Imatinib or Dasatinib for Chronic Myeloid Leukemia

Not currently recruiting at 386 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Pregnancy, Major surgery, Cardiac symptoms, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, imatinib mesylate and dasatinib, to evaluate their effectiveness for individuals with newly diagnosed chronic myeloid leukemia (CML). Researchers aim to determine if these drugs can halt cancer cell growth by blocking essential enzymes. Participants will be randomly assigned to receive either imatinib once or twice daily, or dasatinib twice daily, with treatment lasting up to five years. Individuals diagnosed with CML within the last six months who have not received treatments other than hydroxyurea or anagrelide may be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you must not have received prior treatment for CML, except for hydroxyurea and/or anagrelide. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both imatinib mesylate and dasatinib are generally well-tolerated treatments for chronic myeloid leukemia. Imatinib has achieved a high survival rate in real-world settings, with 95% of patients surviving at least three years and 93% not experiencing disease progression. These outcomes suggest it is a safe and effective option.

Dasatinib also maintains a strong safety record. Studies have demonstrated its quick action and safety for up to five years. However, about 20% of patients experienced side effects that required stopping the treatment. Despite this, dasatinib has been effective for many, with 82% of patients surviving at least four years.

Both treatments have been used successfully, but like any medication, they can have side effects. Discussing these with the trial team is important to understand their implications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for chronic myeloid leukemia (CML) because they offer targeted approaches with specific benefits. Unlike the standard of care, which often revolves around tyrosine kinase inhibitors like imatinib, dasatinib presents a unique mechanism by targeting additional pathways, potentially overcoming resistance in some patients. Imatinib mesylate is explored in different dosing schedules—either once or twice daily—which might optimize its effectiveness and minimize side effects for individuals. These variations aim to provide more personalized treatment options, possibly leading to better outcomes for CML patients.

What evidence suggests that this trial's treatments could be effective for chronic myeloid leukemia?

This trial will compare the effectiveness of Imatinib Mesylate and Dasatinib in treating chronic myeloid leukemia (CML). Research has shown that Imatinib Mesylate, which participants in this trial may receive, is highly effective for CML. Studies found that 97.8% of patients who responded well to this treatment were still alive after 10 years, with up to 95% living at least three years after starting the therapy.

Dasatinib, another treatment option in this trial, has shown promising results. About 77% of patients reached an important treatment goal within a year, and in the long term, 82% were still alive four years after starting dasatinib. Both treatments block certain enzymes that help cancer cells grow, making them strong options for managing CML. ^{3 5 6 7 8}

Who Is on the Research Team?

Brian J Druker

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed chronic phase chronic myelogenous leukemia who haven't had treatment except possibly hydroxyurea or anagrelide. They should be in good physical condition, not pregnant or breastfeeding, and willing to use birth control. Major surgery must not have been done recently, and they shouldn't have serious bleeding disorders or certain heart conditions.

Inclusion Criteria

At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base

Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamate pyruvate transaminase (SGPT)/alanine transaminase (ALT) =< 2.0 x the IULN

All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

Exclusion Criteria

Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method

I haven't had major surgery in the last 28 days and have recovered from past surgeries.

I have no cancer history except for certain skin cancers, early-stage cancers in remission, or any cancer I've been free from for 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive imatinib mesylate or dasatinib. Treatment repeats every 4 weeks for up to 5 years in the absence of disease progression or unacceptable toxicity.

5 years

Monthly visits for the first year, then every 6 months for years 2 and 3, and annually for years 4 and 5

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

15 years

Annually

What Are the Treatments Tested in This Trial?

Interventions

• Dasatinib
• Imatinib Mesylate

Trial Overview The study compares the effectiveness of two drugs: Imatinib Mesylate at different doses and Dasatinib. These medications are designed to block enzymes that cancer cells need to grow. The trial randomly assigns patients to receive one of these treatments.

How Is the Trial Designed?

Group I: Arm III (dasatinib) Experimental Treatment 2 Interventions

Patients receive dasatinib PO BID. Treatment repeats every 4 weeks for up to 5 years in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (BID imatinib mesylate) Experimental Treatment 2 Interventions

Patients receive imatinib mesylate PO BID. Treatment repeats every 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity.

Group III: Arm I (QD imatinib mesylate) Experimental Treatment 2 Interventions

Patients receive imatinib mesylate PO QD. Treatment repeats every 4 weeks for up to 5 years in the absence of disease progression or unacceptable toxicity.

Dasatinib is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Sprycel for:

• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)

Approved in European Union as Sprycel for:

• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)

Approved in Canada as Sprycel for:

• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Dasatinib demonstrated a higher rate of major molecular response (MMR) at 18 months compared to imatinib (76% vs 37%), indicating it may be more effective in achieving deeper responses in newly diagnosed chronic phase chronic myeloid leukemia (CML-CP) patients.

Both dasatinib and imatinib were well-tolerated with mostly mild side effects, but dasatinib was associated with specific adverse events like pleural effusion and thrombocytopenia, while imatinib had more cases of hypophosphatemia and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preliminary comparison of efficacy and safety of dasatinib and imatinib in newly diagnosed chronic myeloid leukemia]. Zhou, L., Wang, JX., Huang, XJ., et al.[2022]

In a study of 117 patients with chronic myeloid leukemia, dasatinib showed higher adherence to treatment (91%) compared to nilotinib (82%) over two years.

Both dasatinib and nilotinib demonstrated similar efficacy in terms of progression-free survival (PFS) at 92%, indicating that while dasatinib may be better adhered to, both drugs are equally effective in preventing disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence, persistence and efficacy of dasatinib and nilotinib in the treatment of patients resistant or intolerant to imatinib with chronic myeloid leukemia in chronic phase: an Italian multicenter study over two years in real life. Santoleri, F., Ranucci, E., La Barba, G., et al.[2022]

In a study of 519 patients with newly diagnosed chronic-phase CML, dasatinib resulted in a higher rate of complete cytogenetic response at 12 months compared to imatinib (77% vs. 66%), indicating its greater efficacy as a first-line treatment.

Dasatinib not only achieved higher response rates but also did so more quickly than imatinib, with a major molecular response rate of 46% compared to 28%, suggesting that dasatinib may lead to better long-term outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. Kantarjian, H., Shah, NP., Hochhaus, A., et al.[2023]

In a study of 253 patients with newly diagnosed chronic-phase chronic myeloid leukemia, dasatinib (DAS) showed a higher complete cytogenetic remission rate (84%) compared to imatinib (IM) (69%), indicating DAS may be more effective in achieving initial treatment goals.

While DAS resulted in more complete cytogenetic and deeper molecular responses after 12 months, both treatments had similar overall and progression-free survival rates, with DAS associated with higher rates of hematologic toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of dasatinib 100 mg versus imatinib 400 mg in newly diagnosed chronic-phase chronic myeloid leukemia. Radich, JP., Kopecky, KJ., Appelbaum, FR., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10388268/

Insights into dasatinib use and outcomes in real-world ... Over 30% of patients failed to achieve deep molecular response (DMR) and 20% experienced adverse drug reactions (ADR) necessitating treatment discontinuation ...

2. sprycel-hcp.com sprycel-hcp.com/efficacy-newly-diagnosed

SPRYCEL® (dasatinib) Efficacy - Newly Diagnosed Patients 77% of SPRYCEL patients achieved the cCCyR 12-month treatment milestone. 83% achieved the Year 5 treatment milestone.1. IMPORTANT INFORMATION ABOUT ADVERSE ...

3. news.bms.com news.bms.com/news/details/2010/Four-Year-Follow-Up-Data-for-SPRYCEL-dasatinib-Demonstrate-82-Percent-Overall-Survival-in-Patients-with-Chronic-Myeloid-Leukemia-Who-Failed-Gleevec1/default.aspx

Four-Year Follow-Up Data for SPRYCEL® (dasatinib) ... At four years, for all patients administered SPRYCEL 100 mg once daily, overall survival was 82% (95% CI: 76%-88%) and progression-free survival was 66% (95% ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6614/528020/Real-World-Data-of-Molecular-Response-Using

Real-World Data of Molecular Response Using Different ... After 3 months of therapy, CHR was achieved in overall 96% patients (98% with dasatinib 70 mg & 96% with dasatinib 100 mg dose). Early molecular ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025019883

CML-1199: Targeting Chronic Myeloid Leukemia: Meta ... Dasatinib was associated with a higherMMR rate at 12 months compared with high-dose imatinib (72.4% vs 60.8%; risk ratio [RR] 1.19, 95% CI 1.07–1.32; P = 0.002) ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31999839/

Long-term results of frontline dasatinib in chronic myeloid ... Conclusions: After this long-term follow-up, dasatinib continues to show an excellent safety profile and produces rapid cytogenetic responses ...

7. sprycel-hcp.com sprycel-hcp.com/safety-newly-diagnosed

SPRYCEL® (dasatinib) Safety Profile - Newly Diagnosed ... SPRYCEL had a well-established and consistent safety profile through Year 5 · 1618 adult patients with chronic phase CML was 29 months (range 0–92.9 months) · 324 ...

8. nature.com nature.com/articles/s41408-018-0122-3

Long-term efficacy and safety of dasatinib in patients with ... The best response of CHR at any time within 5 years was reached in 51% and 54% of patients in the QD and BID arms, respectively. Fig. 1: ...