Acute Myeloid Leukemia Clinical Trial
— HEMOS AML 0106Official title:
Phase II, Open-Label, Multi-centre, 2-part Study to Assess the Safety, Tolerability, and Efficacy of Tipifarnib Plus Bortezomib in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) Unfit for Conventional Chemotherapy ( >18 Years) or in Patients With Acute Myeloid Leukemia in First Relapse ( >60 Years)
This is one of the first studies of combination of Zarnestra plus Velcade in man. A primary
objective of the study is therefore to assess the safety and tolerability of multiple doses
of Zarnestra plus Velcade in patients with AML.
New treatments for patients that are untreatable with intensive chemotherapy aged de novo
AML patients or post-relapse AML are urgently required since, at present, many of the drugs
used for second line therapy are the same as those used for first induction and response
rates are much lower.
- The following evidence suggests that Velcade plus Zarnestra can be an attractive
therapeutic combination for: AML patients.
- Affymetrix gene profiling data showed expression of NFkB1 in all of 5 myeloid cell
lines cell lines tested and 35% of over 250 patient samples ( data generated in
collaboration with Sergio Ferrari and Pier Paolo Piccaluga unpublished results, our
Institute and University of Modena,Italy)
- Preclinical evidence showed that AML cells in suspension culture were prevented to
develop de novo drug resistance and mediated drug resistance.
In Part B additional patients with AML will be treated to further characterize the
tolerability,biological effects, and clinical efficacy of the combination Velcade plus
Zarnestra. Patients on treatment for AML will undergo regular bone marrow aspirates and
biopsies to assess responses to treatment. This will facilitate frequent assessment of
biological endpoints (reduction in expression and phosphorylation of IKKb kinase, and
downstream markers of signalling along with apoptosis, survival, proliferation and cellular
size and ploidy) will be made in an attempt to confirm that the desired biological activity
has been achieved at the maximum tolerated dose.
Status | Recruiting |
Enrollment | 72 |
Est. completion date | |
Est. primary completion date | |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: 1. Provision of written informed consent 2. Male or female aged >18 years with newly diagnosed Acute Myeloid Leukemia (AML), de novo or secondary, unfit for conventional chemotherapy 3. Male or female with Acute Myeloid Leukemia in first relapse ( > 60 years) 4. WHO performance status ³ 2, or/and unwillingness to receive conventional chemotherapy 5. Negative pregnancy test or evidence of post-menopausal status for female patients. 6. RASGRP1/APTX gene expression ratio calculated at the screening >10 (part B.2 only) Exclusion Criteria: 1. Serum bilirubin 2 x> Upper Limit of Normal (ULN) 2. Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) >3.5 x ULN 3. Serum creatinine ³ 2.5 x ULN or 24-hour creatinine clearance £ 60 mL/min (measured or calculated by Cockcroft-Gault) 4. Patients with AML of FAB M3 classification (APL) 5. Patients with a history of another primary malignancy within the previous 1 year other than basal cell carcinoma or carcinoma in situ, the patient is in remission 6. Any clinically defined central nervous system AML. 7. Participation in an investigational drug study within the 30 days prior to entry 8. Evidence of uncontrolled infection or CNS-Hemorrhagic 9. Patients with documented cases of human immunodeficiency virus (HIV) 10. Peripheral Neuropathy or Neuropathic Pain grade > or = 2 11. Has known or suspected hypersensitivity or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used 12. Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 7,NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis 13. RASGRP1/APTX gene expression ratio calculated at the screening <10 (part B.2 only) |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Italy | Istituto di Ematologia "L e A Seragnoli" Policlinico S.Orsola-Malpighi | Bologna |
Lead Sponsor | Collaborator |
---|---|
University of Bologna | Janssen-Cilag Ltd. |
Italy,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | PART A: Assess the safety and tolerability of combined use of Zarnestra plus multiple ascending doses of Velcade in patients with de novo AML unfit for conventional chemotherapy (age >18 years) or in first or subsequent relapse ( >60 years).(COMPLETED) | August 2007 | No | |
Primary | Part B.1: Assess the effect of Tipifarnib plus the defined in part A dose of Velcade in patients with de novo AML unfit for conventional chemotherapy (age >18 years) or in Patients in first or subsequent relapse ( >60 years) (COMPLETED) | December 2008 | No | |
Primary | Part B.2: Evaluate the overall response (CR, PR, HI) of patients with a RASGRP1/APTX gene expression ratio > 10, identified as predictive of a good clinical response to tipifarnib in patients with de novo AML unfit for conventional chemotherapy. | June 2010 | No | |
Secondary | To investigate the effect of Velcade on the expression of NFkB, and biomarkers of NFkB | |||
Secondary | Including phosphorylation of c-Rel on leukaemic blasts by flow cytometry, protein analysis, | |||
Secondary | Immunohistochemistry, and/or mRNA profiling using gene and SNPs DNA chip. |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05400122 -
Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer
|
Phase 1 | |
Recruiting |
NCT04460235 -
Immunogenicity of an Anti-pneumococcal Combined Vaccination in Acute Leukemia or Lymphoma
|
Phase 4 | |
Completed |
NCT04022785 -
PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
|
Phase 1 | |
Completed |
NCT03678493 -
A Study of FMT in Patients With AML Allo HSCT in Recipients
|
Phase 2 | |
Recruiting |
NCT05424562 -
A Study to Assess Change in Disease State in Adult Participants With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy Receiving Oral Venetoclax Tablets in Canada
|
||
Terminated |
NCT03224819 -
Study of Emerfetamab (AMG 673) in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML)
|
Early Phase 1 | |
Completed |
NCT03197714 -
Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia
|
Phase 1 | |
Active, not recruiting |
NCT04070768 -
Study of the Safety and Efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in Patients With Relapsed or Refractory CD33+ Acute Myeloid Leukemia:Big Ten Cancer Research Consortium BTCRC-AML17-113
|
Phase 1 | |
Active, not recruiting |
NCT03844048 -
An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial
|
Phase 3 | |
Active, not recruiting |
NCT04107727 -
Trial to Compare Efficacy and Safety of Chemotherapy/Quizartinib vs Chemotherapy/Placebo in Adults FMS-like Tyrosine Kinase 3 (FLT3) Wild-type Acute Myeloid Leukemia (AML)
|
Phase 2 | |
Recruiting |
NCT04385290 -
Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)
|
Phase 1/Phase 2 | |
Recruiting |
NCT04920500 -
Bioequivalence of Daunorubicin Cytarabine Liposomes in Naive AML Patients
|
N/A | |
Recruiting |
NCT03897127 -
Study of Standard Intensive Chemotherapy Versus Intensive Chemotherapy With CPX-351 in Adult Patients With Newly Diagnosed AML and Intermediate- or Adverse Genetics
|
Phase 3 | |
Active, not recruiting |
NCT04021368 -
RVU120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome
|
Phase 1 | |
Recruiting |
NCT03665480 -
The Effect of G-CSF on MRD After Induction Therapy in Newly Diagnosed AML
|
Phase 2/Phase 3 | |
Completed |
NCT02485535 -
Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant
|
Phase 1 | |
Enrolling by invitation |
NCT04093570 -
A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers
|
Phase 2 | |
Recruiting |
NCT04069208 -
IA14 Induction in Young Acute Myeloid Leukemia
|
Phase 2 | |
Recruiting |
NCT05744739 -
Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML)
|
Phase 1 | |
Recruiting |
NCT04969601 -
Anti-Covid-19 Vaccine in Children With Acute Leukemia and Their Siblings
|
Phase 1/Phase 2 |