Giving chemotherapy and total-body irradiation before transplantation helps stop the growth of cancer cells and prevents the patient's immune system from rejecting the donor's stem cells. Healthy stem cells from a donor that are infused into the patient help the patient's bone marrow make blood cells; red blood cells, white blood cells, and platelets. Sometimes, however, the transplanted donor cells can cause an immune response against the body's normal cells, which is called graft-versus-host disease (GVHD). Giving cyclophosphamide after transplant may prevent this from happening or may make chronic GVHD less severe.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Sep 2011
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 31, 2011
CompletedStudy Start
First participant enrolled
September 1, 2011
CompletedFirst Posted
Study publicly available on registry
September 2, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2015
CompletedResults Posted
Study results publicly available
May 19, 2017
CompletedMay 19, 2017
May 1, 2017
2.8 years
August 31, 2011
April 11, 2017
May 17, 2017
Conditions
Outcome Measures
Primary Outcomes (1)
Chronic GVHD Requiring Systemic Immunosuppressive Treatment
Chronic GVHD will be defined by National Institutes of Health (NIH) criteria and requiring systemic treatment. A reduction in the cumulative incidence of GVHD from \~35% to \~15% at 1 year would represent a reasonable goal. A sample size of 42 patients provides 90% power to observe such a difference with one-side 5% type-1 error.
At 1 year after transplantation
Secondary Outcomes (9)
Donor Engraftment
At day 28
Grades II-IV and III-IV Acute GVHD
Through day +100 post-transplant
Duration of Systemic Immunosuppressive Treatment
Up to 5 years
Persistent or Recurrent Malignancy After HCT
At 2 years
Non-relapse Mortality
At 2 years
- +4 more secondary outcomes
Study Arms (1)
Treatment (TBI, PBSCT, and cyclophosphamide GVHD prophylaxis)
EXPERIMENTALPREPARATIVE REGIMEN: Patients receive TBI BID on days -4 or -3 to -1. Some patients also receive fludarabine IV daily on days -5 to -2 and busulfan IV over 3 hours QD or over 2 hours every 6 hours on days -5 to -2. Patients may also undergo CNS prophylaxis, testicular irradiation, and/or involved field irradiation as per standard practice. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0 per standard practice. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4. Patients also receive cyclosporine IV every 12 hours or every 8 hours beginning on day 5 with taper on days 56-126.
Interventions
Given IV
Given IV
Undergo allogeneic PBSCT
Undergo TBI
Given IV
Given IV
Undergo allogeneic PBSCT
Eligibility Criteria
You may qualify if:
- Acute lymphocytic leukemia (ALL) in morphologic first complete remission (CR1) with high risk features defined as, but not limited to: evidence of adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or mixed-lineage leukemia (MLL) rearrangements; presence of minimal residual disease; progenitor B-cell immunophenotype; high white blood cells (WBC) at diagnosis (\> 30,000/ul in B-ALL; \> 100,000/ul in T-ALL); or delayed attainment of CR (\> 4 weeks) after induction therapy; additional clinical characteristics deemed to confer a high relapse risk may be discussed with and approved by the Principal Investigator (PI)
- Acute myeloid leukemia (AML) in CR1 EXCEPT patients with low-risk features defined as:
- Inv 16 or t(8;21) in the absence of c-kit mutations
- Normal karyotype who are FLT3-ITD-negative and NPM1-positive in the absence of c-kit mutations
- Patients with respective "low-risk" features are eligible, however, if (i) more than 1 cycle of induction therapy was required to achieve CR1 (ii) the patient had a preceding myelodysplastic syndrome (MDS) other than myelofibrosis, or (iii) secondary AML
- Acute leukemia in 2nd or greater CR (CR \>= 2)
- Refractory or relapsed AML with =\< 10% bone marrow blasts and no circulating blasts or proven extramedullary disease
- AML transformed from myelodysplastic syndrome (MDS) with \< 10% bone marrow blasts
- MDS with following high risk features:
- High risk cytogenetics (including, but not limited to: 7q--, inv\[3\], t\[3q\], del\[3q\] or complex karyotype)
- International Prognostic Scoring System (IPSS) intermediate (INT)-2 or greater
- Treatment-related MDS
- Any phase of MDS if patient is \< 21 years of age
- Chronic myelogenous leukemia (CML) beyond 1st chronic phase or resistant or intolerant to tyrosine kinase inhibitors (adults) or any phase (pediatric \< 21 years)
- Chronic myelomonocytic leukemia
- +7 more criteria
You may not qualify if:
- Prior autologous or allogeneic stem cell transplant
- Performance status \> 2 (Eastern Cooperative Oncology Group \[ECOG\]) or \< 50 (Lansky; for patients \< 16 years old)
- Uncontrolled infection; the protocol principal investigator (PI) will be final arbiter if there is uncertainty regarding whether a previous infection is under adequate control to allow enrollment in the study
- Positive serology for human immunodeficiency virus (HIV)-1, 2 or human T cell lymphotropic virus (HTLV)-1, 2
- Left ventricular ejection fraction \< 45% or shortening fraction \< 25%; no uncontrolled arrhythmias or symptomatic cardiac disease
- Symptomatic pulmonary disease; forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO) =\< 50% of predicted (corrected for hemoglobin); if pulmonary function tests cannot be performed, an oxygen saturation \< 92% on room air
- Calculated (Cockcroft-Gault or appropriate calculation for pediatric patients) serum creatinine clearance =\< 60 mL/min; if the calculated CrCl is 50-60 mL/min, but a measured CrCl by 24 hour urine collection is \> 60 mL/min, this measurement is acceptable
- Total serum bilirubin more than twice upper normal limit
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 3-fold higher than laboratory upper normal limits
- Female patient must have negative serum pregnancy test (all women of child bearing-potential must have test performed)
- DONORS: Potential donors who for psychological, physiological, or medical reasons cannot tolerate administration of G-CSF or apheresis
- DONORS: Donors who are allergic to filgrastim or Escherichia (E.) coli-derived proteins
- DONORS: Donor-related risks to recipients
- DONORS: Positive anti-donor lymphocytotoxic crossmatch
- DONORS: Donors who are positive for HIV
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
Related Publications (1)
Mielcarek M, Furlong T, O'Donnell PV, Storer BE, McCune JS, Storb R, Carpenter PA, Flowers ME, Appelbaum FR, Martin PJ. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016 Mar 17;127(11):1502-8. doi: 10.1182/blood-2015-10-672071. Epub 2016 Jan 13.
PMID: 26764356DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Marco Mielcarek, MD
- Organization
- Fred Hutchinson Cancer Research Center
Study Officials
- PRINCIPAL INVESTIGATOR
Marco Mielcarek
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
August 31, 2011
First Posted
September 2, 2011
Study Start
September 1, 2011
Primary Completion
June 1, 2014
Study Completion
July 1, 2015
Last Updated
May 19, 2017
Results First Posted
May 19, 2017
Record last verified: 2017-05