NCT03018223 · REGISTRY CONDITION SEARCH

Calcineurin Inhibitor-Free GVHD Prevention Regimen After Related Haplo PBSCT

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: COMPLETED
Registry last update: 2021-09-16

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Incidence of Grade II-IV Acute Graft vs. Host Disease (GVHD)

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outcome · POSTED

Incidence of Chronic GVHD

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Progression Free Survival (PFS)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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.
healthy Volunteers: true
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Pre-HCT Conditioning, HCT, GVHD Prophylaxis. 1. Conditioning regimen: To reduce heterogeneity, two commonly used myeloablative (MAC) and reduced intensity (RIC) regimens are permitted on this trial. Myeloablative conditioning: fludarabine, busulfan. Reduced intensity conditioning: fludarabine, cyclophosphamide, total body irradiation. 2. Peripheral blood hematopoietic cell transplantation 3. Graft vs. Host Disease (GVHD) prevention treatment: cyclophosphamide, mycophenolate mofetil, sirolimus. 4. Growth factor support: G-CSF
intervention Names
Drug: Fludarabine
Drug: Busulfan
Drug: Cyclophosphamide
Radiation: Total body irradiation (TBI)
Procedure: Peripheral Blood Hematopoietic Cell Transplantation (HCT)
Drug: Sirolimus (SIR)
Drug: Mycophenolate mofetil (MMF)
Drug: Granulocyte-colony stimulating factor (G-CSF)
label
Conditioning/HCT/GVHD Prophylaxis
type
EXPERIMENTAL

interventions

arm Group Labels
Conditioning/HCT/GVHD Prophylaxis
description
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.
name
Fludarabine
other Names
Fludara, Oforta
type
DRUG
arm Group Labels
Conditioning/HCT/GVHD Prophylaxis
description
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).
name
Busulfan
other Names
Busulfex, Myleran
type
DRUG
arm Group Labels
Conditioning/HCT/GVHD Prophylaxis
description
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.
name
Cyclophosphamide
other Names
Cytoxan
type
DRUG
arm Group Labels
Conditioning/HCT/GVHD Prophylaxis
description
Reduced intensity conditioning: 200 centigray (cGy) on day -1.
name
Total body irradiation (TBI)
other Names
radiotherapy
type
RADIATION
arm Group Labels
Conditioning/HCT/GVHD Prophylaxis
description
On day 0, patients will receive a peripheral blood hematopoietic cell graft.
name
Peripheral Blood Hematopoietic Cell Transplantation (HCT)
other Names
cell graft
type
PROCEDURE
arm Group Labels
Conditioning/HCT/GVHD Prophylaxis
description
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.
name
Sirolimus (SIR)
other Names
Rapamune
type
DRUG
arm Group Labels
Conditioning/HCT/GVHD Prophylaxis
description
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.
name
Mycophenolate mofetil (MMF)
other Names
CellCept
type
DRUG
arm Group Labels
Conditioning/HCT/GVHD Prophylaxis
description
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.
name
Granulocyte-colony stimulating factor (G-CSF)
other Names
Neupogen, Filgrastim
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

PREVENTION

Enrollment

count: 32
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Incidence of Grade II-IV Acute Graft vs. Host Disease (GVHD)
time Frame
100 days post hematopoietic cell transplant (HCT)

secondary Outcomes

description
Cumulative incidence of chronic GVHD by 1 year. Chronic GVHD diagnosis follow National Institutes of Health (NIH) Consensus guidelines.
measure
Incidence of Chronic GVHD
time Frame
1 year post HCT
description
Overall survival is defined as time from transplant to death or last follow-up, and is reported as percentage of surviving participants.
measure
Overall Survival (OS)
time Frame
Up to 1 year post HCT
description
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.
measure
Progression Free Survival (PFS)
time Frame
Up to 1 year post HCT

Full study description

brief Summary: 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.

Source references

references

citation
Bejanyan N, Pidala JA, Wang X, Thapa R, Nishihori T, Elmariah H, Lazaryan A, Khimani F, Davila ML, Mishra A, Faramand R, Jain MD, Ochoa L, Perez LE, Liu H, Alsina M, Kharfan-Dabaja MA, Fernandez H, Nieder ML, Locke FL, Anasetti C, Ayala E. A phase 2 trial of GVHD prophylaxis with PTCy, sirolimus, and MMF after peripheral blood haploidentical transplantation. Blood Adv. 2021 Mar 9;5(5):1154-1163. doi: 10.1182/bloodadvances.2020003779.
pmid
33635333
type
DERIVED