Allogeneic Stem Cell Transplantationin Relapsed Hematological Malignancy: Early GVHD Prophylaxis

Sponsor
Virginia Commonwealth University (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02593123
Collaborator
Massey Cancer Center (Other)
31
Enrollment
1
Location
2
Arms
121.9
Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Determine the relapse-free, donor lymphocyte infusion (DLI)-free survival in patients receiving the investigational regimen.This is a randomized phase II clinical trial, comparing two different dosing schedules of mycophyenolate mofetil for graft versus host disease (GVHD) prevention following allogeneic stem cell transplantation. Risk for relapse, GVHD and non-relapse mortality will be assessed. Adaptive randomization between two study arms will be performed based on T cell counts at day 60.

Detailed Description

In this study, the investigators will utilize a regimen combining low dose total body irradiation and rabbit ATG to facilitate stem cell transplantation (SCT) with HLA matched related and unrelated donors. Based on the hypothesis that early treatment interventions have significant late effects in allogeneic SCT, a simple intervention, varying the duration of intense immunosuppression following SCT, will be investigated in this study. This may allow more robust recovery of donor immune system cells in the first two months following transplantation and eventually result in lower risk of cancer relapse, while maintaining effective graft versus host disease (GVHD) control. Patients will be randomly assigned to receive GVHD prevention therapy using one of two different immunosuppressive regimens with tacrolimus & mycophenolate mofetil (MMF). Patients assigned to the investigational group will receive MMF for 15 days following SCT with growth factor support using granulocyte macrophage colony stimulating factor (GM-CSF) beginning on post-transplant day 4. Patients randomized to the standard treatment group will receive MMF for 30 days following SCT with cytokine support using granulocyte colony stimulating factor (G-CSF) beginning on post-transplant day 4. If one of these treatment groups demonstrates an improvement in donor immune cell recovery, there may be a slow increase in the likelihood of patients being assigned to that more successful treatment group. Eventually the two groups will be compared with respect to the likelihood of either relapse or GVHD developing.

Study Design

Study Type:
Interventional
Actual Enrollment :
31 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Adoptive Immunotherapy in Patients With Relapsed Hematological Malignancy: Effect of Duration and Intensity of Early GVHD Prophylaxis on Long-Term Clinical Outcomes
Study Start Date :
Nov 4, 2015
Anticipated Primary Completion Date :
Dec 31, 2025
Anticipated Study Completion Date :
Dec 31, 2025

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm I (MMF-15, sargramostim)

Patients receive mycophenolate mofetil PO or IV BID on days 1-15 and sargramostim SC from post-transplant day 4 until neutrophil engraftment.

Drug: mycophenolate mofetil
Given PO, by mouth, orally or IV, intravenous medication administration.
Other Names:
  • CellCept
  • Biological: Sargramostim
    GM-CSF beginning post-transplant day 4 and continuing until hematopoietic reconstitution. Patients in the MMF-15 cohort will receive sargramostim (GM-CSF) 250 mcg/m2/day beginning on post-transplant day 4 and continuing until neutrophil engraftment. Patients receiving GM-CSF will also receive inhaled corticosteroids, fluticasone (Flovent) 2 puffs twice daily, starting on post-transplant day 4 and stopping after cessation of GM-CSF, to diminish the risk of pneumonitis. Note: At investigator discretion, patients in the MMF-15 cohort who have preexisting pulmonary risk factors, will be permitted to receive G-CSF.
    Other Names:
  • GM-CSF
  • colony stimulating factor 2
  • CSF2
  • granulocyte macrophage colony stimulating factor
  • Experimental: Arm II (MMF-30, filgrastim)

    Patients receive mycophenolate mofetil PO or IV BID on days 1-30 and sargramostim SC from post-transplant day 4 until neutrophil engraftment.

    Drug: mycophenolate mofetil
    Given PO, by mouth, orally or IV, intravenous medication administration.
    Other Names:
  • CellCept
  • Biological: Filgrastim
    G-CSF beginning post-transplant day 4 and continuing until hematopoietic reconstitution. Patients in the MMF-30 cohort will receive filgrastim (G-CSF) 5 mcg/kg/day beginning on post-transplant day 4 and continuing until neutrophil engraftment.
    Other Names:
  • G-CSF
  • GCSF
  • colony-stimulating factor 3
  • CSF 3
  • granulocyte colony stimulating factor
  • Outcome Measures

    Primary Outcome Measures

    1. The differences in the relapse-free/donor lymphocyte infusion(DLI)-free survival rates between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort). [5 years]

      The primary outcome in this study is event-free survival, where the conditional events are the occurrence of relapse or DLI.

    Secondary Outcome Measures

    1. The difference between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort) day 60 donor-derived (dd) cluster of differentiation (CD)3. [5 years]

      Day 60 donor-derived (dd) cluster of differentiation (CD)3

    2. The differences in the Overall survival (OS) between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort) [5 years]

      Overall survival (days to event or survival: time-to-event; survival: categorical)

    3. The differences in the rates of acute GVHD between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort) [5 years]

      Acute GVHD (days to positive diagnosis: time-to-event; positive diagnosis: categorical)

    4. The differences in the rates of chronic GVHD between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort) [5 years]

      Chronic GVHD (days to positive diagnosis: time-to-event; positive diagnosis: categorical)

    5. The differences in the rates of opportunistic infections between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort) [5 years]

      Rate of opportunistic infection

    6. The differences in the rates of graft loss between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort) [5 years]

      Engraftment loss (days to loss: time-to-event; graft loss: categorical)

    7. The differences in the rates of engraftment syndrome between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort) [5 years]

      Engraftment syndrome (categorical)

    8. The differences in the rates of achieving donor chimerisms between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort). [5 years]

      DLI administration (days to administration: time-to-event; administration: categorical)

    9. The differences in the rates of T-cell recovery kinetics following SCT between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort). [5 years]

      Rates of T-cell recovery following SCT.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 74 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    • Any of the following high risk or recurrent hematological malignancies:

    • Hodgkin lymphoma (HL)

    • Non-Hodgkin lymphoma (NHL)

    • Chronic lymphocytic leukemia (CLL)

    • Multiple myeloma (MM)

    • Acute myelogenous leukemia (AML)

    • Acute lymphocytic leukemia (ALL)

    • Chronic myelogenous leukemia (CML)

    • Myelodysplastic syndrome (MDS)

    *Note: Determination that the malignancy is high risk will be made by the investigator.

    • Investigator determination that the patient is an appropriate candidate for reduced intensity allogeneic SCT with the standard Massey Cancer Center-Virginia Commonwealth Health System Bone Marrow Transplant MCC-VCUHS BMT Program regimen employed in this trial

    • Patients with or without previous myeloablative autologous transplant

    • HLA-matched stem cell donor, either related (6/6 or 5/6 loci matched) or unrelated (8/8 or 7/8 loci matched)

    *Note: Unrelated donors must be matched at HLA-A, -B, -C, and -DRB1 loci. However, a single locus mismatch will be acceptable in the event a more closely matched donor is not available.

    • Age ≥ 40 to < 75 years; patients 18 to 39 years of age will be eligible only if the investigator has determined that the patient has comorbidity(ies) precluding conventional allogeneic transplantation with full intensity myeloablative conditioning

    • Karnofsky Performance Status of 70-100%

    • Negative serology for HIV

    • Women who are not postmenopausal or have not undergone hysterectomy must have a documented negative serum pregnancy test per standard MCC-VCUHS BMT Program guidelines

    • Ability to understand and the willingness to sign a written informed consent document *Note: The consent form must be signed and dated prior to initiation of SCT preparative treatments.

    Exclusion Criteria

    • Previous therapeutic radiation therapy (RT) that exceeds critical structure tolerance doses as determined by a radiation oncologist

    • Uncontrolled viral, fungal, or bacterial infection

    • Active meningeal or central nervous system disease

    • Previous therapy with rabbit anti-thymocyte globulin (ATG); previous treatment with equine ATG is allowed if more than 3 months ago

    *Note: Previous myeloablative autologous transplant is permitted but not required.

    • Pregnancy or breastfeeding

    • Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Virginia Commonwealth University/Massey Cancer CenterRichmondVirginiaUnited States23298

    Sponsors and Collaborators

    • Virginia Commonwealth University
    • Massey Cancer Center

    Investigators

    • Principal Investigator: Amir A Toor, MD, Massey Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Virginia Commonwealth University
    ClinicalTrials.gov Identifier:
    NCT02593123
    Other Study ID Numbers:
    • MCC-14-10739
    • HM20005586
    First Posted:
    Oct 30, 2015
    Last Update Posted:
    Dec 22, 2021
    Last Verified:
    Dec 1, 2021

    Study Results

    No Results Posted as of Dec 22, 2021