Adoptive Immunotherapy in Relapsed Hematological Malignancy: Early GVHD Prophylaxis

NCT ID: NCT02593123

Last Updated: 2023-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-04
• Study Completion Date: 2022-03-18

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (MMF-15, sargramostim)

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.

Group Type: EXPERIMENTAL

mycophenolate mofetil

Intervention Type: DRUG

Given PO, by mouth, orally or IV, intravenous medication administration.

Sargramostim

Intervention Type: BIOLOGICAL

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.

Arm II (MMF-30, filgrastim)

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.

Group Type: ACTIVE_COMPARATOR

mycophenolate mofetil

Intervention Type: DRUG

Given PO, by mouth, orally or IV, intravenous medication administration.

Filgrastim

Intervention Type: BIOLOGICAL

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.

Interventions

mycophenolate mofetil

Given PO, by mouth, orally or IV, intravenous medication administration.

Intervention Type: DRUG

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Other Intervention Names

CellCept; GM-CSF; colony stimulating factor 2; CSF2; granulocyte macrophage colony stimulating factor; G-CSF; GCSF; colony-stimulating factor 3; CSF 3; granulocyte colony stimulating factor

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massey Cancer Center

OTHER

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amir A Toor, MD

Role: PRINCIPAL_INVESTIGATOR

Massey Cancer Center

Locations

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HM20005586

Identifier Type: OTHER

Identifier Source: secondary_id

MCC-14-10739

Identifier Type: -

Identifier Source: org_study_id