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Dose Finding Study Evaluating Safety and Feasibility in Patients With Relapsed or Refractory Myeloid Neoplasms

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02743611
Recruitment Status : Recruiting
First Posted : April 19, 2016
Last Update Posted : June 18, 2018
Information provided by (Responsible Party):
Bellicum Pharmaceuticals

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Myelodysplastic Syndrome Biological: BPX-701 Drug: Rimiducid Phase 1

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Finding Study Evaluating Safety and Feasibility of BPX-701 in Patients With Relapsed or Refractory Myeloid Neoplasms
Actual Study Start Date : April 14, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Arm Intervention/treatment
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

Biological: BPX-701
TCR modified T cells

Drug: Rimiducid
dimerizer that activates suicide gene in TCR modified T cells
Other Name: AP1903

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) and/or recommended expansion dose of BPX-701 measured by dose limiting toxicities (DLT)s [ Time Frame: 30 days post-treatment infusion ]
    To assess the safety and tolerability as defined by dose-limiting toxicities (DLTs) of BPX-701 T cells administered to patients expressing the HLA- A2.01 allele with relapsed or refractory AML or MDS

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.

      1. Relapsed: Bone marrow blasts ≥5 percent; or reappearance of blasts in the blood
      2. Refractory: Failure to achieve complete remission (CR) or complete remission with incomplete blood count recovery (CRi) after induction chemotherapy
    • MDS patients:

      1. High Grade MDS (RAEB-2) with 10-19% blasts, not responding to hypomethylation therapy or
      2. 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.
  • Renal function:

    1. All patients must have a calculated creatinine clearance > 40 mL/min according to Cockcroft-Gault Equation.
    2. 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).

  • Acceptable coagulation status:

    • International normalized Ratio (INR)/ Prothrombin Time (PT) ≤ 1.5 times ULN.
    • Partial thromboplastin time (PTT) < 1.5 times ULN.
  • For fertile men and women, agreement to use effective contraceptive methods during the study and for 3 months after administration of BPX-701.

Exclusion Criteria:

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):

    1. 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.
    2. Presence of significant neurologic or psychiatric disorders impairing the ability to obtain consent.
    3. Uncontrolled bacterial, viral or fungal infection.
    4. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02743611

Contact: Rachel Cook, MD 503-494-9630

United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Rachel Cook, MD    503-494-7386   
United States, Tennessee
Tennessee Oncology Group Not yet recruiting
Nashville, Tennessee, United States, 37203
Contact: William Donnellan, MD1    615-329-7274   
United States, Texas
Texas Transplant Institute Not yet recruiting
San Antonio, Texas, United States, 78229
Contact: Paul Shaughnessy, MD    210-575-7278      
Sponsors and Collaborators
Bellicum Pharmaceuticals
Principal Investigator: Rachel Cook, MD Oregon Health and Science University

Responsible Party: Bellicum Pharmaceuticals Identifier: NCT02743611     History of Changes
Other Study ID Numbers: BP-011
First Posted: April 19, 2016    Key Record Dates
Last Update Posted: June 18, 2018
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bellicum Pharmaceuticals:
Primary Refractory AML
Relapsed AML
Refractory Myeloid Neoplasms

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Leukemia, Myeloid
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions