Comparing ATG or Post-Transplant Cyclophosphamide to Calcineurin Inhibitor-Methotrexate as GVHD Prophylaxis After Myeloablative Unrelated Donor Peripheral Blood Stem Cell Transplantation

NCT03602898 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: 9954NCI-2018-01302RG1001747
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well 3 different drug combinations prevent graft versus host disease (GVHD) after donor stem cell transplant. Calcineurin inhibitors, such as cyclosporine and tacrolimus, may stop the activity of donor cells that can cause GVHD. Chemotherapy drugs, such as cyclophosphamide and methotrexate, may also stop the donor cells that can lead to GVHD while not affecting the cancer-fighting donor cells. Immunosuppressive therapy, such as anti-thymocyte globulin (ATG), is used to decrease the body's immune response and reduces the risk of GVHD. It is not yet known which combination of drugs: 1) ATG, methotrexate, and calcineurin inhibitor 2) cyclophosphamide and calcineurin inhibitor, or 3) methotrexate and calcineurin inhibitor may work best to prevent graft versus host disease and result in best overall outcome after donor stem cell transplant.

Conditions

Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematopoietic and Lymphoid System Neoplasm; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Recurrent Acute Myeloid Leukemia; Recurrent Hodgkin Lymphoma; Recurrent Non-Hodgkin Lymphoma; Refractory Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Moderate to severe chronic graft versus host disease (GVHD) based on National Institute of Health 2014 consensus criteria

  Probabilities of chronic GVHD at one year will be compared using a chi-square test.

  At 1 year

Secondary Outcomes (7)

• Survival

  At 1 year post transplant

• GVHD-free relapse-free survival (GRFS)

  At 1 year post transplant

• Chronic GVHD-free relapse-free survival (CRFS)

  At 1 year post transplant

• Grade II-IV acute GVHD

  At 100 days

• Grade III-IV acute GVHD

  At 100 days

Study Arms (3)

Arm 1 (ATG, tacrolimus or cyclosporine, methotrexate)

EXPERIMENTAL

Participants receive conditioning regimen (see detailed description) and then undergo peripheral blood stem cell transplantation on day 0. Participants receive anti-thymocyte globulin IV over 4-6 hours on days -3 to -1. Beginning day -1, participants also receive tacrolimus IV or cyclosporine IV BID tapered at day 50, and methotrexate IV on days 1, 3, 6 and 11 in the absence of disease progression or unacceptable toxicity.

Biological: Anti-Thymocyte Globulin; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Drug: Methotrexate; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Tacrolimus; Radiation: Total-Body Irradiation

Arm 2 (cyclophosphamide, tacrolimus or cyclosporine)

EXPERIMENTAL

Participants receive conditioning regimen (see detailed description) and then undergo peripheral blood stem cell transplantation on day 0. Participants receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Beginning day 5, participants also receive tacrolimus IV or cyclosporine IV BID tapered at day 50 in the absence of disease progression or unacceptable toxicity.

Drug: Busulfan; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Tacrolimus; Radiation: Total-Body Irradiation

Arm 3 (tacrolimus or cyclosporine, methotrexate)

EXPERIMENTAL

Participants receive conditioning regimen (see detailed description) and then undergo peripheral blood stem cell transplantation on day 0. Beginning day -1, participants receive tacrolimus IV or cyclosporine IV BID tapered at day 50, and methotrexate IV on days 1, 3, 6 and 11.

Drug: Busulfan; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Drug: Methotrexate; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Tacrolimus; Radiation: Total-Body Irradiation

Interventions

Anti-Thymocyte Globulin BIOLOGICAL

Given IV

Also known as: Antithymocyte Globulin, Antithymocyte Serum, ATG, ATS

Arm 1 (ATG, tacrolimus or cyclosporine, methotrexate)

Busulfan DRUG

Given IV or PO

Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

Arm 1 (ATG, tacrolimus or cyclosporine, methotrexate); Arm 2 (cyclophosphamide, tacrolimus or cyclosporine); Arm 3 (tacrolimus or cyclosporine, methotrexate)

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 1 (ATG, tacrolimus or cyclosporine, methotrexate); Arm 2 (cyclophosphamide, tacrolimus or cyclosporine); Arm 3 (tacrolimus or cyclosporine, methotrexate)

Cyclosporine DRUG

Given IV or PO

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

Arm 1 (ATG, tacrolimus or cyclosporine, methotrexate); Arm 2 (cyclophosphamide, tacrolimus or cyclosporine); Arm 3 (tacrolimus or cyclosporine, methotrexate)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Arm 1 (ATG, tacrolimus or cyclosporine, methotrexate); Arm 2 (cyclophosphamide, tacrolimus or cyclosporine); Arm 3 (tacrolimus or cyclosporine, methotrexate)

Methotrexate DRUG

Given IV

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Arm 1 (ATG, tacrolimus or cyclosporine, methotrexate); Arm 3 (tacrolimus or cyclosporine, methotrexate)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo peripheral blood stem cell transplantation

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Arm 1 (ATG, tacrolimus or cyclosporine, methotrexate); Arm 2 (cyclophosphamide, tacrolimus or cyclosporine); Arm 3 (tacrolimus or cyclosporine, methotrexate)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm 1 (ATG, tacrolimus or cyclosporine, methotrexate); Arm 2 (cyclophosphamide, tacrolimus or cyclosporine); Arm 3 (tacrolimus or cyclosporine, methotrexate)

Questionnaire Administration OTHER

Ancillary studies

Arm 1 (ATG, tacrolimus or cyclosporine, methotrexate); Arm 2 (cyclophosphamide, tacrolimus or cyclosporine); Arm 3 (tacrolimus or cyclosporine, methotrexate)

Tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Arm 1 (ATG, tacrolimus or cyclosporine, methotrexate); Arm 2 (cyclophosphamide, tacrolimus or cyclosporine); Arm 3 (tacrolimus or cyclosporine, methotrexate)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: Total Body Irradiation, whole body irradiation, Whole-Body Irradiation, TBI

Arm 1 (ATG, tacrolimus or cyclosporine, methotrexate); Arm 2 (cyclophosphamide, tacrolimus or cyclosporine); Arm 3 (tacrolimus or cyclosporine, methotrexate)

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The following diseases will be permitted, although other diagnoses can be considered if approved by Fred Hutch Patient Care Conference or the participating institution's patient review committees and the principal investigator:
• Acute lymphocytic leukemia (ALL) in complete remission (CR)1 with high risk features defined as evidence of adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or MLL rearrangements or presence of minimal residual disease
• Acute myeloid leukemia (AML) in CR1 with high risk features defined as:
• Intermediate or adverse risk disease as defined by European LeukemiaNet (ELN) 2017
• Greater than 1 cycle of induction therapy required to achieve remission
• Preceding myelodysplastic syndrome (MDS) or myelofibrosis
• Therapy-related AML
• Presence of FLT3 internal tandem duplications
• French-American-British (FAB) M6 or M7 classification
• Acute leukemia (ALL or AML) in second (2nd) or greater CR (CR ≥ 2)
• Refractory or relapsed AML with =\< 5% bone marrow blasts and no circulating blasts by morphology or proven extramedullary disease
• Myelodysplastic syndrome (MDS) with following high risk features: poor cytogenetics (-7, inv(3)/t(3q)/del(3q), del(7q) or complex cytogenetics defined as \>= 3 abnormalities), Revised International Prognostic Scoring System (IPSS-R) risk group intermediate or higher, or treatment-related MDS
• Any phase of MDS if patient is \< 21 years of age
• Chronic myelogenous leukemia (CML) beyond 1st chronic phase or resistant to tyrosine kinase inhibitors (adults)
• Chronic myelomonocytic leukemia (CMML)

You may not qualify if:

• Prior autologous or allogeneic stem cell transplant
• Performance status: Karnofsky score \<60 or Lansky score \<50 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-lymphotropic virus (HTLV)-1, 2
• Left ventricular ejection fraction \< 45%. Uncontrolled arrhythmias or symptomatic cardiac disease
• Symptomatic pulmonary disease. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO) =\< 50% of predicted (corrected for hemoglobin). Use of continuous supplemental oxygen
• Calculated (Cockroft-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
• History of allergy or anaphylactic reaction to rabbit protein or to any product excipients
• Subjects may not be enrolled in other investigational trials with acute or chronic GVHD as the primary endpoint
• Donor who will exclusively donate marrow
• Donors who are HIV-positive
• Potential donors who for psychological, physiological, or medical reasons cannot tolerate administration of G-CSF or apheresis
• Donors who are allergic to filgrastim or Escherichia (E.) coli-derived proteins

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Chronic-Phase; Myelodysplastic Syndromes; Primary Myelofibrosis; Myeloproliferative Disorders; Leukemia, Myeloid, Acute; Hodgkin Disease; Lymphoma, Non-Hodgkin

Interventions

Antilymphocyte Serum; Busulfan; Cyclophosphamide; Cyclosporine; Cyclosporins; fludarabine phosphate; Methotrexate; merphos; Peripheral Blood Stem Cell Transplantation; Tacrolimus; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Macrolides; Lactones; Radiotherapy; Investigative Techniques

Study Officials

• Masumi Ueda Oshima

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: July 27, 2018
• Study Start: June 1, 2021
• Primary Completion: September 17, 2023
• Study Completion: September 17, 2023
• Last Updated: June 30, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)