Re: CAL-101 + Rituxan - Dr.Furman

[Guest guest]

To Al Janski,

Re your question about whether CAL-101 is given at the same time as

the eight Rituxan infusions, the answer is yes.

I'm enrolled in the CAL-101 + Rituxan trial, completed the Rituxan

cycles two weeks ago, and am continuing to take CAL-101 twice daily.

I didn't start with bulky nodes or spleen, even though I'm 11q

deleted, so the reduction in nodes is not dramatic, but there has

been reduction. Blood numbers are moderately improved. (If my

interpretation is wrong, Dr. Furman is welcome to correct me.)

I haven't had side effects (except for a cold) and am feeling OK, as

I was when I started the trial.

Hoping for continued and sustained improvements.

Schaffer

NYC

[Guest guest]

, could you please share your before and current blood numbers? For those

of us without bulky nodes, these changes are of great interest.

Thanks

Lynn

> I didn't start with bulky nodes or spleen, even though I'm 11q

> deleted, so the reduction in nodes is not dramatic, but there has

> been reduction. Blood numbers are moderately improved. (If my

> interpretation is wrong, Dr. Furman is welcome to correct me.)

>

> I haven't had side effects (except for a cold) and am feeling OK, as

> I was when I started the trial.

>

> Hoping for continued and sustained improvements.

>

> Schaffer

> NYC

>

[Guest guest]

It is hard to know. Technically, very few patients who meet the criteria for

requiring therapy respond to rituximab. Therefore, almost everyone is

" refractory " to rituximab. This is not to say that there will not be a clinical

benefit.

Regarding CAL-101+rituximab, I suspect there to be some additive or synergistic

effect as the drugs work via two different mechanisms and even target different

compartments (bone marrow versus lymph nodes). We do have excellent data

supporting a synergistic effect of rituximab plus fludarabine, both clinically

and in the lab.

Rick Furman, MD

>

> Dr. Furman, in a case (such as the one described below) in which the

> patient was " mostly refractory " to rituxan prior to treatment with

> CAL-101 + rituxan, do you think the rituxan had effects that aided in

> the disease reduction that was observed for this patient?

>

> Al Janski

>

>

> From: chsngrnbos@...

> Date: Sat, 26 Feb 2011 15:42:23 -0500 (EST)

> Subject: Re: More patients needed in clinical trials

>

> Speaking of clinical trials, and also of CAL 101, maybe this the time to

> update our CAL101+R experience for anyone who may be interested.

> My husband has gone through the 8 R infusions of the trial and is of

> course on the daily CAL101.

>

> He went into the trial with unusually large nodes throughout and long

> experience with R (although mostly refractory to it now after 7 very

> successful

> years). The large nodes and spleen melted away within the first 7 days

> sending the ALC up to around 160 as expected. In the last 7 weeks the ALC

> has now gone down to 16. So he has almost complete clearing of nodes and

> spleen, his blood counts are inching back up to the normal ranges after having

> inched down over the last 8 months since the R stopped working well for

> him.

>

> Of course this is a Phase 1 trial and we will see what the weeks, months,

> and hopefully years ahead will bring. But right now we are very pleased

> because the side effects are none so far, no fatigue, no problems. But the

> nodes are down to nearly normal in 8 weeks, blood counts returning to near

> normal, and no side effects. So far so good.

>

> Beth, husband dx 2001 at age 48, 11Q aggressive, Rituxan monotherapy from

> 2/2003 to 2010, now CAL101+R trial.

>

[Guest guest]

" , could you please share your before and current blood

numbers? For those of us without bulky nodes, these changes are of

great interest. "

Thanks

Lynn

Lynn,

In response to your question, my numbers are below. But don't give

too much significance to them. One person's response means very

little, since there are so many factors that affect how one responds.

Initial counts:

WBC -- 167.0

RBC -- 2.95

plat -- 79

after 8 wks -- 95.4, 3.37, 125

Best,

[Guest guest]

Dr Furman,

You stated : Regarding CAL-101+rituximab, I suspect there to be some

additive or synergistic effect as the drugs work via two different

mechanisms and even target different compartments (bone marrow versus

lymph nodes)..

I understood that rituximab's strength was its ability to target CD20

cells the peripheral blood, and its activity and the results in the

bone marrow were less predictable.

[Guest guest]

Everything is relative. While it is more effective at clearing the blood, it

certainly adds to CAL-101, which is much less effective at clearing the marrow

compared with lymph nodes.

Rick Furman

>

> Dr Furman,

>

> You stated : Regarding CAL-101+rituximab, I suspect there to be some

> additive or synergistic effect as the drugs work via two different

> mechanisms and even target different compartments (bone marrow versus

> lymph nodes)..

>

> I understood that rituximab's strength was its ability to target CD20

> cells the peripheral blood, and its activity and the results in the

> bone marrow were less predictable.

>

>

>

[Guest guest]

Perhaps GA101 and CAL101 would be the ultimate one, two punch?

~chris

[Guest guest]

At 02:05 PM 2/28/2011, Rick Furman wrote:

>While it (Rituxan) is more effective at clearing the blood, it

>certainly adds to CAL-101, which is much less effective at clearing

>the marrow compared with lymph nodes.

Has the detailed scientific evidence for the relative effects of

CAL-101 on CLL cells in nodes vs. in marrow vs. in blood been

published, or have only summaries (e.g. Dec/2010 ASH abstracts) been

published? Is that evidence based only on treatment of

relapsed/refractory patients?

Relapsed/refractory CLL patients are probably more likely to have

more aggressive (treatment-resistant) CLL cell clones than previously

untreated CLL patients. As such, CAL-101 may be more effective in

clearing marrow in untreated patients, especially untreated patients

who slowly progressed to needing treatment.

I seems unless CAL-101 monotherapy is compared with CAL-101 + Rituxan

in treating previously untreated CLL patients, it will not be certain

whether addition of Rituxan provides additional benefit for

quality-of-life endpoints, like progression-free survival, for that

patient subgroup.

Al Janski