What side effects are associated with this type of intervention?

Treatments for Non-Hodgkin's Lymphoma that target BCL2 and MCL1 proteins, such as venetoclax and experimental MCL1 inhibitors, commonly cause side effects like neutropenia, infections, tumor lysis syndrome, anemia, and thrombocytopenia. Combining these inhibitors may enhance anti-tumor activity but also increase the risk of compounded side effects.

What prior FDA approvals exist?

Venetoclax, a BCL2 inhibitor, has been FDA-approved for the treatment of certain hematologic malignancies, including chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), which are subtypes of Non-Hodgkin's Lymphoma. While there are no specific FDA-approved MCL1 inhibitors for NHL, ongoing research and clinical trials, such as the VOB560 and MIK665 study, are exploring the potential of targeting both BCL2 and MCL1 proteins to enhance anti-tumor activity in these malignancies.

What other types of research exist?

Promising novel alternatives for Non-Hodgkin's Lymphoma patients include: 1) CAR T-cell therapies such as axicabtagene ciloleucel and tisagenlecleucel, which have shown significant efficacy in relapsed/refractory NHL. 2) Bispecific antibodies like mosunetuzumab, which targets CD20 and CD3, offering a novel mechanism of action. 3) BTK inhibitors such as zanubrutinib and acalabrutinib, which have demonstrated improved tolerability and efficacy in clinical trials. These therapies represent advanced options that may be available for NHL patients in 2024.

← Back to Search

Protein Blocker

VOB560 + MIK665 for Blood Cancer

Phase 1

Waitlist Available

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Diagnosis of relapsed and/or refractory multiple myeloma (MM) treated with at least 2 prior regimens, including an IMiD, a 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

Must not have

History of or current interstitial lung disease or pneumonitis grade ≥ 2

Symptomatic congestive heart failure (New York Heart Association ≥ 3)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at month 18

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two new drugs, VOB560 and MIK665, on patients with certain blood cancers. These drugs aim to block proteins that help cancer cells survive, making it easier for the body to eliminate them.

Who is the study for?

This trial is for adults with certain blood cancers (Non-Hodgkin lymphoma, Multiple Myeloma, or Acute Myeloid Leukemia) that have come back or didn't respond to treatment. They should be fairly active (ECOG ≤2), have measurable disease, and must have tried multiple treatments already. People can't join if they've had severe heart issues, very low blood counts, serious allergies to study drugs' ingredients, recent other cancer therapies, or are suitable for standard re-induction chemotherapy.

What is being tested?

The trial tests a combination of two new drugs: VOB560 and MIK665. These drugs block proteins BCL2 and MCL1 that help cancer cells avoid death. The goal is to find safe doses and see if the drug combo helps patients by causing cancer cells to die off.

What are the potential side effects?

While specific side effects aren't listed here, similar medications often cause symptoms like nausea, fatigue, risk of infection due to low blood cell counts; potential heart problems could also arise given the exclusion criteria related to cardiac health.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am willing and able to undergo multiple bone marrow tests as required.

Select...

My multiple myeloma has returned or didn't respond to treatment, and I've tried at least 2 types of treatment including IMiD, a proteasome inhibitor, and anti-CD38 antibody.

Select...

I can take care of myself but might not be able to do heavy physical work.

Select...

My non-Hodgkin lymphoma has returned or didn't respond to treatment, and I have a measurable tumor.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have or had serious lung inflammation.

Select...

I have severe heart failure symptoms.

Select...

My kidney function is reduced with a creatinine clearance below 50 mL/min.

Select...

I have heart problems or significant ECG abnormalities.

Select...

My liver enzymes are higher than normal.

Select...

My white blood cell count is low due to my cancer treatment.

Select...

My hemoglobin level is below 8 g/dl.

Select...

I had a stem cell transplant within the last 3 months for my NHL or MM.

Select...

My liver and kidney tests are abnormal, but I've never had pancreatitis.

Select...

I have had a stem cell transplant from a donor before starting the study treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at month 18

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at month 18

This trial's timeline: 3 weeks for screening, Varies for treatment, and at month 18 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose intensities

Frequency of dose interruptions

Frequency of dose reductions

+2 more

Secondary study objectives

Apparent volume of distribution (Vz) of MIK665

Apparent volume of distribution (Vz) of VOB560

Area Under Curve (AUC) of MIK665

+12 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: VOB560-MIK665 - Part 2dExperimental Treatment2 Interventions

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

Group II: VOB560-MIK665 - Part 2cExperimental Treatment2 Interventions

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.

Group III: VOB560-MIK665 - Part 2bExperimental Treatment2 Interventions

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.

Group IV: VOB560-MIK665 - Part 2aExperimental Treatment2 Interventions

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.

Group V: VOB560-MIK665 - Part 1bExperimental Treatment2 Interventions

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

Group VI: VOB560-MIK665 - Part 1aExperimental Treatment2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

MIK665

2017

Completed Phase 1

~40

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Hodgkin's Lymphoma (NHL) often target proteins that help cancer cells survive. BCL2 and MCL1 are proteins that prevent cancer cells from undergoing programmed cell death (apoptosis). Treatments like VOB560 and MIK665 are designed to block these proteins, thereby promoting the death of cancer cells. This is crucial for NHL patients because it directly targets the survival mechanisms of the lymphoma cells, potentially leading to more effective eradication of the disease and improved patient outcomes.

Mantle cell lymphoma.