NCT02506231

Brief Summary

The purpose of this study is to assess the impact of folinic acid (FA) -rescue following methotrexate (MTX) graft-versus-host disease (GVHD) prophylaxis on regimen related toxicity and transplantation outcomes after allogeneic hematopoietic cell transplantation (alloHCT) in a double blind randomized controlled trial.

Trial Health

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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
160

participants targeted

Target at P75+ for phase_2

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 13, 2015

Completed
10 days until next milestone

First Posted

Study publicly available on registry

July 23, 2015

Completed
2 months until next milestone

Study Start

First participant enrolled

October 1, 2015

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2017

Completed
Last Updated

July 24, 2015

Status Verified

June 1, 2015

Enrollment Period

2 years

First QC Date

July 13, 2015

Last Update Submit

July 23, 2015

Conditions

Graft vs Host DiseaseAllogeneic Hematopoietic Cell TransplantationMucositis

Keywords

Allogeneic hematopoietic cell transplantationGVHD prophylaxisMethotrexateFolinic acidLeucovorinMucositis

Outcome Measures

Primary Outcomes (2)

  • Incidence of severe (grade 3-4) oral mucositis according to the WHO scale

    According to the WHO (world health organization) oral mucositis grading scale

    30 days

  • Duration (in days) of severe (grade 3-4) oral mucositis according to the WHO scale

    According to the WHO (world health organization) oral mucositis grading scale

    30 days

Secondary Outcomes (24)

  • Incidence of oral mucositis

    30 days

  • Grade of oral mucositis

    30 days

  • Time to neutrophil recovery

    30 days

  • Time to platelet recovery

    60 days

  • Adherence to methotrexate schedule

    14 days

  • +19 more secondary outcomes

Study Arms (2)

Folinic acid

EXPERIMENTAL

Patients will be randomly assigned by central randomization in a 1:1 ratio to receive folinic acid (FA) or placebo starting 24h after each MTX dose for 24h. Oral FA 15 mg/dose or placebo will be given every 8h after MTX administration on day 1 (3 doses), and every 6h (4 doses) on days 3 and 6.

Drug: Folinic acid

Placebo

PLACEBO COMPARATOR

Patients will be randomly assigned by central randomization in a 1:1 ratio to receive folinic acid (FA) or placebo starting 24h after each MTX dose for 24h. Oral FA 15 mg/dose or placebo will be given every 8h after MTX administration on day 1 (3 doses), and every 6h (4 doses) on days 3 and 6.

Drug: Placebo

Interventions

Folinic acidDRUG
Also known as: leucovorin
Folinic acid
PlaceboDRUG
Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Acute leukemia in complete remission (CR) or myelodysplastic syndrome;
  • First transplantation;
  • Peripheral blood graft;
  • Matched sibling or unrelated donor or one antigen or allelic mismatched sibling or unrelated donor (10/10 or 9/10 human leukocyte antigen match );
  • Myeloablative or reduced intensity preparative regimen;
  • Post-transplant GVHD prophylaxis consisting of a calcineurin inhibitor (CSA or tacrolimus) and methotrexate;
  • Glutamate Pyruvate Transaminase (GPT) \< 3 times upper normal limit (UNL) and creatinine ≤ 1.4 mg%;
  • Written informed consent;

You may not qualify if:

  • True non-myeloablative preparative regimen (TBI 200 +/- fludarabine);
  • Acute leukemia not in remission;
  • GPT \> 3 times upper normal limit or creatinine \> 1.4 mg%;
  • Bone marrow, haploidentical or cord blood grafts;

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • Yeshurun M, Rozovski U, Pasvolsky O, Wolach O, Ram R, Amit O, Zuckerman T, Pek A, Rubinstein M, Sela-Navon M, Raanani P, Shargian-Alon L. Efficacy of folinic acid rescue following MTX GVHD prophylaxis: results of a double-blind, randomized, controlled study. Blood Adv. 2020 Aug 25;4(16):3822-3828. doi: 10.1182/bloodadvances.2020002039.

    PMID: 32790844DERIVED

MeSH Terms

Conditions

Graft vs Host DiseaseMucositis

Interventions

Leucovorin

Condition Hierarchy (Ancestors)

Immune System DiseasesGastroenteritisGastrointestinal DiseasesDigestive System DiseasesMouth DiseasesStomatognathic Diseases

Intervention Hierarchy (Ancestors)

FormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsCoenzymesEnzymes and Coenzymes

Study Officials

  • Moshe Yeshurun, MD

    Rabin Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Moshe Yeshurun, MD

CONTACT

972-50-4065543moshey@clalit.org.il

Liat Shargian, MD

CONTACT

972-54-2394930LIATSHR@clalit.org.il

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 13, 2015

First Posted

July 23, 2015

Study Start

October 1, 2015

Primary Completion

October 1, 2017

Last Updated

July 24, 2015

Record last verified: 2015-06