Clinical trial NCT02593123: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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)
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: Massey Cancer Center
First posted: 2015-10-30
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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).
timeFrame: Up to 2 years following stem cell transplant
Secondary outcomes:
measure: 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.
timeFrame: 60 Days Following Stem Cell Transplant
measure: The Probability of Overall Survival (OS) Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort)
timeFrame: Randomization up to 2 years
measure: Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) With Acute Graft Vs Host Disease (GVHD)
timeFrame: 60 Days following stem cell transplant
measure: Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) Diagnosed With Chronic Graft vs Host Disease (GVHD)
timeFrame: 60 Days following stem cell transplant
measure: Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) Diagnosed With Opportunistic Infections
timeFrame: 60 Days following stem cell transplant
measure: Determine the Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) With Diagnosis of Engraftment Loss.
timeFrame: 60 Days Following Stem Cell Transplant
measure: Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort)Diagnosed With Differences in the Rates of Engraftment Syndrome.
timeFrame: 60 Days Following Stem Cell Transplant
measure: 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).
timeFrame: 100 Days following Stem Cell Transplant
measure: 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).
timeFrame: 100 Days Following Stem Cell Transplantation
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
Study officials:
affiliation: Massey Cancer Center
name: Amir A Toor, MD
role: PRINCIPAL_INVESTIGATOR
References: