Haplo Peripheral Blood Sct In GVHD Prevention

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04473911
• Other study ID #: 19-336
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 14, 2020
• Est. completion date: October 2024

Study information

• Verified date: March 2024
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Est. completion date: October 2024
• Est. primary completion date: October 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• ALL
• AML
• Blood Stem Cell Transplant Failure
• Chemosensitive Hodgkin Lymphoma
• Chronic Myelomonocytic Leukemia
• CMML
• Graft Vs Host Disease
• GVHD
• Hodgkin Disease
• Hodgkin Lymphoma
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Lymphoma
• Lymphoma, Non-Hodgkin
• MDS
• MPN
• Myelodysplastic Syndromes
• Myeloproliferative Disorder
• Myeloproliferative Disorders
• Non Hodgkin Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Drug:
• FLUDARABINE
predetermined dose, intravenously, a predetermined times per cycle Given in both pre stem cell and post stem cell cycles
• CYCLOPHOSPHAMIDE
?Cyclophosphamide predetermined dose, predetermined number of times in Given in pre-stem cell Regimen #1 Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion

Radiation:
• TBI
Total body irradiation (TBI) once per cycle.

Drug:
• Melphalan
Melphalan, infusion, determined dosage, once per cycle
• Sirolimus
Sirolimus: Predetermined dosage, predetermined number of time in cycle, oral: Please note that doses of sirolimus can be adjusted at the treating physician's discretion given the multiple drugs and other situations which affect its metabolism
• Mycophenolate mofetil
?Mycophenolate mofetil, oral or iv(predetermined dose or IV TID (based upon actual body weight), at predetermined times per cycle
• RGI-2001
IV, predetermined dose, weekly to 6 total doses
• CYCLOPHOSPHAMIDE
?Given in Post Stem Cell cycle of Regimen #1 and #2 Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Zachariah Michael DeFilipp	Regimmune Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients achieving successful donor engraftment	(absolute neutrophil count > 500/uL and = 90% donor cell chimerism)	60 Days
Secondary	100-day non-relapse mortality (NRM) rate.	The regimen will be considered as safe if 100d NRM rate is <=5%, and not safe if 100d NRM rate is =25%.	100 Days