Trial record 1 of 1 for:
Dose Finding Study Evaluating Safety and Feasibility in Patients With Relapsed or Refractory Myeloid Neoplasms
Verified April 2017 by Bellicum Pharmaceuticals
Information provided by (Responsible Party):
First received: April 11, 2016
Last updated: April 18, 2017
Last verified: April 2017
This study will evaluate patients with relapsed or refractory Acute Myeloid Leukemia (AML) or advanced hypomethylating agent-resistant myelodysplastic syndrome (MDS) who will have autologous immune cells, called T cells, collected via apheresis. The T cells will be reinfused according to a dose-finding schedule after the patient has been identified as having adequate lymphopenia to provide for homeostatic expansion of the adoptively transferred, engineered T cell therapeutic product. As a safety measure, these T cells have been programmed with a self-destruct switch so that they can be destroyed if they start to react against tissues (Graft versus host disease).
Acute Myeloid Leukemia
||Intervention Model: Single Group Assignment
Masking: No masking
Open LabelPrimary Purpose: Treatment
||A Phase I Dose Finding Study Evaluating Safety and Feasibility of BPX-701 in Patients With Relapsed or Refractory Myeloid Neoplasms
Primary Outcome Measures:
| Estimated Enrollment:
| Anticipated Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||December 2019 (Final data collection date for primary outcome measure)
Experimental: BPX-701 and Rimiducid (AP1903)
BPX-701: autologous T cells genetically modified to express αβ T cell receptor reacting with PRAME peptide/human leukocyte antigen (HLA)-A2.01 and containing the suicide switch
Rimiducid (AP1903): administered to induce apoptosis of the BPX-701 T cells in the event of toxicity
TCR modified T cells
dimerizer that activates suicide gene in TCR modified T cells
Other Name: AP1903
This is a single arm, dose escalation/ de-escalation, single US center, unblinded, phase 1 study. Its main goal is to determine the safety and tolerability of the autologous genetically modified T cell (BPX-701) in subjects with relapsed or refractory AML or advanced hypomethylating agent-resistant MDS. Rimiducid (AP1903) will be administrated treat uncontrolled BPX-701 toxicity, such as Cytokine Release Syndrome or severe off-tumor/on-target toxicities.
|Ages Eligible for Study:
||18 Years and older (Adult, Senior)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
- Acute leukemia: Patients with refractory or relapsed AML, other than acute promyelocytic leukemia (APL).
- Patients with a monosomal or complex karyotype may enroll at the time of day 14 biopsy after induction chemotherapy, if residual disease is identified.
- Patients must express HLA-A2.01 and myeloid blasts must express PRAME.
- Absolute lymphocyte count (ALC) > 300/mm^3 or cluster of differentiation (CD)3+ >150 cells/ mm^3.
- Patients who have relapsed and are greater than 100 days after a stem cell transplant are eligible unless they have active GVHD requiring systemic immunosuppressive therapy, defined as a need for > 10 mg prednisone or equivalent/day and active use of a calcineurin inhibitor.
Relapsed or refractory AML or MDS.
AML patients must have > 5% bone marrow blasts at study entry, without alternative causality (e.g. bone marrow regeneration).
a. Relapsed or refractory AML according to the Modified International Working Group Criteria for AML.
- Relapsed: Bone marrow blasts ≥5 percent; or reappearance of blasts in the blood
- Refractory: Failure to achieve complete remission (CR) or complete remission with incomplete blood count recovery (CRi) after induction chemotherapy
- High Grade MDS (RAEB-2) with 10-19% blasts, not responding to hypomethylation therapy or
- RAEB-1 or RAEB-2 MDS recurrence after initial response.
- Age ≥ 18 years.
- Life expectancy of at least 2 months.
- Karnofsky performance status: > 60%.
- Informed consent has been obtained
- Patients who have come off previous cancer therapy for at least 14 days for prior cytotoxic agents, and prior to D0, except when hydroxyurea is given only when needed to control hyperleukocytosis. Persistent clinically significant toxicities from prior chemotherapy must not be greater than Grade 1 (CTCAE 4.03) at the time of enrollment. Salvage/lymphodepleting chemotherapeutic agents may be given up to 3 days prior to T cell reinfusion if necessary to control rapidly growing disease.
- Able to meet local institutional criteria for T cell apheresis collection.
- All patients must have a calculated creatinine clearance > 40 mL/min according to Cockcroft-Gault Equation.
- Routine urinalysis must show no clinically significant abnormalities.
Subject has adequate organ function as measured by:
i. Adequate LFTs: Total bilirubin ≤ 3.0 x the institutional upper normal limits (ULN) with direct bilirubin < 1.6 x ULN.
ii. Alanine transaminase (ALT)/aspartate transaminase (AST) and Alkaline Phosphatase ≤ 5 x ULN.
iii. Cardiac: left ventricular ejection fraction at rest must be ≥ 40%.
iv. Pulmonary: forced expiratory volume (FEV) 1, forced vital capacity (FVC), carbon monoxide diffusing capacity (DLCO) ≥ 50% predicted (corrected for hemoglobin).
Patients who have any of the following are not eligible for enrollment (initiation of BPX-701 infusion) in this study:
- Inadequate lymphocyte count for collection.
- Bovine product allergy.
- History of prior malignancy other than: i) those associated with the current disease, ii) previously treated with a curative intent therapy less than 1 year ago and except superficial skin cancers.
- Participation in any investigational drug study < 28 days prior to D0 (BPX-701 infusion).
- Uncontrolled leptomeningeal leukemic disease.
- Uncontrolled disseminated intravascular coagulation.
Other serious illness or medical conditions, which in the investigator's opinion could hamper patient's understanding of the study, compliance to study treatment, and/or safety or interpretation of study results. These conditions include (but are not restricted to):
- Congestive heart failure or angina pectoris (New York Heart Association Class III or IV) except when it is medically controlled. Uncontrolled hypertension or malignant arrhythmias.
- Presence of significant neurologic or psychiatric disorders impairing the ability to obtain consent.
- Uncontrolled bacterial, viral or fungal infection.
- Known HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) positivity or subject not meeting the selection criteria as defined for the Foundation for the Accreditation of Cell Therapy (FACT) and American Association of Blood Banks (AABB).
- Unwillingness or inability to comply with procedures required in this protocol.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02743611
|Oregon Health & Science University
|Portland, Oregon, United States, 97239 |
|Contact: Rachel Cook, MD 503-494-7386 firstname.lastname@example.org |
History of Changes
|Other Study ID Numbers:
|Study First Received:
||April 11, 2016
||April 18, 2017
|Individual Participant Data
|Plan to Share IPD:
|Studies a U.S. FDA-regulated Drug Product:
|Studies a U.S. FDA-regulated Device Product:
Keywords provided by Bellicum Pharmaceuticals:
Primary Refractory AML
Refractory Myeloid Neoplasms
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on April 26, 2017
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Bone Marrow Diseases