Acute Myeloid Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Cord Blood Transplant Recipient, Myelodysplastic Syndrome, Myeloproliferative Neoplasm
Conditions
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.
Interventions
BIOLOGICALRecombinant Interleukin-7
Given IM or SC
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 3 years | Number of participant that survived after 3 years. |
Countries
United States
Participant flow
Recruitment details
Recruitment was done at The University of Texas MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Recombinant Interleukin-7: Given IM or SC | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Supportive Care (Recombinant Interleukin-7) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
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.
Time frame: Up to 42 days after first injection
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Supportive Care (Recombinant Interleukin-7) | Number of Participants With Dose Limiting Toxicities | 0 Participants |
Secondary
Overall Survival
Number of participant that survived after 3 years.
Time frame: Up to 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Supportive Care (Recombinant Interleukin-7) | Overall Survival | 0 Participants |