Haplo Peripheral Blood Sct In GVHD Prevention

Zachariah Michael DeFilipp

Status and phase: Completed; Phase 1

Conditions: Graft Vs Host Disease; CMML; Hodgkin Lymphoma; AML; Chemosensitive Hodgkin Lymphoma; Blood Stem Cell Transplant Failure; ALL; GVHD; Non Hodgkin Lymphoma; Myelodysplastic Syndromes; MPN; Myeloproliferative Disorder; MDS; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia

Treatments: Radiation: TBI; Drug: RGI-2001; Drug: Mycophenolate mofetil; Drug: FLUDARABINE; Drug: CYCLOPHOSPHAMIDE; Drug: Melphalan; Drug: Sirolimus

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04473911

19-336

Details and patient eligibility

About

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

Full 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.

Enrollment: 25 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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25 participants in 2 patient groups

Regimen 1: Fludarabine, Cyclophosphamide, and TBI

Experimental group

Description:

-. Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment. Two reduced intensity regimens will be allowed, according to the choice of the treating physician * Pre- stem cell transplant: * Fludarabine predetermined dose, intravenously, 4 times per cycle * Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion * Total body irradiation (TBI) once during treatment cycle * Post stem cell transplant: * Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion * Sirolimus: Predetermined dosage, predetermined number of time in cycle, oral. * 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

Treatment:

Drug: Sirolimus

Drug: CYCLOPHOSPHAMIDE

Drug: FLUDARABINE

Drug: Mycophenolate mofetil

Drug: RGI-2001

Drug: CYCLOPHOSPHAMIDE

Radiation: TBI

Regimen 2: Fludarabine, Melphalan, and TBI

Experimental group

Description:

-. Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment. Two reduced intensity regimens will be allowed, according to the choice of the treating physician * Pre- stem cell transplant: * Fludarabine predetermined dose, intravenously 3 times per cycle * Melphalan, infusion, determined dosage, once per cycle * Total body irradiation (TBI) once per cycle. * Post stem cell transplant * Cyclophosphamide predetermined dose, predetermined number of times in cycle, intravenous infusion * Sirolimus: Predetermined dosage, predetermined number of time in cycle, oral: * 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

Treatment:

Drug: Sirolimus

Drug: CYCLOPHOSPHAMIDE

Drug: Melphalan

Drug: FLUDARABINE

Drug: Mycophenolate mofetil

Drug: RGI-2001

Drug: CYCLOPHOSPHAMIDE

Radiation: TBI