Recombinant Human Interleukin-7 to Promote T-Cell Recovery After Cord Blood Transplant

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03941769

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase I 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 cord blood transplant. 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 cord blood transplant.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Chronic Myelogenous Leukemia, BCR-ABL1 Positive Cord Blood Transplant Recipient Myelodysplastic Syndrome Myeloproliferative Neoplasm	Biological: Recombinant Interleukin-7	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

To determine the safety and establish the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of recombinant interleukin-7 (interleukin 7 [IL-7, CYT107]).

SECONDARY OBJECTIVES:

To determine the rate of cytomegalovirus (CMV), Epstein-Barr virus (EBV) and BK viral infections in cord blood transplant (CBT) patients who receive three doses of IL-7 following engraftment.
To calculate the overall survival (OS), progression-free survival (PFS), and cumulative incidence of graft versus host disease (GVHD) and cumulative incidence of relapse.
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.
To obtain information about the pharmacokinetic (PK) profile of CYT107 by estimating time to maximum concentration (Tmax), concentration maximum (Cmax), half-life, clearance and area-under-the-curve (AUC).

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

21 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

A Phase I Study of Recombinant Human Interleukin-7 to Promote T-Cell Recovery After Cord Blood Transplantation

Actual Study Start Date :

Sep 29, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Supportive care (recombinant interleukin-7) Within 60-180 days after CBT, patients receive recombinant interleukin-7 IM or SC once per week for 3 weeks.	Biological: Recombinant Interleukin-7 Given IM or SC Other Names: CYT 99 007 CYT-107 IL-7 Lymphopoietin-1 Recombinant Human Interleukin-7

Arm

Intervention/Treatment

Experimental: Supportive care (recombinant interleukin-7)

Within 60-180 days after CBT, patients receive recombinant interleukin-7 IM or SC once per week for 3 weeks.

Biological: Recombinant Interleukin-7

Given IM or SC

Other Names:

CYT 99 007

CYT-107

IL-7

Lymphopoietin-1

Recombinant Human Interleukin-7

Outcome Measures

Primary Outcome Measures

Incidence of dose limiting toxicity [Up to 42 days after first injection]
Will be defined as any of the events: 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.
Maximum tolerated dose [Up to 42 days after first injection]
Bayesian model averaging-continual reassessment method will be applied to determine an optimal recommended dose of CYT107.

Secondary Outcome Measures

Rate of viral infections [Up to 3 years]
Will determine the rate of cytomegalovirus, Epstein-Barr virus, and BK viral infections in cord blood transplant patients who receive three doses of CYT107 following engraftment.
Overall survival [Up to 3 years]
Will be estimated using the method of Kaplan and Meier.
Progression-free survival [Up to 12 months from the start of therapy]
Will be estimated using the method of Kaplan and Meier.
Cumulative incidence of GVHD [Up to 3 years]
Cumulative incidence of relapse [Up to 3 years]
T, natural killer (NK), and B cell populations [Up to 3 years]
Effects of CYT107 on the recovery of T, NK, and B cell populations and their functions in vitro will be evaluated.
CYT107 blood levels [Prior to first CYT107 injection and 1, 3, 5, 7, 9, and 24 hours after first injection]
CYT107 blood levels will be submitted to a Model-independent pharmacokinetic analysis allowing to estimate time to maximum concentration, concentration maximum, half-life, clearance and area-under-the-curve.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient post a cord blood transplant (CBT) with documented absolute neutrophil engraftment and no evidence of GVHD or no history of acute or chronic GVHD requiring systemic steroids
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 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
History of Epstein-Barr virus (EBV) associated lymphoproliferation
Active uncontrolled viral, bacterial or fungal infection
Documented human immunodeficiency virus (HIV)-1 or -2, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection at any time before or after transplant. (A positive hepatitis B serology indicative of a previous immunization is not an exclusion criteria)
EBV viremia equal to or greater than 500 copies EBV deoxyribonucleic acid (DNA)/mL of blood by quantitative polymerase chain reaction (PCR)
Positive cytomegalovirus (CMV) antigenemia
History of autoimmune disease
Receiving systemic corticosteroid therapy
Receiving concurrent treatment with another investigational drug and/or biological agent
Receiving anticoagulant therapy
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
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