- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03602898
Comparing ATG or Post-Transplant Cyclophosphamide to Calcineurin Inhibitor-Methotrexate as GVHD Prophylaxis After Myeloablative Unrelated Donor Peripheral Blood Stem Cell Transplantation
A Randomized Phase II Study to Compare ATG or Post-Transplant Cyclophosphamide to Calcineurin Inhibitor-Methotrexate as GVHD Prophylaxis After Myeloablative Unrelated Donor Peripheral Blood Stem Cell Transplantation
Study Overview
Status
Conditions
- Recurrent Hodgkin Lymphoma
- Myelofibrosis
- Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
- Chronic Myelomonocytic Leukemia
- Myelodysplastic Syndrome
- Recurrent Acute Myeloid Leukemia
- Refractory Acute Myeloid Leukemia
- Hematopoietic and Lymphoid System Neoplasm
- Recurrent Non-Hodgkin Lymphoma
- Myeloproliferative Neoplasm
- Therapy-Related Acute Myeloid Leukemia
- Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Acute Lymphoblastic Leukemia in Remission
Intervention / Treatment
- Other: Quality-of-Life Assessment
- Other: Questionnaire Administration
- Drug: Cyclophosphamide
- Drug: Methotrexate
- Radiation: Total-Body Irradiation
- Biological: Anti-Thymocyte Globulin
- Drug: Fludarabine Phosphate
- Drug: Tacrolimus
- Drug: Cyclosporine
- Drug: Busulfan
- Procedure: Peripheral Blood Stem Cell Transplantation
Detailed Description
OUTLINE:
CONDITIONING REGIMENS: Participants receive 1 of 3 regimens and are randomized to 1 of 3 arms for GVHD prophylaxis.
REGIMEN A: Participants undergo total body irradiation (TBI) twice daily (BID) on days -6 to -4 (-7 to -4 for those < 18 years), then receive cyclophosphamide IV over 1-2 hours on days -3 and -2. Participants randomized to Arm 2 only receive TBI on days -3 to -1 (-4 to -1 for those < 18 years).
REGIMEN B: Participants receive fludarabine phosphate IV and busulfan IV every 6 hours on days -5 to -2.
REGIMEN C: Participants receive busulfan orally (PO) or IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 1-2 hours on days -3 and -2.
Myelofibrosis or other myeloproliferative neoplasms: Participants >= 18 years receive cyclophosphamide IV over 1-2 hours on days -7 and -6 and busulfan IV on days -5 to -2. Participants < 17 years receive busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2.
All participants undergo peripheral blood stem cell transplantation on day 0.
ARM 1: 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 twice daily (BID) tapered at day 50, and methotrexate IV on days 1, 3, 6 and 11 in the absence of disease progression or unacceptable toxicity.
ARM 2: 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.
ARM 3: 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 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up at 6 months, then annually up to 5 years.
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutch/University of Washington Cancer Consortium
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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)
- Myeloproliferative disorders/myelofibrosis
- Hodgkin or non-Hodgkin lymphoma: relapsed chemotherapy-sensitive (complete or partial response)
- Female patients must have negative standard pregnancy test (all women of child bearing-potential must have test performed)
- Ability to understand and the willingness to sign a written informed consent document
- For patients with acute leukemia, CR is defined as =< 5% marrow blasts by morphology. CR with incomplete count recovery is allowed
- DONOR INCLUSION
- Unrelated donors matched for human leukocyte antigen (HLA)-A, B, C, DRB1 and DQB1 by high resolution typing
- Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment. This determination is based on the standard practice of the individual institution. The recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before hematopoietic cell transplantation (HCT). If the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained. The donor should be excluded if any of the cytotoxic cross match assays are positive
- Only granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cell (PBSC) will be permitted as a hematopoietic stem cell (HSC) source on this protocol
- Donors must meet the selection criteria for administration of G-CSF and apheresis defined based on each institution's standard practice protocol for unrelated donors
- Donors must be capable of giving informed consent
Exclusion Criteria:
- 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 EXCLUSION
- 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
- Donor-related risks to recipients
- Positive anti-donor lymphocytotoxic crossmatch
- Pregnant or lactating women
- Prior malignancy within the last 5 years
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Arm 1 (ATG, tacrolimus or cyclosporine, methotrexate)
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.
|
Ancillary studies
Other Names:
Ancillary studies
Given IV
Other Names:
Given IV
Other Names:
Undergo TBI
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
Given IV or PO
Other Names:
Given IV or PO
Other Names:
Undergo peripheral blood stem cell transplantation
Other Names:
|
EXPERIMENTAL: Arm 2 (cyclophosphamide, tacrolimus or cyclosporine)
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.
|
Ancillary studies
Other Names:
Ancillary studies
Given IV
Other Names:
Undergo TBI
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
Given IV or PO
Other Names:
Given IV or PO
Other Names:
Undergo peripheral blood stem cell transplantation
Other Names:
|
EXPERIMENTAL: Arm 3 (tacrolimus or cyclosporine, methotrexate)
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.
|
Ancillary studies
Other Names:
Ancillary studies
Given IV
Other Names:
Given IV
Other Names:
Undergo TBI
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
Given IV or PO
Other Names:
Given IV or PO
Other Names:
Undergo peripheral blood stem cell transplantation
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Moderate to severe chronic graft versus host disease (GVHD) based on National Institute of Health 2014 consensus criteria
Time Frame: At 1 year
|
Probabilities of chronic GVHD at one year will be compared using a chi-square test.
|
At 1 year
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Survival
Time Frame: At 1 year post transplant
|
At 1 year post transplant
|
GVHD-free relapse-free survival (GRFS)
Time Frame: At 1 year post transplant
|
At 1 year post transplant
|
Chronic GVHD-free relapse-free survival (CRFS)
Time Frame: At 1 year post transplant
|
At 1 year post transplant
|
Grade II-IV acute GVHD
Time Frame: At 100 days
|
At 100 days
|
Grade III-IV acute GVHD
Time Frame: At 100 days
|
At 100 days
|
Relapse
Time Frame: At 1 year post transplant
|
At 1 year post transplant
|
Non-relapse mortality
Time Frame: At 1 year post transplant
|
At 1 year post transplant
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Precancerous Conditions
- Myelodysplastic-Myeloproliferative Diseases
- Leukemia, Lymphoid
- Neoplasms
- Lymphoma
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Recurrence
- Preleukemia
- Leukemia, Myelomonocytic, Chronic
- Leukemia, Myelomonocytic, Juvenile
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Leukemia, Myeloid, Chronic-Phase
- Myeloproliferative Disorders
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dermatologic Agents
- Antifungal Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Calcineurin Inhibitors
- Cyclophosphamide
- Fludarabine
- Fludarabine phosphate
- Methotrexate
- Tacrolimus
- Busulfan
- Antilymphocyte Serum
- Cyclosporine
- Cyclosporins
Other Study ID Numbers
- 9954 (OTHER: Fred Hutch/University of Washington Cancer Consortium)
- NCI-2018-01302 (REGISTRY: CTRP (Clinical Trial Reporting Program))
- RG1001747 (OTHER: Fred Hutch/University of Washington Cancer Consortium)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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