Adoptive Immunotherapy in Relapsed Hematological Malignancy: Early GVHD Prophylaxis

NCT02593123 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MCC-14-10739HM20005586
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

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)

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 2 years following stem cell transplant

Secondary Outcomes (9)

• 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.

  60 Days Following Stem Cell Transplant

• The Probability of Overall Survival (OS) Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort)

  Randomization up to 2 years

• Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) With Acute Graft Vs Host Disease (GVHD)

  60 Days following stem cell transplant

• Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) Diagnosed With Chronic Graft vs Host Disease (GVHD)

  60 Days following stem cell transplant

• Differences Between Patients Randomized to MMF-30 (Control Cohort) and MMF-15 (Investigational Cohort) Diagnosed With Opportunistic Infections

  60 Days following stem cell transplant

Study Arms (2)

Arm I (MMF-15, sargramostim)

EXPERIMENTAL

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.

Drug: mycophenolate mofetil; Biological: Sargramostim

Arm II (MMF-30, filgrastim)

ACTIVE COMPARATOR

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.

Drug: mycophenolate mofetil; Biological: Filgrastim

Interventions

mycophenolate mofetil DRUG

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

Also known as: CellCept

Arm I (MMF-15, sargramostim); Arm II (MMF-30, filgrastim)

Sargramostim 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.

Also known as: GM-CSF, colony stimulating factor 2, CSF2, granulocyte macrophage colony stimulating factor

Arm I (MMF-15, sargramostim)

Filgrastim 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.

Also known as: G-CSF, GCSF, colony-stimulating factor 3, CSF 3, granulocyte colony stimulating factor

Arm II (MMF-30, filgrastim)

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• Massey Cancer Center: collaborator

Study Sites (1)

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Hodgkin Disease; Leukemia, Lymphoid; Lymphoma; Leukemia; Neoplasms, Plasma Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Mycophenolic Acid; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; Colony-Stimulating Factors; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. Amir Toor, Principal Investigator
• Organization: Virginia Commonwealth University Massey Cancer Center

amir.toor@vcuhealth.org

804 828 5116

Study Officials

• Amir A Toor, MD

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2015
• First Posted: October 30, 2015
• Study Start: November 4, 2015
• Primary Completion: March 18, 2022
• Study Completion: March 18, 2022
• Last Updated: January 23, 2023
• Results First Posted: January 23, 2023

Record last verified: 2023-01

Locations

US (1)