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Adoptive Immunotherapy in Relapsed Hematological Malignancy: Early GVHD Prophylaxis

Primary Purpose

Hodgkin's Lymphoma, Lymphoid Leukemia, Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
mycophenolate mofetil
Sargramostim
Filgrastim
Sponsored by
Virginia Commonwealth University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hodgkin's Lymphoma focused on measuring Donor Type (Matched Related Donor or Matched Unrelated Donor)

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Virginia Commonwealth University/Massey Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (MMF-15, sargramostim)

Arm II (MMF-30, filgrastim)

Arm Description

Patients receive mycophenolate mofetil (MMF) PO or IV twice daily (BID) on days 0-15 and sargramostim SC from post-transplant day 4 until neutrophil engraftment.

Patients receive mycophenolate mofetil PO or IV (twice daily) BID on days 0-30 and filgrastim G-CSF from post-transplant day 4 until neutrophil engraftment.

Outcomes

Primary Outcome Measures

The Number of Patients With Relapse-free/Donor Lymphocyte Infusion(DLI)-Free Survival Rates Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort).
The primary outcome in this study is event-free survival, where the conditional events are the occurrence of relapse DLI.

Secondary Outcome Measures

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 10E3per microL Counts.
Day 60 donor-derived (dd) cluster of differentiation (CD)3 counts measured by 10E3per microL.
The Probability of Overall Survival (OS) Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort)
Overall survival (days to event or survival: time-to-event; survival: categorical)
Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) With Acute Graft Vs Host Disease (GVHD)
The number of patients diagnosed with acute acute GVHD between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort)
Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) Diagnosed With Chronic Graft vs Host Disease (GVHD)
The differences in the rates of chronic GVHD between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort)
Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) Diagnosed With Opportunistic Infections
The number of patients diagnosed with an opportunistic infections.
Determine the Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) With Diagnosis of Engraftment Loss.
Number of patients with engraftment loss.
Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort)Diagnosed With Differences in the Rates of Engraftment Syndrome.
Number of patients diagnosed with engraftment syndrome.
Differences in the Rates of Achieving Donor Chimerisms (the Percentage of DNA in the Sample Which Comes From the Donor) Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort).
Number of patients that achieved donor chimerisms by day 100.
Differences in the Rates of T-cell Recovery Kinetics Following Stem Cell Transplantation (SCT) Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort).
Number of T Cells 10E3 per microL per arm indicating rates of T-cell recovery by Day 100 following SCT.

Full Information

First Posted
October 29, 2015
Last Updated
January 4, 2023
Sponsor
Virginia Commonwealth University
Collaborators
Massey Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT02593123
Brief Title
Adoptive Immunotherapy in Relapsed Hematological Malignancy: Early GVHD Prophylaxis
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 Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
November 4, 2015 (Actual)
Primary Completion Date
March 18, 2022 (Actual)
Study Completion Date
March 18, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
Collaborators
Massey Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. 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 mycophenolate 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 human leukocyte antigen (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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin's Lymphoma, Lymphoid Leukemia, Lymphoma, Leukemia, Myeloma, Acute Lymphocytic Leukemia, Non Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Multiple Myeloma, Chronic Myelogenous Leukemia, Myelodysplastic Syndromes, Recurrent Acute Myeloid Leukemia, Adult, Recurrent Hodgkin Lymphoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Plasma Cell Myeloma, Recurrent Chronic Lymphocytic Leukemia, Recurrent Chronic Myelogenous Leukemia, Acute Myelogenous Leukemia
Keywords
Donor Type (Matched Related Donor or Matched Unrelated Donor)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (MMF-15, sargramostim)
Arm Type
Experimental
Arm Description
Patients receive mycophenolate mofetil (MMF) PO or IV twice daily (BID) on days 0-15 and sargramostim SC from post-transplant day 4 until neutrophil engraftment.
Arm Title
Arm II (MMF-30, filgrastim)
Arm Type
Active Comparator
Arm Description
Patients receive mycophenolate mofetil PO or IV (twice daily) BID on days 0-30 and filgrastim G-CSF from post-transplant day 4 until neutrophil engraftment.
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Other Intervention Name(s)
CellCept
Intervention Description
Given PO, by mouth, orally or IV, intravenous medication administration.
Intervention Type
Biological
Intervention Name(s)
Sargramostim
Other Intervention Name(s)
GM-CSF, colony stimulating factor 2, CSF2, granulocyte macrophage colony stimulating factor
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
G-CSF, GCSF, colony-stimulating factor 3, CSF 3, granulocyte colony stimulating factor
Intervention Description
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.
Primary Outcome Measure Information:
Title
The Number of Patients With Relapse-free/Donor Lymphocyte Infusion(DLI)-Free Survival Rates Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort).
Description
The primary outcome in this study is event-free survival, where the conditional events are the occurrence of relapse DLI.
Time Frame
Up to 2 years following stem cell transplant
Secondary Outcome Measure Information:
Title
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 10E3per microL Counts.
Description
Day 60 donor-derived (dd) cluster of differentiation (CD)3 counts measured by 10E3per microL.
Time Frame
60 Days Following Stem Cell Transplant
Title
The Probability of Overall Survival (OS) Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort)
Description
Overall survival (days to event or survival: time-to-event; survival: categorical)
Time Frame
Randomization up to 2 years
Title
Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) With Acute Graft Vs Host Disease (GVHD)
Description
The number of patients diagnosed with acute acute GVHD between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort)
Time Frame
60 Days following stem cell transplant
Title
Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) Diagnosed With Chronic Graft vs Host Disease (GVHD)
Description
The differences in the rates of chronic GVHD between patients randomized to MMF-30 (control cohort) and MMF-15 (investigational cohort)
Time Frame
60 Days following stem cell transplant
Title
Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) Diagnosed With Opportunistic Infections
Description
The number of patients diagnosed with an opportunistic infections.
Time Frame
60 Days following stem cell transplant
Title
Determine the Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) With Diagnosis of Engraftment Loss.
Description
Number of patients with engraftment loss.
Time Frame
60 Days Following Stem Cell Transplant
Title
Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort)Diagnosed With Differences in the Rates of Engraftment Syndrome.
Description
Number of patients diagnosed with engraftment syndrome.
Time Frame
60 Days Following Stem Cell Transplant
Title
Differences in the Rates of Achieving Donor Chimerisms (the Percentage of DNA in the Sample Which Comes From the Donor) Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort).
Description
Number of patients that achieved donor chimerisms by day 100.
Time Frame
100 Days following Stem Cell Transplant
Title
Differences in the Rates of T-cell Recovery Kinetics Following Stem Cell Transplantation (SCT) Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort).
Description
Number of T Cells 10E3 per microL per arm indicating rates of T-cell recovery by Day 100 following SCT.
Time Frame
100 Days Following Stem Cell Transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 Massey Cancer Center Virginia Commonwealth University 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amir A Toor, MD
Organizational Affiliation
Massey Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Commonwealth University/Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States

12. IPD Sharing Statement

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Adoptive Immunotherapy in Relapsed Hematological Malignancy: Early GVHD Prophylaxis

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