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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Cord Blood Transplant Recipient
• Intervention / Treatment: Biological: Recombinant Interleukin-7

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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-107; CYT 99 007; IL-7; Lymphopoietin-1; 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

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Gheath Al-Atrash, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2020
• Primary Completion (Actual): March 1, 2023
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: May 6, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (Actual): May 8, 2019

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Chronic Disease; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders
• Other Study ID Numbers: 2018-0674 (Other Identifier: M D Anderson Cancer Center); NCI-2019-02124 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01CA061508 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No