Study of PRO 140 for Prophylaxis of Acute GVHD in Patients Undergoing RIC Allogenic Stem-Cell Transplantaton

• Status: Unknown status
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is an Open-Label, Single-Arm, Phase II Multicenter Study of the Safety and Efficacy of PRO 140 for Prophylaxis of Acute Graft-Versus-Host Disease (GVHD) in Patients Undergoing Reduced Intensity Conditioning (RIC) Allogeneic Stem-Cell Transplantation.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: CytoDyn, Inc.
• Collaborator: Amarex Clinical Research
• Treatments: HIV Antibodies; Leronlimab; PRO-140 monoclonal antibody

Criteria

Inclusion Criteria

Subjects may be included in the study only if they meet all of the following inclusion criteria:

1. Patients ≥18 years of age with a hematologic malignancy other than aplastic anemia or primary myelofibrosis, scheduled to undergo RIC allogeneic SCT with a peripheral blood stem cell graft, using Fludarabine/Busulfan (Flu/Bu) conditioning and Tacrolimus/ Methotrexate (Tac/MTX) GVHD prophylaxis. The following diagnoses are included:

• Acute leukemia - Acute myelogenous leukemia (AML), Acute lymphoblastic leukemia (ALL) or acute bi-phenotypic leukemia.

Note: Patients should have documentation of complete remission within 6 weeks prior to their transplant. Complete remission is defined as <5% blasts on a bone marrow biopsy and absence of any known extramedullary disease.

• Chronic myelogenous leukemia (CML) in any stage, but with documentation of <5% blasts on a bone marrow biopsy within 6 weeks prior to transplant.

• Myelodysplastic syndrome (MDS) of any subtype, but with documentation of <5% blasts on a bone marrow biopsy within 6 weeks prior to transplant.

• Myeloproliferative disorders other than primary myelofibrosis.

• Lymphoma - All types of lymphoma are eligible.

• Chronic lymphocytic leukemia (CLL) and Prolymphocytic leukaemia (PLL).

2. Patients who meet institutional eligibility criteria for allogeneic SCT:

• Renal function: Serum creatinine ≤ 2.

• Hepatic function: Baseline direct bilirubin, ALT or AST lower than three times the upper limit of normal.

• Pulmonary: FVC or FEV1 ≥ 40% predicted.

• Cardiac ejection fraction ≥ 40%.

• Clinically normal resting 12-lead ECG at screening visit or, if abnormal, considered not clinically significant by the PI Note: Prior documented echocardiogram and pulmonary function tests within the last 3 months of the Screening Visit is acceptable. If these are not performed within last 3 months, then these tests must be completed within the Screening Phase. In case the test is repeated between the Screening Visit and the First Treatment Visit, the most recent results will be used for the eligibility assessment.

3. HLA matched sibling or URD at least 7/8 HLA-A, -B, -C and -DRB1 matching by high-resolution molecular typing and will meet eligibility criteria to serve as a peripheral blood stem-cell donor.

4. Karnofsky scores ≥ 70% at the time of screening.

5. Capacity to understand and sign the study informed consent form.

6. Negative pregnancy test. Women of childbearing potential (not having had a hysterectomy, a bilateral oophorectomy or bilateral tubal ligation, or be post-menopausal with a total cessation of menses of > 1 year) must agree to use documented reliable method(s) of contraception. Men should agree to use condoms during the study period.

7. Co-enrollment in other clinical trials that do not include experimental GVHD therapies is allowed.

Inclusion Criteria

Subjects may be included in the study only if they meet all of the following inclusion criteria:

1. Patients ≥18 years of age with a hematologic malignancy other than aplastic anemia or primary myelofibrosis, scheduled to undergo RIC allogeneic SCT with a peripheral blood stem cell graft, using Fludarabine/Busulfan (Flu/Bu) conditioning and Tacrolimus/ Methotrexate (Tac/MTX) GVHD prophylaxis. The following diagnoses are included:

• Acute leukemia - Acute myelogenous leukemia (AML), Acute lymphoblastic leukemia (ALL) or acute bi-phenotypic leukemia.

Note: Patients should have documentation of complete remission within 6 weeks prior to their transplant. Complete remission is defined as <5% blasts on a bone marrow biopsy and absence of any known extramedullary disease.

• Chronic myelogenous leukemia (CML) in any stage, but with documentation of <5% blasts on a bone marrow biopsy within 6 weeks prior to transplant.

• Myelodysplastic syndrome (MDS) of any subtype, but with documentation of <5% blasts on a bone marrow biopsy within 6 weeks prior to transplant.

• Myeloproliferative disorders other than primary myelofibrosis.

• Lymphoma - All types of lymphoma are eligible.

• Chronic lymphocytic leukemia (CLL) and Prolymphocytic leukaemia (PLL).

2. Patients who meet institutional eligibility criteria for allogeneic SCT:

• Renal function: Serum creatinine ≤ 2.

• Hepatic function: Baseline direct bilirubin, ALT or AST lower than three times the upper limit of normal.

• Pulmonary: FVC or FEV1 ≥ 40% predicted.

• Cardiac ejection fraction ≥ 40%.

• Clinically normal resting 12-lead ECG at screening visit or, if abnormal, considered not clinically significant by the PI Note: Prior documented echocardiogram and pulmonary function tests within the last 3 months of the Screening Visit is acceptable. If these are not performed within last 3 months, then these tests must be completed within the Screening Phase. In case the test is repeated between the Screening Visit and the First Treatment Visit, the most recent results will be used for the eligibility assessment.

3. HLA matched sibling or URD at least 7/8 HLA-A, -B, -C and -DRB1 matching by high-resolution molecular typing and will meet eligibility criteria to serve as a peripheral blood stem-cell donor.

4. Karnofsky scores ≥ 70% at the time of screening.

5. Capacity to understand and sign the study informed consent form.

6. Negative pregnancy test. Women of childbearing potential (not having had a hysterectomy, a bilateral oophorectomy or bilateral tubal ligation, or be post-menopausal with a total cessation of menses of > 1 year) must agree to use documented reliable method(s) of contraception. Men should agree to use condoms during the study period.

7. Co-enrollment in other clinical trials that do not include experimental GVHD therapies is allowed.

Exclusion Criteria

Subjects will be excluded from the study if they meet one or more of the following exclusion criteria:

1. Patients with aplastic anemia or primary myelofibrosis. Patients with marrow fibrosis secondary to MDS, AML or a myeloproliferative disorder other than primary myelofibrosis are eligible.

2. Patients who are not expected to be available for follow-up in our institution for at least 180 days after the transplant.

3. Prior allogeneic SCT.

4. Uncontrolled bacterial, viral or fungal infections.

5. Prior use of any experimental or approved CCR5 modulators including maraviroc and PRO 140

6. Patients receiving other investigational drugs for GVHD.

7. Patients with prior malignancies are excluded unless treated with curative intent and known to be free of disease for at least 2 years.

8. Presence of fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated

9. Patients who are HIV positive

10. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study

11. Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy