CIRM-funded clinical trial shows encouraging results for patients with chronic lymphocytic leukemia & mantle cell lymphoma

Illustration courtesy of Oncternal Therapeutics

I often joke that my job here at CIRM is to be the official translator for the stem cell agency. I have to translate complex science into everyday English that people without a science background – that includes me – can understand.

Think I’m joking? Try making sense of this.

See what I mean. If you are a scientist this is not only perfectly clear, it’s also quite exciting. But for the rest of us……..

Actually, it is really quite exciting news. It’s about a CIRM-funded clinical trial being run by Oncternal Therapeutics to treat people with chronic lymphocytic leukemia (CLL), a kind of cancer where our body makes too many white blood cells. The study is using a combination therapy of Cirmtuzumab (a monoclonal antibody named after us because we helped fund its development) and ibrutinib, a conventional therapy used to treat cancers like CLL.

Cirmtuzumab recognizes and then attaches itself to a protein on the surface of cancer stem cells that the cancer needs to survive and spread. This attachment disables the protein (called ROR1) which slows the growth of the leukemia and makes it more vulnerable to anti-cancer drugs like ibrutinib.

In this Phase 1/2 clinical trial 12 patients were given the combination therapy for 24 weeks or more, making them eligible to determine how effective, or ineffective, the therapy is:

  • 11 of the 12 patients had either a partial response – meaning a reduction in the amount of detectable cancer – or a complete response to the treatment – meaning no detectable cancer.
  • None of the patients saw their cancer spread or grow
  • Three of the patients completed a year of treatment and they all showed signs of a complete response including no enlarged lymph nodes and white blood cell counts in the normal range.  

The combination therapy is also being used to treat people with Mantle Cell Lymphoma (MCL), a rare but fast-growing form of blood cancer. The results from this group, while preliminary, are also encouraging. One patient, who had experienced a relapse following a bone marrow transplant, experienced a complete response after three months of cirmtuzumab and ibrutinib.  

The data on the clinical trial was presented at a poster session (that’s the poster at the top of this blog) at the annual meeting of the American Society of Clinical Oncology.

In a news release Dr. James Breitmeyer, the President & CEO of Oncternal, said the results are very encouraging:  

“These data presented today, taken together with an earlier Phase 1 study of cirmtuzumab as a monotherapy in relapsed/refractory CLL, give us increased confidence in the potential for cirmtuzumab as a treatment for patients with ROR1-expressing lymphoid malignancies, particularly in combination with ibrutinib as a potential treatment for patients with CLL and MCL. We believe that the data also help to validate the importance of ROR1 as a therapeutic target,”

Confusing cancer to kill it

Kipps

Thomas Kipps, MD, PhD: Photo courtesy UC San Diego

Confusion is not a state of mind that we usually seek out. Being bewildered is bad enough when it happens naturally, so why would anyone actively pursue it? But now some researchers are doing just that, using confusion to not just block a deadly blood cancer, but to kill it.

Today the CIRM Board approved an investment of $18.29 million to Dr. Thomas Kipps and his team at UC San Diego to use a one-two combination approach that we hope will kill Chronic Lymphocytic Leukemia (CLL).

This approach combines two therapies, cirmtuzumab (a monoclonal antibody developed with CIRM funding, hence the name) and Ibrutinib, a drug that has already been approved by the US Food and Drug Administration (FDA) for patients with CLL.

As Dr. Maria Millan, our interim President and CEO, said in a news release, the need for a new treatment is great.

“Every year around 20,000 Americans are diagnosed with CLL. For those who have run out of treatment options, the only alternative is a bone marrow transplant. Since CLL afflicts individuals in their 70’s who often have additional medical problems, bone marrow transplantation carries a higher risk of life threatening complications. The combination approach of  cirmtuzumab and Ibrutinib seeks to offer a less invasive and more effective alternative for these patients.”

Ibrutinib blocks signaling pathways that leukemia cells need to survive. Disrupting these pathways confuses the leukemia cell, leading to its death. But even with this approach there are cancer stem cells that are able to evade Ibrutinib. These lie dormant during the therapy but come to life later, creating more leukemia cells and causing the cancer to spread and the patient to relapse. That’s where cirmtuzumab comes in. It works by blocking a protein on the surface of the cancer stem cells that the cancer needs to spread.

It’s hoped this one-two punch combination will kill all the cancer cells, increasing the number of patients who go into complete remission and improve their long-term cancer control.

In an interview with OncLive, a website focused on cancer professionals, Tom Kipps said Ibrutinib has another advantage for patients:

“The patients are responding well to treatment. It doesn’t seem like you have to worry about stopping therapy, because you’re not accumulating a lot of toxicity as you would with chemotherapy. If you administered chemotherapy on and on for months and months and years and years, chances are the patient wouldn’t tolerate that very well.”

The CIRM Board also approved $5 million for Angiocrine Bioscience Inc. to carry out a Phase 1 clinical trial testing a new way of using cord blood to help people battling deadly blood disorders.

The standard approach for this kind of problem is a bone marrow transplant from a matched donor, usually a family member. But many patients don’t have a potential donor and so they often have to rely on a cord blood transplant as an alternative, to help rebuild and repair their blood and immune systems. However, too often a single cord blood donation does not have enough cells to treat an adult patient.

Angiocrine has developed a product that could help get around that problem. AB-110 is made up of cord blood-derived hematopoietic stem cells (these give rise to all the other types of blood cell) and genetically engineered endothelial cells – the kind of cell that lines the insides of blood vessels.

This combination enables the researchers to take cord blood cells and greatly expand them in number. Expanding the number of cells could also expand the number of patients who could get these potentially life-saving cord blood transplants.

These two new projects now bring the number of clinical trials funded by CIRM to 35. You can read about the other 33 here.