VOB560-MIK665 Combination First in Human Trial in Patients With Hematological Malignancies (Relapsed/Refractory Non-Hodgkin Lymphoma, Relapsed/Refractory Acute Myeloid Leukemia, or Relapsed/Refractory Multiple Myeloma)

Study Purpose

The purpose of the study is to identify doses and schedules of VOB560 and MIK665 that can be safely given and to learn if the combination can have possible benefits for patients with Non-Hodgkin lymphoma (NHL), Multiple Myeloma (MM) or Acute Myeloid Leukemia (AML). VOB560 and MIK665 are selective and potent blockers respectively of the B-cell lymphoma 2 (BCL2) protein and of the myeloid cell leukaemia 1 (MCL1) protein, proteins that may protect tumor cells from undergoing cell death. VOB560 and MIK665 are designed to block the functions of the BCL2 and MCL1 proteins, so that the tumor cells that rely on these proteins undergo cell death. Preclinical data suggest that concomitant treatment with VOB560 in combination with MIK665 induces robust anti-tumor activity.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Diagnosis of one of the following hematologic malignancies: - relapsed and/or refractory patients with non-Hodgkin lymphoma with radiographically measurable disease with a clearly demarcated nodal lesion at least 1.5 cm in its largest dimension or a target extra nodal lesion at least 1.0 cm in its largest dimension.
  • - relapsed and/or refractory patients with MM treated with at least 2 prior regimens, including an IMiD, a proteasome inhibitor proteasome inhibitor, and anti-CD38 antibody (if available) and not eligible for treatment with other regimens known to provide clinical benefit, as determined by the investigator.
  • - relapsed and/or refractory patients with Acute Myeloid Leukemia (AML), pathologically confirmed diagnosis as defined by the WHO Classification and with ≥ 5% blasts in bone marrow.
Following ≥ 1 prior therapies who have relapsed or exhibited refractory disease (primary failure) and are deemed by the investigator not to be candidates for standard therapy, including re-induction with cytarabine or other established therapeutic regimens for patients with AML (patients who are suitable for standard re-induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded).
  • - Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
  • - Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institution's guidelines and be willing to undergo a bone marrow aspirate and/or biopsy at screening, during and at the end of therapy on this study.

Exclusion Criteria:

1. History of severe hypersensitivity reactions to any ingredient of study treatment and/or their excipients. 2. Systemic antineoplastic therapy (including cytotoxic chemotherapy, alpha-interferon, kinase inhibitors or other targeted small molecules, and toxin immunoconjugates) or any experimental therapy within 14 days or 5 half-lives, whichever is shorter, before the first dose of study treatment. 3. High-risk patients for Tumor Lysis Syndrome according to Cairo et al 2010 criteria or local guidelines. 4. Impaired cardiac function or clinically significant cardiac disease, or history or current diagnosis of ECG abnormalities indicating significant risk of safety including any of the following: 1. Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second- or third-degree AV block without a pacemaker. 2. Any history of clinical important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block. 3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, significant hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age. 4. Resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment. 5. Use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of study. 6. Abnormal echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) at baseline (left ventricular ejection fraction [LVEF] <50%) 7. Symptomatic congestive heart failure (New York Heart Association ≥ 3) 8. Findings observed in the baseline cardiac MRI that might reflect an increased risk for cardiac adverse events. 5. Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF), thrombopoietin mimetics or erythroid stimulating agents ≤ 2 weeks prior to start of study treatment. If thrombopoietin mimetics or erythroid stimulating agents were initiated more than 2 weeks prior to the first dose of study treatment and the patient is on a stable dose, they can be maintained. 6. For AML patients: Peripheral blast counts > 25,000 blasts / mm3. Patients can receive hydroxyurea to control the peripheral blast counts as long as hydroxyurea can be stopped at least 24 hours prior to obtaining PD biomarkers at screening/baseline. Hydroxyurea can be restarted after sampling if clinically indicated to control blasts prior to the start of study treatment markers. 7. For patients with R/R NHL and R/R MM:
  • - Absolute Neutrophil count < 1.0 x 109/L.
  • - Platelets count < 50 x 109/ L.
  • - Hemoglobin < 8 g/dl.
8. Autologous stem cell transplant within 3 months before the first dose of study treatment. 9. Patients who have undergone a prior allogeneic stem cell transplant before the first dose of study treatment. 10. History of or current interstitial lung disease or pneumonitis grade ≥ 2. 11. Impaired hepatic and renal function defined as:
  • - Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 1.5 x upper limit of normal (ULN) - Bilirubin >1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin) - Creatinine clearance <50 mL/min (calculated using Cockroft-Gault formula, or measured).
12. Lipase >1.5 x ULN or serum amylase >1.5 x ULN and no history of pancreatitis. 13. Increased cardiac troponin above the manufacturer's 99th percentile upper reference limit for local assay at screening. Other protocol-defined inclusion/exclusion criteria may apply

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04702425
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Novartis Pharmaceuticals
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Belgium, Finland, Germany, Hong Kong, Israel, Italy, Japan, Korea, Republic of, Spain, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Non-Hodgkin Lymphoma (NHL), Acute Myeloid Leukemia (AML), Multiple Myeloma (MM)
Arms & Interventions

Arms

Experimental: VOB560-MIK665 - Part 1a

Part 1a - Patients with relapsed/refractory non-Hodgkin lymphoma and relapsed/refractory multiple myeloma administered VOB560 and MIK665 as an intravenous (IV) infusion.

Experimental: VOB560-MIK665 - Part 1b

Part 1b - Patients with relapsed/refractory acute myeloid leukemia administered VOB560 and MIK665 as an intravenous (IV) infusion.

Experimental: VOB560-MIK665 - Part 2a

Part 2a - Patients with relapsed/refractory multiple myeloma with at least 10 patients with 1q gain cytogenetic abnormality and 10 patients with high risk R/R MM as defined in (Sonneveld et al 2016) administered VOB560 and MIK665 as an intravenous (IV) infusion.

Experimental: VOB560-MIK665 - Part 2b

Part 2b - Patients with relapsed/refractory non-Hodgkin lymphoma with at least 10 patients with double-hit (DH) lymphoma, based on the overall bad prognosis and limited therapeutic options for patients with DH NHL administered VOB560 and MIK665 as an intravenous (IV) infusion.

Experimental: VOB560-MIK665 - Part 2c

Part 2c - Patients with relapsed/refractory acute myeloid leukemia venetoclax refractory or insensitive with at least 6 patients M5 as proposed by French-American-British (FAB) group, based on the observation that venetoclax resistance in AML M5 can be caused by up-regulation of MCL1 administered VOB560 and MIK665 as an intravenous (IV) infusion.

Experimental: VOB560-MIK665 - Part 2d

Part 2d - Patients with relapsed/refractory acute myeloid leukemia venetoclax naive patients administered VOB560 and MIK665 as an intravenous (IV) infusion.

Interventions

Drug: - VOB560

Powder for concentrate for solution for infusion

Drug: - MIK665

Concentrate for solution for infusion

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

New Haven, Connecticut

Status

Recruiting

Address

Yale University School of Medicine Smilow Cancer Hospital

New Haven, Connecticut, 06520

Site Contact

Christine Ly

christine.ly@yale.edu

203-737-1906

University of Michigan, Ann Arbor, Michigan

Status

Recruiting

Address

University of Michigan

Ann Arbor, Michigan, 48109

Site Contact

Nancy McCullough

ntsai@med.umich.edu

+1 734 232 1486

Houston, Texas

Status

Recruiting

Address

Uni of TX MD Anderson Cancer Cntr UT MD Anderson Cancer Ctr

Houston, Texas, 77030

Site Contact

Habiba Halim

HHalim@mdanderson.org

713-745-3246

International Sites

Novartis Investigative Site, Gent, Belgium

Status

Recruiting

Address

Novartis Investigative Site

Gent, , 9000

Novartis Investigative Site, HUS, Finland

Status

Recruiting

Address

Novartis Investigative Site

HUS, , FIN-00029

Novartis Investigative Site, Heidelberg, Germany

Status

Recruiting

Address

Novartis Investigative Site

Heidelberg, , 69120

Novartis Investigative Site, Ulm, Germany

Status

Recruiting

Address

Novartis Investigative Site

Ulm, , 89081

Novartis Investigative Site, Hong Kong, Hong Kong

Status

Recruiting

Address

Novartis Investigative Site

Hong Kong, ,

Novartis Investigative Site, Tel Aviv, Israel

Status

Recruiting

Address

Novartis Investigative Site

Tel Aviv, , 6423906

Novartis Investigative Site, Rozzano, MI, Italy

Status

Recruiting

Address

Novartis Investigative Site

Rozzano, MI, 20089

Novartis Investigative Site, Sunto Gun, Shizuoka, Japan

Status

Recruiting

Address

Novartis Investigative Site

Sunto Gun, Shizuoka, 411 8777

Novartis Investigative Site, Seoul, Korea, Republic of

Status

Recruiting

Address

Novartis Investigative Site

Seoul, , 03080

Novartis Investigative Site, Santander, Cantabria, Spain

Status

Recruiting

Address

Novartis Investigative Site

Santander, Cantabria, 39008

Novartis Investigative Site, Salamanca, Castilla Y Leon, Spain

Status

Recruiting

Address

Novartis Investigative Site

Salamanca, Castilla Y Leon, 37007