Re: I would like to discuss a study option

April 24, 2005

HI Cheryl,

This is awsome news!!! Does this actually mean what i think it may mean???? A

possible cure around the horizon!!! Even if it isn't it is very promising and

they are sure to find a cure soon!!! I agree if it is Dr. Drucker then it looks

even better!!!

Hoping all is well with you!!

Take care.

Love Penny

Cheryl-Anne Simoneau <cheryl.simoneau@...> wrote:

Hello All,

I noticed the clinical trial information posted below on the Asian List and

I would like to have some discussion about it.

The trial is being conducted by Dr. B. Druker and it involves combining IFN

and IM. The interesting part is that depending on the response, IFN is

dropped after the first year and if a molecular remission is achieved and

held (PCRU) for two years based on bone marrow testing, IM is also dropped.

Obviously this is quite appealing to me, as I tolerated IFN so well. The

thought of a clinical trial being designed to reach an " end point " of no

further medications is incredibly exciting; particularly so because Dr. D.

is the PI.

So, below is the information on the trial. My questions are:

If you could enroll in this trial, would you?

Is there anyone among us who is on this trial?

What are any drawbacks that someone should think about with regards to this

trial?

Any general comments and your kind insight would be most helpful to me.

Warm wishes to everyone,

Cheryl-Anne

Imatinib Mesylate and Interferon Alfa in Treating Patients With

Chronic Myelogenous Leukemia

This study is currently recruiting patients.

Sponsors and Collaborators: Oregon Health and Science University

National Cancer Institute (NCI)

Information provided by: National Cancer Institute (NCI)

Purpose

RATIONALE: Imatinib mesylate and interferon alfa may interfere with

the growth of the cancer cells. Combining imatinib mesylate with

interferon alfa may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining

imatinib mesylate with interferon alfa in treating patients who have

chronic myelogenous leukemia.

Condition Treatment or Intervention Phase

relapsing chronic myelogenous leukemia

chronic phase chronic myelogenous leukemia

Philadelphia chromosome positive chronic myelogenous leukemia

Drug: imatinib mesylate

Drug: interferon alfa

Procedure: biological response modifier therapy

Procedure: cytokine therapy

Procedure: enzyme inhibitor therapy

Procedure: interferon therapy

Procedure: protein tyrosine kinase inhibitor therapy

Phase II

MedlinePlus related topics: Leukemia, Adult Acute; Leukemia, Adult

Chronic; Leukemia, Childhood

Study Type: Interventional

Study Design: Treatment

Official Title: Phase II Study of Imatinib Mesylate and Interferon

alfa in Patients With Chronic Phase Chronic Myelogenous Leukemia

Further Study Details:

OBJECTIVES:

Determine the maximum tolerated dose of interferon alfa administered

with imatinib mesylate in patients with chronic phase chronic

myelogenous leukemia. (Phase I closed to accrual as of 7/9/03.)

Determine the safety and tolerability of this regimen in this patient

population.

Determine the complete, major, and minor cytogenetic response rates

and complete hematologic response rate in patients after 6 and 12

months of treatment with this regimen.

Determine the molecular response (reverse transcriptase-polymerase

chain reaction for bcr-abl) rate in patients who have a complete

cytogenetic response after 6 and 12 months of treatment with this

regimen.

Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive oral imatinib mesylate once daily beginning on day 1

and interferon alfa (IFN-A) subcutaneously once daily or 3 times

weekly beginning on day 14. Courses repeat every 35 days for up to 1

year in the absence of disease progression or unacceptable toxicity.

After completion of 1 year of therapy, patients may receive

additional therapy, provided that the patient is benefiting from

imatinib mesylate. IFN-A is discontinued in patients who achieve a

molecular remission that is confirmed on 2 successive bone marrow

samples. Imatinib mesylate is discontinued in patients who achieve

and maintain a molecular remission for 2 years. Sequential dose

escalation of IFN-A is followed by sequential dose escalation of

imatinib mesylate. Cohorts of 3-6 patients receive escalating doses

of IFN-A and then imatinib mesylate until the maximum tolerated dose

(MTD) of the combination is determined. The MTD is defined as the

dose preceding that at which 2 of 6 patients experience dose-limiting

toxicity.

Phase II: Patients receive imatinib mesylate and IFN-A as in phase I

at the established MTD. Patients are followed for 30 days.

PROJECTED ACCRUAL: Approximately 3-15 patients will be accrued for

the phase I portion of this study. (Phase I closed to accrual as of

7/9/03.) A total of 40 patients will be accrued for the phase II

portion of the study within 3-4 months.

Eligibility

Ages Eligible for Study: 18 Years and above, Genders Eligible for

Study: Both

Criteria

DISEASE CHARACTERISTICS:

Cytogenetically confirmed chronic myelogenous leukemia (CML)

Less than 15% blasts in peripheral blood or bone marrow

Less than 30% blasts and promyelocytes in peripheral blood or bone

marrow

Less than 20% basophils in blood or bone marrow

Platelet count at least 100,000/mm^3

No leukemia beyond bone marrow, blood, liver, or spleen

No chloroma

Philadelphia (Ph) chromosome-positive CML in chronic phase

Newly diagnosed Ph chromosome-positive CML in chronic phase

Initial diagnosis within 6 months of study

No prior therapy for CML except hydroxyurea and/or anagrelide

hydrochloride

No identified sibling donors where allogeneic stem cell

transplantation is elected as first-line therapy

PATIENT CHARACTERISTICS: Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics

Hepatic:

Bilirubin no greater than 1.5 times upper limit of normal (ULN)

AST or ALT no greater than 2 times ULN

Renal:

Creatinine no greater than 1.5 times ULN

Cardiovascular:

No New York Heart Association class III or IV heart disease

Other:

Not pregnant or nursing

Negative pregnancy test

Fertile patients must use 2 methods of effective barrier

contraception during and for at least 3 months after study

participation

No other serious uncontrolled medical condition

No autoimmune disease

No prior noncompliance to medical regimens or potential unreliability

No prior grade 3 or greater non-hematologic toxicity due to prior

interferon (phase I [closed to accrual as of 7/9/03])

PRIOR CONCURRENT THERAPY: Biologic therapy:

See Disease Characteristics

No prior bone marrow or peripheral blood stem cell transplantation

At least 2 weeks since prior interferon alfa (phase I [closed to

accrual as of 7/9/03])

Chemotherapy:

See Disease Characteristics

At least 6 weeks since prior busulfan (phase I [closed to accrual as

of 7/9/03] )

At least 2 weeks since prior cytarabine (phase I [closed to accrual

as of 7/9/03])

No concurrent chemotherapy

Concurrent hydroxyurea allowed during the first 3 months of study

Endocrine therapy:

Not specified

Radiotherapy:

Not specified

Surgery:

Not specified

Other:

At least 4 weeks since prior investigational agents other than

imatinib mesylate (phase I [closed to accrual as of 7/9/03])

No concurrent grapefruit juice

Concurrent anagrelide hydrochloride allowed during the first 3 months

of study

Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier

NCT00015847

Illinois

H. Lurie Comprehensive Cancer Center at Northwestern

University, Chicago, Illinois, 60611, United States; Recruiting

Stuart Tallman, MD 312-695-4540

Oregon

Cancer Institute at Oregon Health and Science University,

Portland, Oregon, 97239, United States; Recruiting

Jay Druker, MD 503-494-5596

Study chairs or principal investigators

Jay Druker, MD, Study Chair, Oregon Health and Science

University

More Information

Clinical trial summary from the National Cancer Institute's PDQR

database

Study ID Numbers: CDR0000068443; OHSU-6263; NCI-2794; NCT00015847

Record last reviewed: March 2005

Last Updated: March 10, 2005

April 25, 2005

>

>Cheryl-Anne Simoneau <cheryl.simoneau@...> wrote:

>

>Hello All,

>

>I noticed the clinical trial information posted below on the Asian List and

>I would like to have some discussion about it.

>

>The trial is being conducted by Dr. B. Druker and it involves combining IFN

>and IM. The interesting part is that depending on the response, IFN is

>dropped after the first year and if a molecular remission is achieved and

>held (PCRU) for two years based on bone marrow testing, IM is also dropped.

>Obviously this is quite appealing to me, as I tolerated IFN so well. The

>

>Cheryl-Anne

Hi Cheryl-Anne,

I do not have particular info about this trial, but it does not surprise

me. I believe that has been doing this with Dr. Mauro for some time

now....to try to get off drugs. She will probably respond.

It makes sense.....because some with a good response to inf do have a

durable remission and can stop taking meds. So the IM is kind of helping to

get you to PCRU and safely holding you there for a period of time....

then you see if the period of inf. 'jolted' the immune system enough to

give you a durable remission without drugs.

I think that Geri might have asked OHSU about doing this treatment but I

believe she did not qualify because she is post-BMT (at least she could not

be in a trial).

Dr. Druker has told me before that for a cure he thinks something will have

to affect the immune system (to kill cml cells as they arise).....

at that time he was mentioning a possible vaccine (if an effective one can

be developed).

Because you tolerated inf so well, I would think this is something for you

to look into.

C.

April 25, 2005

Hello Penny,

I don't know what to say about this, although it does sound rather

hopeful. However in light of the information last week about the

nasty " death cell " capacity of the CML stem Cells, I am thinking

that because IFN is a biological modifier (not new info, we've

always known this) then that is why it has worked in some

instances. The combination of IM and IFN kill off enough if not all

in some cases of these CML death stem cells. The problem in the

past has always been the high toxicity of IFN and the unfortunae

capacity of the body to build up resistance to it. So maybe in this

case IM and IFN can be an effective one-two punch, but it might not

work for all.

How are you doing down in the Caymans? How is the rebuilding of

your home coming along? Have you been able to meet my cousin? She

has been so busy, and I have been out of touch with her, I shall

write to her later on this eveing.

I am doing well. Hope to get results from my last BMB a few weeks

ago to see if I am holding my PCRU status.

Good to hear from you,

Cheers,

Cheryl-Anne

>

> Hello All,

>

> I noticed the clinical trial information posted below on the Asian

List and

> I would like to have some discussion about it.

>

> The trial is being conducted by Dr. B. Druker and it involves

combining IFN

> and IM. The interesting part is that depending on the response,

IFN is

> dropped after the first year and if a molecular remission is

achieved and

> held (PCRU) for two years based on bone marrow testing, IM is also

dropped.

> Obviously this is quite appealing to me, as I tolerated IFN so

well. The

> thought of a clinical trial being designed to reach an " end point "

of no

> further medications is incredibly exciting; particularly so

because Dr. D.

> is the PI.

>

> So, below is the information on the trial. My questions are:

>

> If you could enroll in this trial, would you?

>

> Is there anyone among us who is on this trial?

>

> What are any drawbacks that someone should think about with

regards to this

> trial?

>

> Any general comments and your kind insight would be most helpful

to me.

>

> Warm wishes to everyone,

> Cheryl-Anne

>

> Imatinib Mesylate and Interferon Alfa in Treating Patients With

> Chronic Myelogenous Leukemia

>

> This study is currently recruiting patients.

>

> Sponsors and Collaborators: Oregon Health and Science University

> National Cancer Institute (NCI)

> Information provided by: National Cancer Institute (NCI)

>

> Purpose

>

> RATIONALE: Imatinib mesylate and interferon alfa may interfere with

> the growth of the cancer cells. Combining imatinib mesylate with

> interferon alfa may kill more cancer cells.

>

> PURPOSE: Phase II trial to study the effectiveness of combining

> imatinib mesylate with interferon alfa in treating patients who

have

> chronic myelogenous leukemia.

>

> Condition Treatment or Intervention Phase

> relapsing chronic myelogenous leukemia

> chronic phase chronic myelogenous leukemia

> Philadelphia chromosome positive chronic myelogenous leukemia

> Drug: imatinib mesylate

> Drug: interferon alfa

> Procedure: biological response modifier therapy

> Procedure: cytokine therapy

> Procedure: enzyme inhibitor therapy

> Procedure: interferon therapy

> Procedure: protein tyrosine kinase inhibitor therapy

> Phase II

>

> MedlinePlus related topics: Leukemia, Adult Acute; Leukemia, Adult

> Chronic; Leukemia, Childhood

>

> Study Type: Interventional

> Study Design: Treatment

>

> Official Title: Phase II Study of Imatinib Mesylate and Interferon

> alfa in Patients With Chronic Phase Chronic Myelogenous Leukemia

>

> Further Study Details:

>

> OBJECTIVES:

>

> Determine the maximum tolerated dose of interferon alfa

administered

> with imatinib mesylate in patients with chronic phase chronic

> myelogenous leukemia. (Phase I closed to accrual as of 7/9/03.)

> Determine the safety and tolerability of this regimen in this

patient

> population.

> Determine the complete, major, and minor cytogenetic response rates

> and complete hematologic response rate in patients after 6 and 12

> months of treatment with this regimen.

> Determine the molecular response (reverse transcriptase-polymerase

> chain reaction for bcr-abl) rate in patients who have a complete

> cytogenetic response after 6 and 12 months of treatment with this

> regimen.

> Determine the pharmacokinetics of this regimen in these patients.

> OUTLINE: This is a dose-escalation, multicenter study.

>

> Patients receive oral imatinib mesylate once daily beginning on

day 1

> and interferon alfa (IFN-A) subcutaneously once daily or 3 times

> weekly beginning on day 14. Courses repeat every 35 days for up to

1

> year in the absence of disease progression or unacceptable

toxicity.

> After completion of 1 year of therapy, patients may receive

> additional therapy, provided that the patient is benefiting from

> imatinib mesylate. IFN-A is discontinued in patients who achieve a

> molecular remission that is confirmed on 2 successive bone marrow

> samples. Imatinib mesylate is discontinued in patients who achieve

> and maintain a molecular remission for 2 years. Sequential dose

> escalation of IFN-A is followed by sequential dose escalation of

> imatinib mesylate. Cohorts of 3-6 patients receive escalating doses

> of IFN-A and then imatinib mesylate until the maximum tolerated

dose

> (MTD) of the combination is determined. The MTD is defined as the

> dose preceding that at which 2 of 6 patients experience dose-

limiting

> toxicity.

> Phase II: Patients receive imatinib mesylate and IFN-A as in phase

I

> at the established MTD. Patients are followed for 30 days.

> PROJECTED ACCRUAL: Approximately 3-15 patients will be accrued for

> the phase I portion of this study. (Phase I closed to accrual as of

> 7/9/03.) A total of 40 patients will be accrued for the phase II

> portion of the study within 3-4 months.

>

> Eligibility

>

> Ages Eligible for Study: 18 Years and above, Genders Eligible for

> Study: Both

>

> Criteria

>

> DISEASE CHARACTERISTICS:

>

> Cytogenetically confirmed chronic myelogenous leukemia (CML)

> Less than 15% blasts in peripheral blood or bone marrow

> Less than 30% blasts and promyelocytes in peripheral blood or bone

> marrow

> Less than 20% basophils in blood or bone marrow

> Platelet count at least 100,000/mm^3

> No leukemia beyond bone marrow, blood, liver, or spleen

> No chloroma

> Philadelphia (Ph) chromosome-positive CML in chronic phase

> Newly diagnosed Ph chromosome-positive CML in chronic phase

> Initial diagnosis within 6 months of study

> No prior therapy for CML except hydroxyurea and/or anagrelide

> hydrochloride

> No identified sibling donors where allogeneic stem cell

> transplantation is elected as first-line therapy

> PATIENT CHARACTERISTICS: Age:

>

> 18 and over

> Performance status:

>

> ECOG 0-2

> Life expectancy:

>

> Not specified

> Hematopoietic:

>

> See Disease Characteristics

> Hepatic:

>

> Bilirubin no greater than 1.5 times upper limit of normal (ULN)

> AST or ALT no greater than 2 times ULN

> Renal:

>

> Creatinine no greater than 1.5 times ULN

> Cardiovascular:

>

> No New York Heart Association class III or IV heart disease

> Other:

>

> Not pregnant or nursing

> Negative pregnancy test

> Fertile patients must use 2 methods of effective barrier

> contraception during and for at least 3 months after study

> participation

> No other serious uncontrolled medical condition

> No autoimmune disease

> No prior noncompliance to medical regimens or potential

unreliability

> No prior grade 3 or greater non-hematologic toxicity due to prior

> interferon (phase I [closed to accrual as of 7/9/03])

> PRIOR CONCURRENT THERAPY: Biologic therapy:

>

> See Disease Characteristics

> No prior bone marrow or peripheral blood stem cell transplantation

> At least 2 weeks since prior interferon alfa (phase I [closed to

> accrual as of 7/9/03])

> Chemotherapy:

>

> See Disease Characteristics

> At least 6 weeks since prior busulfan (phase I [closed to accrual

as

> of 7/9/03] )

> At least 2 weeks since prior cytarabine (phase I [closed to accrual

> as of 7/9/03])

> No concurrent chemotherapy

> Concurrent hydroxyurea allowed during the first 3 months of study

> Endocrine therapy:

>

> Not specified

> Radiotherapy:

>

> Not specified

> Surgery:

>

> Not specified

> Other:

>

> At least 4 weeks since prior investigational agents other than

> imatinib mesylate (phase I [closed to accrual as of 7/9/03])

> No concurrent grapefruit juice

> Concurrent anagrelide hydrochloride allowed during the first 3

months

> of study

>

> Location and Contact Information

>

> Please refer to this study by ClinicalTrials.gov identifier

> NCT00015847

>

> Illinois

> H. Lurie Comprehensive Cancer Center at Northwestern

> University, Chicago, Illinois, 60611, United States; Recruiting

> Stuart Tallman, MD 312-695-4540

>

> Oregon

> Cancer Institute at Oregon Health and Science University,

> Portland, Oregon, 97239, United States; Recruiting

> Jay Druker, MD 503-494-5596

>

> Study chairs or principal investigators

>

> Jay Druker, MD, Study Chair, Oregon Health and Science

> University

> More Information

>

> Clinical trial summary from the National Cancer Institute's PDQR

> database

>

> Study ID Numbers: CDR0000068443; OHSU-6263; NCI-2794; NCT00015847

> Record last reviewed: March 2005

> Last Updated: March 10, 2005

>

April 25, 2005

Hi ,

Thanks so much for chiming in on this, your insight is always

helpful.

I know was doing this for a while mixed in also with C-GSF,

and since she has stopped in Janary she is now showing slightly

positive on a PCRU. This is where it gets a bit tricky. There is

something like 17% of the " normal " population that tests positive

for BCR-ABL on a sensitive test, so, I wonder if she really is

positive - but given the history one could argue that is much better

to be safe than sorry.

I wonder what the results are from the Phase I trial? Do you think

you might be able to ask him about this when you are next in to see

him?

Thanks agian for your input.

Warm wishes,

Cheryl-Anne

> Hi Cheryl-Anne,

>

> I do not have particular info about this trial, but it does not

surprise

> me. I believe that has been doing this with Dr. Mauro for

some time

> now....to try to get off drugs. She will probably respond.

>

> It makes sense.....because some with a good response to inf do

have a

> durable remission and can stop taking meds. So the IM is kind of

helping to

> get you to PCRU and safely holding you there for a period of

time....

> then you see if the period of inf. 'jolted' the immune system

enough to

> give you a durable remission without drugs.

>

> I think that Geri might have asked OHSU about doing this treatment

but I

> believe she did not qualify because she is post-BMT (at least she

could not

> be in a trial).

>

> Dr. Druker has told me before that for a cure he thinks something

will have

> to affect the immune system (to kill cml cells as they arise).....

> at that time he was mentioning a possible vaccine (if an effective

one can

> be developed).

>

> Because you tolerated inf so well, I would think this is something

for you

> to look into.

>

> C.

>

April 25, 2005

Hi Cheryl,

Thanks for bringing this to our attention. I share your excitement about

this trial, along with your reasons for it. Since we'll never be able to

measure zero CML, an endpoint of stopping all drugs is the one we must

ultimately get to. Who better than to try it first than Dr. D, and what

better drug combo: there's by far the most experience with IM and IFN, plus

we know that they work in entirely different ways - which is always a plus

when you're dealing with combinations.

My one reservation, which may be outmoded, is that so many patients on both

drugs at once seemed to bottom out with their blood counts. I know you can

support the marrow with white and red cell growth factors (not so with

platelets, because platelet growth factor is considered too toxic); however,

it concerns me a little that the combination DOES seem so marrow

suppressive. It would be OK if this is just because the body's own growth

factors are being switched off, but do we know that the combo is not

outright toxic to the marrow? And if it is, are we pretty sure the toxicity

isn't lasting in some way? The answers to this may be known, but I sure

don't know them!

As to whether I'd enter this trial, I might, but not that enthusiastically.

IFN didn't make me as sick as it did some folks, but the cumulative side

effects wore me down in the end and I'd hate to evoke them once again. I'm

not a candidate anyway though because a) I'm way farther out than 6 months

from dx, and I'm already PCRU!

Cheers,

> Date: Sun, 24 Apr 2005 16:03:47 -0400

> From: " Cheryl-Anne Simoneau " <cheryl.simoneau@...>

> Subject: I would like to discuss a study option

>

> Hello All,

>

> I noticed the clinical trial information posted below on the Asian List and

> I would like to have some discussion about it.

>

> The trial is being conducted by Dr. B. Druker and it involves combining IFN

> and IM. The interesting part is that depending on the response, IFN is

> dropped after the first year and if a molecular remission is achieved and

> held (PCRU) for two years based on bone marrow testing, IM is also dropped.

> Obviously this is quite appealing to me, as I tolerated IFN so well. The

> thought of a clinical trial being designed to reach an " end point " of no

> further medications is incredibly exciting; particularly so because Dr. D.

> is the PI.

>

> So, below is the information on the trial. My questions are:

>

> If you could enroll in this trial, would you?

>

> Is there anyone among us who is on this trial?

>

> What are any drawbacks that someone should think about with regards to this

> trial?

>

> Any general comments and your kind insight would be most helpful to me.

>

> Warm wishes to everyone,

> Cheryl-Anne

>

> Imatinib Mesylate and Interferon Alfa in Treating Patients With

> Chronic Myelogenous Leukemia

>

> This study is currently recruiting patients.

>

> Sponsors and Collaborators: Oregon Health and Science University

> National Cancer Institute (NCI)

> Information provided by: National Cancer Institute (NCI)

>

> Purpose

>

> RATIONALE: Imatinib mesylate and interferon alfa may interfere with

> the growth of the cancer cells. Combining imatinib mesylate with

> interferon alfa may kill more cancer cells.

>

> PURPOSE: Phase II trial to study the effectiveness of combining

> imatinib mesylate with interferon alfa in treating patients who have

> chronic myelogenous leukemia.

>

> Study Type: Interventional

> Study Design: Treatment

>

> Official Title: Phase II Study of Imatinib Mesylate and Interferon

> alfa in Patients With Chronic Phase Chronic Myelogenous Leukemia

>

> Further Study Details:

>

> OBJECTIVES:

>

> Determine the maximum tolerated dose of interferon alfa administered with

> imatinib mesylate in patients with chronic phase chronic myelogenous leukemia.

> (Phase I closed to accrual as of 7/9/03.) Determine the safety and

> tolerability of this regimen in this patient population. Determine the

> complete, major, and minor cytogenetic response rates and complete hematologic

> response rate in patients after 6 and 12 months of treatment with this

> regimen. Determine the molecular response (reverse transcriptase-polymerase

> chain reaction for bcr-abl) rate in patients who have a complete cytogenetic

> response after 6 and 12 months of treatment with this regimen. Determine the

> pharmacokinetics of this regimen in these patients. OUTLINE: This is a

> dose-escalation, multicenter study.

>

> Patients receive oral imatinib mesylate once daily beginning on day 1

> and interferon alfa (IFN-A) subcutaneously once daily or 3 times

> weekly beginning on day 14. Courses repeat every 35 days for up to 1

> year in the absence of disease progression or unacceptable toxicity.