2018-0674 - IL-7 for T-Cell Recovery Post Haplo and CB Transplant - Phase I/II

Study Overview
=================
Brief Summary
-----------------
This phase I/II trial studies side effects and best dose of recombinant interleukin-7 in promoting immune cell recovery in patients with acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia, or myeloproliferative disease after a haploidentical or cord blood stem cell transplant. A haploidentical transplant is a transplant that uses stem cells from a donor that is partially (at least 50%) matched to the patient. Umbilical cord blood is a source of blood-forming cells that can be used for transplant, also known as a graft. However, there is a small number of blood-forming cells available in the transplant, which may delay the take of the graft in the recipient. Recombinant interleukin-7 may affect the take of the graft and the recovery of certain blood cells related to the immune system (called T-cells, natural killer cells, and B cells) in patients who have had a haploidentical or cord blood stem cell transplant.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To determine the safety and establish the optimal biologic dose of glycosylated recombinant human interleukin-7 (CYT107). SECONDARY OBJECTIVES: I. To determine the rate of cytomegalovirus (CMV), Epstein-Barr virus (EBV) and BK viral infections in umbilical cord blood stem cell transplantation (CBT) and haploidentical stem cell transplantation (haplo-SCT) patients who receive three doses of interleukin-7 (IL-7) following engraftment. II. To calculate the overall survival (OS), progression-free survival (PFS), and cumulative incidence of graft versus host disease (GVHD) and cumulative incidence of relapse. III. To evaluate the effects of CYT107 on the recovery of T, natural killer (NK) and B cell populations and their functions in vitro; these data will be used to identify the optimal dose to move to a phase II trial. OUTLINE: This is a dose-escalation study. Within 60-180 days after CBT, patients receive recombinant interleukin-7 intramuscularly (IM) or subcutaneously (SC) once per week for 3 weeks. After completion of study treatment, patients are followed for up to 3 years.

Official Title
-----------------
A Phase I/II Study of Recombinant Human Interleukin-7 to Promote T-Cell Recovery After Haploidentical and Cord Blood Stem Cell Transplantation

Conditions
-----------------
Acute Myeloid Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Cord Blood Transplant Recipient, Myelodysplastic Syndrome, Myeloproliferative Neoplasm

Intervention / Treatment
-----------------
* Biological: Recombinant Interleukin-7


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: English and non-English speaking patients are eligible. Patient post a cord blood transplant (CBT) or haplo-SCT, with matched unrelated donors (MUDs), both peripheral blood (PB) and marrow sources with documented absolute neutrophil engraftment Patients with documented engraftment but require granulocyte-colony stimulating factor (G-CSF) to treat myelosuppression induced by drugs used to treat or prevent infection are eligible Karnofsky performance status (KPS) > 60% Absence of dyspnea or hypoxia (< 90% of saturation by pulse oximetry on room air) Bilirubin =< 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN Prothrombin time (PT)/partial prothrombin time (PTT) < 1.5 x ULN Calculated creatinine clearance > 60 mL/min/1.73 m^2 Diagnosis of acute myeloid leukemia; myelodysplastic syndrome; chronic myeloid leukemia; myelofibrosis or myeloproliferative disease Exclusion Criteria: Pregnant or nursing History of lymphoid malignancy (including Hodgkin disease, non-Hodgkin lymphoma, acute lymphoblastic leukemia and chronic lymphocytic leukemia) or acute biphenotypic leukemia Patients with acute GVHD > grade 2 at any time during the post-transplant course Ongoing immunosuppressive therapy for the treatment of GVHD. Patients receiving GVHD prophylaxis will be allowed on this study History of Epstein-Barr virus (EBV) associated lymphoproliferation Active uncontrolled viral, bacterial or fungal infection History of autoimmune disease Receiving systemic corticosteroid therapy, budesonide is allowed Uncontrolled hypertension Corrected QT (QTc) prolongation (QTc > 470 ms) or prior history of significant arrhythmia or electrocardiogram (ECG) abnormalities Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements Patients with cognitive impairments and/or any past or current psychiatric illness that, in the opinion of the investigator, would interfere with adherence to study requirements or the ability and willingness to give written informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supportive care (recombinant interleukin-7)<br>Within 60-180 days after CBT, patients receive recombinant interleukin-7 IM or SC once per week for 3 weeks. | Biological: Recombinant Interleukin-7<br>* Given IM or SC<br>* Other names: Recombinant Human Interleukin-7;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities | Participants that had grade 3 or 4 graft versus host disease (GVHD), secondary graft failure, disease relapse, development of post-transplant lymphoproliferative disorder, development of progressive multifocal leukoencephalopathy or grade 3-4 organ failure attributable to recombinant human interleukin-7 (CYT107) and death. | Up to 42 days after first injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Number of participant that survived after 3 years. | Up to 3 years |