- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03018223
Calcineurin Inhibitor-Free GVHD Prevention Regimen After Related Haplo PBSCT
September 14, 2021 updated by: H. Lee Moffitt Cancer Center and Research Institute
A Calcineurin Inhibitor-Free GVHD Prevention Regimen After Related Haploidentical Peripheral Blood Stem Cell Transplantation
The purpose of this study is to find out if a combination of drugs (these are called: cyclophosphamide, sirolimus, and mycophenolate mofetil) will protect participants better against graft vs. host disease (GVHD) after receiving a hematopoietic cell transplant from a related partially matched (haploidentical) donor.
As part of the treatment for their blood cancer, participants need a hematopoietic cell transplantation (HCT) to improve their chances of cure.
In any HCT, after the stem cell infusion is given, a combination of drugs is needed to prevent GVHD and facilitate acceptance of the graft.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
32
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Florida
-
Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center and Research Institute
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
Patient Participants:
- Age: Must be older than 18 years, no upper age limit.
- Karnofsky performance status: Full intensity conditioning, 80-100%; reduced intensity conditioning, 60-100%.
- Vital organ function: a) Cardiac: Left ventricular ejection fraction must be > 45% assessed by multigated acquisition (MUGA) scan or echocardiogram. No myocardial infarction within 6 months of transplant evaluation. b) Pulmonary: forced expiratory volume at one second (FEV1), forced vital capacity (FVC), and adjusted diffusing capacity of the lungs for carbon monoxide (DLCO) must be ≥ 50% of predicted values. c) Liver: Transaminases (AST, ALT) less than 2 times upper limit of normal values. d) Kidney: Estimated creatinine clearance ≥ 50 cc/min.
- Signed informed consent.
- Included disease conditions and remission status: a) Acute leukemia in First Complete Remission (CR1) or second/subsequent CR. b) Chronic myeloid leukemia, primary myelofibrosis, chronic myelomonocytic leukemia. c) Int-2 or high risk myelodysplastic syndrome (MDS). d) Hodgkin lymphoma beyond CR1 with chemosensitive disease, Stable Disease (SD) may be included if no mass >3 cm. e) Non-Hodgkin lymphoma in high risk CR1 or subsequent CR (by clinical, cytogenetic or molecular criteria), primary induction failure (PIF) or relapsed with chemosensitive disease. SD may be included if no mass >3 cm. f) Multiple myeloma in CR/Very Good Partial Response (VGPR).
Donor Participants:
- Per Moffitt Cancer Center (MCC) Blood and Marrow Transplant (BMT) program practices, an allele level matched (8/8 HLA A, B, C and DR) sibling or unrelated donor is preferred. If a matched donor is not found, mismatched unrelated or haploidentical donors may be considered.
- If a haploidentical donor is considered, parents, children, full siblings and in selected cases, extended family, will have high resolution typing at the MCC HLA laboratory. A familiar haploidentical donor is chosen among those who share at least one HLA-A, B, C, DRB1 and DQB1 haplotype with the patient.
- Patient will be screened for antibodies targeting mismatched HLA antigens in potential haploidentical donors (donor specific antibodies, DSA). Antibody screen and confirmatory testing using Luminex single antigen-bead test will be done.
- Among several potential donors, will choose in order of priority: a) Matched cytomegalovirus (CMV) immunoglobulin G (IgG) serologic status between donor and recipient. b) ABO blood group system-matched donor preferred, then minor ABO mismatch, then major ABO mismatch. c) Younger donor preferred: child, then sibling, and then parent. d) For male recipient, male donor will be preferred. Avoid mother as a donor unless no other choices.
Exclusion Criteria:
Patient Participants:
- Uncontrolled active bacterial, viral, fungal infection.
- Prior allogeneic HCT.
- Unwilling to comply with study requirements.
- Active, progressive or advanced disease based on diagnosis.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Conditioning/HCT/GVHD Prophylaxis
Pre-HCT Conditioning, HCT, GVHD Prophylaxis.
|
Myeloablative conditioning: 40 mg/m^2 daily for 4 days.
Dose will be adjusted for estimated creatinine clearance.
Reduced intensity conditioning: 30 mg/m^2 daily on days -6, -5, -4, -3 and -2.
Dose will be adjusted for estimated creatinine clearance.
Other Names:
Myeloablative conditioning: IV dosing targeted for a daily total area under curve (AUC) 5300 mmol*min/L for 4 days.
Busulfan AUC will be pharmacokinetically targeted.
An AUC 3500 mmol*min/l may be considered in patients over 60 years of age or with multiple comorbidities.
Chemotherapy may start on day -6 or day -5 depending on the day of admission (-6 for Wednesday admission, -5 for Sunday admission).
Other Names:
Reduced intensity conditioning: 14.5 mg/kg/day on days -6, -5.
GVHD prophylaxis: 50 mg/kg ideal body weight (IBW) daily dose will be given on days +3 and +4 post-transplant as an IV infusion over 1-2 hours.
Other Names:
Reduced intensity conditioning: 200 centigray (cGy) on day -1.
Other Names:
On day 0, patients will receive a peripheral blood hematopoietic cell graft.
Other Names:
GVHD prophylaxis: SIR will be administered as a 9 mg oral loading dose on day +5, followed by maintenance.
SIR levels will be monitored and maintenance dosing adjusted as needed for a target trough level 8 to 14 ng/ml, per Moffitt BMT program standard practice.
In the absence of acute GVHD, sirolimus taper will start on day +90 (+/- 10 days) and it is suggested to finish by day +180.
Other Names:
GVHD prophylaxis: MMF will start on day +5 at a dose of 15 mg/kg every 8 hours IV with the maximum daily dose not to exceed 3 gm.
MMF will be changed to orally (PO) and discontinued on day +35 (without taper) in the absence of acute GVHD.
Other Names:
Growth factor support: G-CSF will be given beginning on day 5 at a dose of 5 mcg/kg/day (rounding to the nearest vial dose), until absolute granulocyte count (ANC) is > 1,000/mm^3 for three consecutive days.
G-CSF may be given IV or subcutaneously.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Grade II-IV Acute Graft vs. Host Disease (GVHD)
Time Frame: 100 days post hematopoietic cell transplant (HCT)
|
Cumulative incidence of grade II-IV acute GVHD by day 100 after HCT.
Acute GVHD organ staging and assessment of overall grade will use standard consensus criteria.
The cumulative incidence of acute and chronic GVHD will be estimated, considering malignancy relapse and non-relapse death as competing risk events.
|
100 days post hematopoietic cell transplant (HCT)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Chronic GVHD
Time Frame: 1 year post HCT
|
Cumulative incidence of chronic GVHD by 1 year.
Chronic GVHD diagnosis follow National Institutes of Health (NIH) Consensus guidelines.
|
1 year post HCT
|
Overall Survival (OS)
Time Frame: Up to 1 year post HCT
|
Overall survival is defined as time from transplant to death or last follow-up, and is reported as percentage of surviving participants.
|
Up to 1 year post HCT
|
Progression Free Survival (PFS)
Time Frame: Up to 1 year post HCT
|
Progression-free survival defined by the time interval from transplant to relapse/recurrence, to death or to last follow-up.
Reported as percentage of participants who are disease free one year post HCT.
|
Up to 1 year post HCT
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Nelli Bejanyan, M.D., H. Lee Moffitt Cancer Center and Research Institute
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 31, 2017
Primary Completion (Actual)
December 15, 2018
Study Completion (Actual)
March 18, 2021
Study Registration Dates
First Submitted
January 10, 2017
First Submitted That Met QC Criteria
January 10, 2017
First Posted (Estimate)
January 11, 2017
Study Record Updates
Last Update Posted (Actual)
September 16, 2021
Last Update Submitted That Met QC Criteria
September 14, 2021
Last Verified
September 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Bone Marrow Diseases
- Hematologic Diseases
- Hemorrhagic Disorders
- Myeloproliferative Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplasms, Plasma Cell
- Myelodysplastic-Myeloproliferative Diseases
- Lymphoma
- Myelodysplastic Syndromes
- Primary Myelofibrosis
- Multiple Myeloma
- Leukemia
- Leukemia, Myeloid
- Lymphoma, Non-Hodgkin
- Leukemia, Myelomonocytic, Chronic
- Leukemia, Myelomonocytic, Juvenile
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Anti-Bacterial Agents
- Adjuvants, Immunologic
- Antibiotics, Antineoplastic
- Antifungal Agents
- Antitubercular Agents
- Antibiotics, Antitubercular
- Cyclophosphamide
- Lenograstim
- Fludarabine
- Mycophenolic Acid
- Sirolimus
- Busulfan
Other Study ID Numbers
- MCC-18766
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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.
Clinical Trials on Myelodysplastic Syndromes
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedPreviously Treated Myelodysplastic Syndromes | Secondary Myelodysplastic Syndromes | de Novo Myelodysplastic SyndromesUnited States
-
National Cancer Institute (NCI)CompletedPreviously Treated Myelodysplastic Syndromes | Secondary Myelodysplastic Syndromes | de Novo Myelodysplastic SyndromesUnited States
-
GCP-Service International West GmbHSaint-Louis Hospital, Paris, France; University of Florence; Medical University... and other collaboratorsNot yet recruitingLow Risk Myelodysplastic SyndromesSpain, Poland, Italy, Germany, France
-
Dana-Farber Cancer InstituteCompletedMyelodysplastic Syndromes (MDS)United States
-
TJ Biopharma Co., Ltd.Recruiting
-
National Heart, Lung, and Blood Institute (NHLBI)National Cancer Institute (NCI)RecruitingMyelodysplastic Syndromes (MDS)United States, Israel
-
AbbVieCelgene; Genentech, Inc.CompletedMyelodysplastic Syndromes (MDS)United States, Australia, Germany
-
AbbVieGenentech, Inc.Active, not recruitingMyelodysplastic Syndromes (MDS)United States, Australia, Canada, France, Germany, Italy, United Kingdom
-
The First Affiliated Hospital with Nanjing Medical...UnknownMyelodysplastic Syndromes (MDS)China
-
Sumitomo Pharma America, Inc.TerminatedMyelodysplastic Syndromes (MDS)United States
Clinical Trials on Fludarabine
-
National Institute of Arthritis and Musculoskeletal...CompletedPsoriasis | Arthritis, PsoriaticUnited States
-
Nantes University HospitalCyceronNot yet recruiting
-
Emory UniversityCompletedSickle Cell Disease | Bone Marrow TransplantationUnited States
-
Naoyuki G. Saito, M.D., Ph.D.WithdrawnAcute Myeloid Leukemia | Myelodysplastic Syndromes | Chronic Myeloid Leukemia | Acute Lymphocytic LeukemiaUnited States
-
National Institute of Arthritis and Musculoskeletal...CompletedSystemic Lupus Erythematosus | Glomerulonephritis | Lupus NephritisUnited States
-
University Hospital, CaenCNRS, UMR ISTCT 6301, LDM-TEP Groupe, GIP Cyceron, Caen, FranceCompletedUntreated B-Chronic Lymphocytic Leukemia or Diffuse Large B Cells Lymphoma PatientsFrance
-
University of Illinois at ChicagoCompletedAcute Myeloid Leukemia | Polycythemia Vera | Multiple Myeloma | Myelofibrosis | Acute Leukemia | Chronic Myelogenous Leukemia | Aplastic Anemia | Myeloproliferative Disorder | Hodgkin's Disease | Malignant Lymphoma | Lymphocytic LeukemiaUnited States
-
Massachusetts General HospitalTerminatedMultiple Myeloma | Hodgkin Disease | Non Hodgkin's LymphomaUnited States
-
Zhujiang HospitalFirst Affiliated Hospital, Sun Yat-Sen University; Nanfang Hospital of Southern... and other collaboratorsUnknownLeukemia Relapse | Chronic Graft-versus-host-disease
-
German CLL Study GroupCompletedAnemia | Chronic Lymphocytic LeukemiaGermany