Working… Menu
Trial record 95 of 126 for:    "Acute Leukemia" | "Antimetabolites, Antineoplastic"

Calcineurin Inhibitor-Free GVHD Prevention Regimen After Related Haplo PBSCT

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03018223
Recruitment Status : Active, not recruiting
First Posted : January 11, 2017
Last Update Posted : July 8, 2019
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

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.

Condition or disease Intervention/treatment Phase
Non-Hodgkin's Lymphoma Acute Leukemia in Remission Chronic Myeloid Leukemia Primary Myelofibrosis Chronic Myelomonocytic Leukemia Myelodysplastic Syndromes Hodgkin Lymphoma Multiple Myeloma 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) Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Calcineurin Inhibitor-Free GVHD Prevention Regimen After Related Haploidentical Peripheral Blood Stem Cell Transplantation
Actual Study Start Date : January 10, 2017
Actual Primary Completion Date : November 2018
Estimated Study Completion Date : January 2021

Arm Intervention/treatment
Experimental: Conditioning/HCT/GVHD Prophylaxis

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
Drug: Fludarabine
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 Name: Fludara, Oforta

Drug: Busulfan
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 Name: Busulfex, Myleran

Drug: Cyclophosphamide
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 Name: Cytoxan

Radiation: Total body irradiation (TBI)
Reduced intensity conditioning: 200 centigray (cGy) on day -1.
Other Name: radiotherapy

Procedure: Peripheral Blood Hematopoietic Cell Transplantation (HCT)
On day 0, patients will receive a peripheral blood hematopoietic cell graft.
Other Name: cell graft

Drug: Sirolimus (SIR)
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 Name: Rapamune

Drug: Mycophenolate mofetil (MMF)
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 Name: CellCept

Drug: Granulocyte-colony stimulating factor (G-CSF)
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 Name: Neupogen, Filgrastim

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Incidence of Chronic GVHD [ Time Frame: 1 year post HCT ]
    Cumulative incidence and severity of chronic GVHD by 1 year. Chronic GVHD diagnosis and severity scoring will follow National Institutes of Health (NIH) Consensus guidelines.

  2. Overall Survival (OS) [ Time Frame: Up to 1 year post HCT ]
    Overall survival defined as time from transplant to death or last follow-up.

  3. Progression Free Survival (PFS) [ Time Frame: Up to 1 year post HCT ]
    Progression-free survival defined as the minimum time interval from transplant to relapse/recurrence, to death or to last follow-up.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03018223

Layout table for location information
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Layout table for investigator information
Principal Investigator: Nelli Bejanyan, M.D. H. Lee Moffitt Cancer Center and Research Institute

Additional Information:
Layout table for additonal information
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute Identifier: NCT03018223     History of Changes
Other Study ID Numbers: MCC-18766
First Posted: January 11, 2017    Key Record Dates
Last Update Posted: July 8, 2019
Last Verified: July 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Acute leukemia in CR
Chronic myeloid leukemia
Non-Hodgkin lymphoma in high risk
Graft vs. Host Disease
Hematopoietic cell transplant (HCT)
Additional relevant MeSH terms:
Layout table for MeSH terms
Antimetabolites, Antineoplastic
Multiple Myeloma
Lymphoma, Non-Hodgkin
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Primary Myelofibrosis
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Myeloid
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Mycophenolic Acid