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

Phase 1

Completed

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

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Supportive care (recombinant interleukin-7)	Recombinant Interleukin-7	Within 60-180 days after CBT, patients receive recombinant interleukin-7 IM or SC once per week for 3 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicities	Up to 42 days after first injection	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Up to 3 years	Number of participant that survived after 3 years.