Comparison of Triple GVHD Prophylaxis Regimens for Nonmyeloablative or Reduced Intensity Conditioning Unrelated Mobilized Blood Cell Transplantation

NCT03246906 | Terminated Phase 2 Results DMC FDA Drug

• 5 other identifiers: 9816NCI-2017-01311P01CA078902P30CA015704RG9217021
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase II trial includes a blood stem cell transplant from an unrelated donor to treat blood cancer. The treatment also includes chemotherapy drugs, but in lower doses than conventional (standard) stem cell transplants. The researchers will compare two different drug combinations used to reduce the risk of a common but serious complication called "graft versus host disease" (GVHD) following the transplant. Two drugs, cyclosporine (CSP) and sirolimus (SIR), will be combined with either mycophenolate mofetil (MMF) or post-transplant cyclophosphamide (PTCy). This part of the transplant procedure is the main research focus of the study.

Conditions

Myelodysplastic/Myeloproliferative Neoplasm; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Diffuse Large B-Cell Lymphoma; Mantle Cell Lymphoma; Myelodysplastic Syndrome; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Hodgkin Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Hematologic and Lymphocytic Disorder; Blastic Plasmacytoid Dendritic Cell Neoplasm

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Chronic Graft Versus Host Disease (GVHD)-Free, Relapse-free Survival (CRFS)

  Composite time-to-event outcome in which events include moderate or severe chronic GVHD based on National Institute of Health consensus criteria, relapse, or death from any cause.

  At 1 year post- hematopoietic cell transplantation (HCT)

Secondary Outcomes (8)

• Number of Patients With Grades II-IV Acute Graft Versus Host Disease (GVHD)

  At day 100 post-HCT

• Number of Patients With Grades III-IV Acute Graft Versus Host Disease (GVHD)

  At day 100 post-HCT

• Number of Patients With Late Graft Versus Host Disease (GVHD) Not Meeting National Institute of Health (NIH) Consensus Criteria for Chronic GVHD

  At 1 year post-HCT

• Number of Patients With Moderate and Severe Chronic Graft Versus Host Disease

  At 1 year post-HCT

• Number of Patients With Relapse/Progression

  At 1 year post-HCT

Study Arms (2)

Arm I (mycophenolate mofetil, cyclosporine, sirolimus)

EXPERIMENTAL

Patients undergo allogeneic HCT at day 0. Patients with an HLA-matched unrelated donor receive mycophenolate mofetil PO on days 0 to 40, cyclosporine PO every 12 hours BID on days -3 to 96 then tapered to day 150, and sirolimus PO QD on days -3 to day 150 then tapered to day 180. Patients with an HLA-mismatched donor receive mycophenolate mofetil PO on days 0-100 then tapered to day 150, cyclosporine PO BID on days -3 to 150 then tapered to day 180, and sirolimus PO QD on days -3 to 180 then tapered to day 365.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclosporine; Drug: Mycophenolate Mofetil; Drug: Sirolimus

Arm II (cyclosporine, sirolimus, cyclophosphamide)

EXPERIMENTAL

Patients undergo HCT at day 0. Patients with an HLA-matched unrelated donor receive cyclosporine PO BID on days 5-96 then tapered to day 150, sirolimus PO QD on days 5-150 then tapered to day 180, and cyclophosphamide IV on days 3 and 4. Patients with an HLA-mismatched donor receive cyclosporine PO BID on days 5-150 then tapered to day 180, sirolimus PO QD on days 5-180 then tapered to day 365, and cyclophosphamide IV on days 3 and 4.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Sirolimus

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo HCT

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

Arm I (mycophenolate mofetil, cyclosporine, sirolimus); Arm II (cyclosporine, sirolimus, cyclophosphamide)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Arm II (cyclosporine, sirolimus, cyclophosphamide)

Cyclosporine DRUG

Given PO

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya

Arm I (mycophenolate mofetil, cyclosporine, sirolimus); Arm II (cyclosporine, sirolimus, cyclophosphamide)

Mycophenolate Mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Arm I (mycophenolate mofetil, cyclosporine, sirolimus)

Sirolimus DRUG

Given PO

Also known as: AY 22989, RAPA, Rapamune, Rapamycin, SILA 9268A, WY-090217

Arm I (mycophenolate mofetil, cyclosporine, sirolimus); Arm II (cyclosporine, sirolimus, cyclophosphamide)

Eligibility Criteria

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

You may qualify if:

• Ages \> 50 years with hematologic malignancies treatable by unrelated hematopoietic cell transplant (HCT)
• Ages 18-50 years with hematologic diseases treatable by allogeneic HCT who through pre-existing medical conditions or prior therapy are considered to be at high risk for regimen related toxicity associated with a high dose transplant
• Ages 18-50 years with chronic lymphocytic leukemia (CLL)
• The following diseases will be permitted although other diagnoses can be considered if approved by PCC and the principal investigator.
• Aggressive non-Hodgkin lymphomas (NHL) and other histologies such as diffuse large B cell NHL- not eligible for autologous HCT, not eligible for high-dose allogeneic HCT, or after failed autologous HCT
• Mantle cell NHL - may be treated in first complete remission (CR); (diagnostic lumbar puncture \[LP\] required pre-transplant)
• Low grade NHL - with \< 6 month duration of CR between courses of conventional therapy
• CLL - must have either 1) failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (FLU) (or another nucleoside analog, e.g. cladribine \[2-CDA\], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog); 2) failed FLU-cyclophosphamide (CY)-rituximab (FCR) combination chemotherapy at any time point; or 3) have "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR; or 4) patients with a diagnosis of CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL; 5) patients failing to achieve a response to ibrutinib as first-line therapy; 6) patients not responding to ibrutinib, idelalisib, or venetoclax as salvage therapy or intolerant of these agents as salvage therapy due to side effects; all CLL patients must have received prior myelosuppressive chemotherapy
• Hodgkin lymphoma - must have received and failed frontline therapy
• Multiple myeloma - must have received prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative HCT is permitted
• Acute myeloid leukemia (AML) - must have \< 5% marrow blasts at the time of transplant
• Acute lymphocytic leukemia (ALL) - must have \< 5% marrow blasts at the time of transplant
• Chronic myeloid leukemia (CML) - patients in CP1 must have failed or be intolerant of tyrosine kinase inhibitors (TKIs); patients beyond CP1 will be accepted if they have \< 5% marrow blasts at time of transplant
• Myelodysplasia (MDS)/myeloproliferative syndrome (MPS)/chronic myelomonocytic leukemia (CMML) - patients must have \< 5% marrow blasts at time of transplant
• Waldenstrom's macroglobulinemia - must have failed 2 courses of therapy

You may not qualify if:

• Patients with rapidly progressive intermediate or high grade NHL
• Patients with a diagnosis of chronic myelomonocytic leukemia (CMML) who have not received induction chemotherapy
• Patients with MDS-EB or AML who have not received myelosuppressive chemotherapy i.e. induction chemotherapy or at least 4 cycles of a venetoclax-containing regimen will be excluded from Regimen B conditioning (Fludarabine and total body irradiation \[TBI\])
• CNS involvement with disease refractory to intrathecal chemotherapy
• Presence of circulating blasts determined to be associated with disease (in the blood) for patients with AML, ALL or CML
• Presence of \>= 5% circulating leukemic blasts (in the blood) detected by standard pathology for patients with MDS/MPS/CMML
• Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
• Females who are pregnant or breast-feeding
• Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
• Organ dysfunction
• Cardiac ejection fraction \< 35% (or, if unable to obtain ejection fraction, shortening fraction of \< 26%); ejection fraction is required if age \> 50 years or there is a history of anthracycline exposure or history of cardiac disease; patients with a shortening fraction \< 26% may be enrolled if approved by a cardiologist
• Pulmonary:
• \*\* Diffusing capacity of the lungs for carbon monoxide (DLCO) \< 40%, forced expiratory volume in the first second of breath (FEV1) \< 40% and/or receiving supplementary continuous oxygen; when pulmonary function tests (PFTs) cannot be obtained, the 6-minute walk test (6MWT, also known as exercise oximetry) will be used: Any patient with oxygen saturation on room air of \< 89% during a 6MWT will be excluded
• The FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules
• Liver function abnormalities: Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3 mg/dL, or symptomatic biliary disease

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Ueda Oshima M, Vo PT, Boeckh M, Bouvier ME, Carpenter PA, Mielcarek M, Petersdorf EW, Storb R, Gooley T, Sandmaier BM. Sirolimus and Cyclosporine With Post-Transplant Cyclophosphamide or Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis in Unrelated Donor Hematopoietic Cell Transplantation. J Clin Oncol. 2025 Nov 20;43(33):3600-3609. doi: 10.1200/JCO-25-01238. Epub 2025 Oct 3.

  PMID: 41043099 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Prolymphocytic; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hodgkin Disease; Multiple Myeloma; Waldenstrom Macroglobulinemia; Hematologic Diseases; Blastic Plasmacytoid Dendritic Cell Neoplasm

Interventions

Cyclophosphamide; Cyclosporine; Cyclosporins; Mycophenolic Acid; Sirolimus

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Bone Marrow Diseases; Myeloproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Histiocytic Disorders, Malignant; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones

Results Point of Contact

• Title: Dr. Masumi Ueda Oshima
• Organization: Fred Hutch Cancer Center

mueda@fredhutch.org

(206) 667-4546

Study Officials

• Masumi Ueda Oshima

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 8, 2017
• First Posted: August 11, 2017
• Study Start: September 11, 2017
• Primary Completion: May 3, 2025
• Study Completion: May 3, 2025
• Last Updated: May 14, 2026
• Results First Posted: May 14, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)