Clinical trial NCT04473911: Haplo Peripheral Blood Sct In GVHD Prevention
Official title: Reduced Intensity Haploidentical Peripheral Blood Stem Cell Transplantation With Post-transplant Cyclophosphamide and Sirolimus/Mycophenolate Mofetil/RGI-2001 Based GVHD Prevention: a Pilot Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: GVHD
AML
ALL
MDS
MPN
CMML
Hodgkin Lymphoma
Non Hodgkin Lymphoma
Blood Stem Cell Transplant Failure
Graft Vs Host Disease
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndromes
Myeloproliferative Disorder
Chronic Myelomonocytic Leukemia
Chemosensitive Hodgkin Lymphoma
Keywords: GVHD
AML
ALL
MDS
MPN
CMML
Hodgkin Lymphoma
Non Hodgkin Lymphoma
Blood Stem Cell Transplant Failure
Graft Vs Host Disease
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndromes
Myeloproliferative Disorder
Chronic Myelomonocytic Leukemia
Chemosensitive Hodgkin Lymphoma
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Regimmune Corporation
First posted: 2020-07-16
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This research study is studying the RGI-2001 for preventing Graft-vs-Host Disease (GVHD) in people with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), myeloproliferative disorders (MPN), chronic myelomonocytic leukemic (CMML), chemosensitive hodgkin lymphoma (HL), or Non-Hodgkin lymphoma (NHL).who will have a blood stem cell transplantation.

* GVHD is a condition in which cells from the donor's tissue attack the organs.
* RGI-2001 is an investigational treatment

Detailed description: * This is a pilot study in subjects undergoing reduced-intensity haploidentical peripheral blood stem cell transplantation who will receive graft-versus-host disease prevention with post-transplant cyclophosphamide, followed by sirolimus, mycophenolate mofetil, and RGI-2001.
* The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
* The standard of care drugs of fludarabine, cyclophosphamide, melphalan, radiation, sirolimus, and mycophenolate mofetil are all FDA approved.

  * Eligible Participants will be placed in 1 of 2 groups, per physicians discretion:
  * Regimen #1 :

    * Before stem cell transplant:Fludarabine + Cyclophosphamide + Radiation
    * After stem cell transplant: Cyclophosphamide + Sirolimus +Mycophenolate mofetil + RGI-2001
  * Regimen #2

    * Before stem cell transplant: fludarabine + melphalan + radiation
    * After stem cell transplant: cyclophosphamide + sirolimus +Mycophenolate mofetil + RGI-2001
* A total of 20 participants will be enrolled to this trial
* The U.S. Food and Drug Administration (FDA) has not approved RGI-2001 as a treatment for any disease.

Eligibility criteria: Inclusion Criteria:

* Men or women ≥ 18 and ≤ 80 years old
* Diagnosis of hematological malignancy:

  * Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in morphologic complete remission
  * Myelodysplastic syndrome (MDS), myeloproliferative disorders (MPN), or chronic myelomonocytic leukemic (CMML) with \< 5% blasts in blood or bone marrow
  * Chemosensitive Hodgkin lymphoma (HL) or Non-Hodgkin lymphoma (NHL)
* Patients must be undergoing haploidentical allogeneic hematopoietic cell transplantation, defined as 1st or 2nd degree relative with at least 5/10 matching at HLA-A, -B, -C, DR, and DQ.
* ECOG performance status ≤2
* Patients with adequate physical function as measured by:

  * Cardiac: Left ventricular ejection fraction at rest must be ≥ 40%, or shortening fraction \>25%
  * Hepatic:

    * Bilirubin ≤ 2.5 mg/dL, except for patients with Gilbert's syndrome or hemolysis
    * ALT, AST, and Alkaline Phosphatase \< 5 x ULN
  * Renal: Serum creatinine within normal range, or if serum creatinine is outside normal range, then renal function (measured or estimated creatinine clearance or GFR) ≥ 40mL/min/1.73m2
  * Pulmonary: DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Prior allogeneic hematopoietic stem cell transplantation. (Patients may have received a prior autologous hematopoietic stem cell transplant.)
* Participants who are receiving any other investigational agents within 14 days prior to RGI-2001 dosing. Thus, participants must stop investigational agents by Day -9 prior to transplant.
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, recent myocardial infarction or stroke, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients with active or uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
* Planned use of prophylactic donor lymphocyte infusion (DLI) therapy.
* Pregnant and breast-feeding women are ineligible because they are not eligible for hematopoietic stem cell transplantation.
* HIV-positive participants and patients with active Hepatitis B or C are ineligible

Primary outcomes:
measure: Number of patients achieving successful donor engraftment
timeFrame: 60 Days
Secondary outcomes:
measure: 100-day non-relapse mortality (NRM) rate.
timeFrame: 100 Days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Zachariah DeFilipp, MD
role: PRINCIPAL_INVESTIGATOR
References: