Phase IIA Open Label Study to Evaluate Efficacy and Safety of BL-8040 Followed by (hATG), Cyclosporine and Methyprednisolone in Adult Subjects With Aplastic Anemia or Hypoplastic Myelodysplastic Syndrome

NCT02462252 | Completed Phase 2 DMC

• 1 other identifier: BL-8040.06
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

An open label single arm study to assess efficacy and safety of BL-8040 on top of standard immunotherapy regimen of hATG, cyclosporine and steroids in patients with Hypoplastic MDS and AA over the course of a six month (180 day) treatment period.

Conditions

Aplastic Anemia; Hypoplastic Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Response Rate

  95% confidence interval (CI) will be calculated for subjects who achieve Complete response (CR), Partial response (PR), for all AA and MDS subjects, and hematological improvement (HI) for MDS subjects only. Measurement in percentages (%)

  up to 6 months (180 days)

Secondary Outcomes (7)

• Toxicity

  study treatment duration (180 days) plus 30 days following last dose of last treatment

• general safety

  up to end of study treatment (180 days)

• tolerability

  up to end of end of study treatment (180 days)

• Time to response

  up to 5 years

• Response duration

  up to 5 years

Study Arms (1)

BL-8040 plus hATG, methylprednisolone, cyclosporine

EXPERIMENTAL

BL-8040 0.75mg/kg will be administered Subcutaneously (SC ) on Days 1-10, then on first 5 days of months 2-6. Standard therapy: hATG: Days 11-14: 40mg/kg/day IV over 6-8 hours, in all AA subjects, or in MDS subjects less than 55 years old. 35mg/kg/day IV over 6-8 hours in MDS subjects 55 years and older. Standard therapy: methylprednisolone: Days 11-14: 40mg/kg/day IV over 6-8 hours, in all AA subjects, or in MDS subjects less than 55 years old. 35mg/kg/day IV over 6-8 hours in MDS subjects 55 years and older. Standard therapy: cyclosporine: 5mg/kg/day orally, given in 2 divided doses, starting on day 11 and continuing through Month 6 Day 30 (end of treatment)

Drug: BL-8040; Drug: horse anti-thymocyte globulin (hATG); Drug: Methylprednisolone; Drug: Cyclosporine

Interventions

BL-8040 DRUG

Subjects will receive subcutaneous (SC) injections of BL-8040 monotherapy on days 1-10 of the study. Beginning on Month 2 day 1, (M2/D1), and continuing monthly through Month 6, BL-8040 will be administered daily as part of the maintenance period for the first 5 days of each month.

BL-8040 plus hATG, methylprednisolone, cyclosporine

horse anti-thymocyte globulin (hATG) DRUG

From Day 11 through Day 14 of first month, subjects will receive hATG infusion over 6-8 hours each day.

Also known as: ATGAM

BL-8040 plus hATG, methylprednisolone, cyclosporine

Methylprednisolone DRUG

From Day 11-14 of first month, subjects receive infusion of methylprednisolone 30 minutes prior to hATG infusion. Treatment with methylprednisolone will continue for 30 days. (After day 14, subjects may receive oral prednisone dose equivalent to IV methylprednisolone dose. The oral dose will be tapered off over 30 days.

Also known as: Medrol, Solu-Medrol, Depo-Medrol

BL-8040 plus hATG, methylprednisolone, cyclosporine

Cyclosporine DRUG

From Day 11 through end of treatment (Month 6 Day 30), subjects will receive oral dose of cyclosporine.

Also known as: Sandimmune, Cyclosporine A

BL-8040 plus hATG, methylprednisolone, cyclosporine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult men and women aged 18 and older
• Patient must have the ability to understand the requirements of the study and provide informed consent.
• Patients with the diagnosis of severe AA, who are not currently candidates for an allogeneic stem cell transplant, fulfilling the following criteria:
• BM cellularity \< 30% and
• Peripheral blood (PB) showing at least two of the following criteria:
• Absolute neutrophil count (ANC) \< 0.5 k/µL Platelet count \< 30 k/µL Absolute reticulocyte count \< 60,000/µL
• Patients with recurrent/relapsed AA will be eligible for the trial as long as they were not previously refractory to hATG-based therapy and the relapse occurred \> 3 months after response.
• Patients with Hypoplastic MDS defined as MDS with marrow cellularity of:
• \< 30% for patients \< 60 years,
• \< 20% for patients ≥ 60yrs.
• Patients must have been off of cytotoxic, immunosuppressive (except steroids), or targeted therapy, including standard and investigational treatments for AA, for at least 1 week or 5 half-lives whichever comes later, prior to entering this study, and have recovered from the toxic effects of that therapy to Grade 1 or less.
• Adequate organ function as defined below:
• Liver function:
• a. Total bilirubin \< 2.0 mg/dL (34 µmol/L) b. AST and/or ALT \<3 x ULN
• Kidney function: creatinine \< 2.5 x ULN.

You may not qualify if:

• \. Known allergy or hypersensitivity to any of the test compounds, materials or contraindication to test product.
• \. Patients who have had any major surgical procedure within 14 days of Day 1. BM biopsy is not considered a major surgical procedure.
• \. Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is being treated on this trial.
• \. Seropositive for HIV antibodies (HIV1 and HIV2), Hepatitis C antibody (Hep C Ab) or a Hepatitis B carrier (positive for Hepatitis B surface antigen \[HBsAg\]).
• \. Life expectancy of ≤ 2 months. 6. Subjects with a clinically significant or unstable medical or surgical condition or any other condition that cannot be well-controlled by the allowed medications permitted in the study protocol that would preclude safe and complete study participation, as determined by medical history, physical examinations, ECG, laboratory tests or chest X-ray. Such conditions may include:
• Unstable cardiovascular conditions at Baseline including but not limited to:
• Symptomatic ischemia, or
• Uncontrolled clinically significant conduction abnormalities (e.g., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded); or
• Congestive heart failure (CHF) NYHA Class ≥ 3, or
• Myocardial infarction (MI) within 3 months. • Presence of active, uncontrolled infection. • Known central nervous system illness (e.g., Alzheimer's disease).
• A gastrointestinal disorder that may affect the absorption of study medication.
• Use of alcohol or drug use that may interfere with the patient's ability to participate in the study.
• Unstable psychiatric disorder that would render the patient unable to comply with study requirements.
• Any malignancies in the 3 years prior to Baseline, excluding basal cell carcinoma, in situ malignancy, low-risk prostate cancer, cervical cancer after curative therapy.
• A co-morbid condition that, in the Investigator's opinion, renders the subject at high risk for treatment complications.

Sponsors & Collaborators

• BioLineRx, Ltd.: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

4-fluorobenzoyl-TN-14003; Antilymphocyte Serum; Methylprednisolone; Methylprednisolone Hemisuccinate; Methylprednisolone Acetate; Cyclosporine

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Peptides

Study Officials

• Tapan Kadia, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2015
• First Posted: June 4, 2015
• Study Start: October 1, 2015
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2020
• Last Updated: December 29, 2020

Record last verified: 2020-12

Locations

US (1)