40 Participants Needed

ABL001 Combo Therapy for Leukemia

Recruiting at 5 trial locations
MR
Overseen ByMarlise R. Luskin, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Marlise R. Luskin
Must be taking: ABL001, Dasatinib, Prednisone
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

The trial requires that certain medications be stopped before starting the study. Specifically, any TKI therapy must be discontinued for 5 half-lives before starting the trial, and other chemotherapy must be stopped 2 weeks prior, except for certain exceptions like steroids. Additionally, medications that strongly affect certain liver enzymes should be stopped unless medically necessary, in which case a review with the study investigator is needed.

What data supports the effectiveness of the drug ABL001 Combo Therapy for Leukemia?

The drug dasatinib, a component of the ABL001 Combo Therapy, is effective in treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, especially in patients who are resistant or intolerant to other treatments like imatinib. Additionally, asciminib, another component, has shown favorable results in patients with chronic myeloid leukemia in clinical trials.12345

What safety data exists for ABL001 (Asciminib) and Dasatinib (Sprycel) in humans?

Asciminib has shown favorable safety in patients with chronic myeloid leukemia in clinical trials. Dasatinib, while effective, can cause side effects like myelosuppression (reduced bone marrow activity) and pleural effusions (fluid around the lungs), but dose optimization has helped reduce these issues.12346

What makes the ABL001 Combo Therapy for Leukemia unique?

The ABL001 Combo Therapy is unique because it combines ABL001 (asciminib), an allosteric inhibitor that targets a different site on the BCR-ABL1 protein than traditional drugs, with dasatinib and prednisone. This combination aims to overcome resistance seen with other treatments by using different mechanisms to inhibit the cancer-driving protein, potentially leading to more effective disease control.15789

What is the purpose of this trial?

This research study is evaluating a drug called ABL001 taken in combination with dasatinib (Sprycel®) and prednisone (a steroid) as a possible treatment for B-cell Acute Lymphoblastic Leukemia that is BCR-ABL positive (BCR-ABL+ B-ALL) or Chronic Myeloid Leukemia (CML) in lymphoid blast crisis. BCR-ABL+ B-ALL is also called Philadelphia chromosome positive Acute Lymphoblastic Leukemia (Ph+ ALL).It is expected that 40-65 people will take part in this research study.* ABL001* Dasatinib (Sprycel®)* Prednisone* Blinatumomab

Research Team

Member Detail - DF/HCC

Marlise R Luskin, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with BCR-ABL+ B-cell ALL or CML in lymphoid blast crisis, who are unsuitable for standard chemotherapy due to age, comorbidities, or relapse. Participants must have normal organ function and agree to use effective contraception. Excluded are those suitable for standard therapy, with certain mutations or recent treatments, active infections like hepatitis/HIV, significant heart/lung issues, gastrointestinal disorders affecting drug absorption.

Inclusion Criteria

I am 18-49, have not had intense chemo, and cannot handle it due to health issues.
I am over 18 and my disease did not respond to at least one round of intense chemotherapy.
My organs are functioning normally.
See 7 more

Exclusion Criteria

I have a history of high blood pressure in the lungs.
I have a stomach or intestine problem that affects how I absorb medicine.
I have liver disease.
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ABL001, Dasatinib, and Prednisone. Blinatumomab is introduced from cycle 2. Dose escalation follows a 3+3 scheme to determine the recommended phase 2 dose.

6 cycles of 42 days each
Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • ABL001
  • Dasatinib
  • Prednisone
Trial Overview The trial is testing ABL001 combined with dasatinib (Sprycel®) and prednisone as a treatment option for Philadelphia chromosome positive Acute Lymphoblastic Leukemia (Ph+ ALL) and Chronic Myeloid Leukemia (CML) in blast crisis phase. The study aims to enroll 25-40 people to assess the effectiveness of this drug combination.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: ABL001, Dasatinib, Prednisone, BlinatumomabExperimental Treatment4 Interventions
- Dose escalation will occur conventional Fibonocci 3+3 dose escalation scheme to determine a recommended phase 2 dose (RP2D) * Dasatinib-Fixed doses oral once a day per cycle * ABL001 is administered orally daily per cycle * Prednisone-Fixed doses oral once a day per cycle. --- Prednisone will be tapered and stop during cycle 2. * Blinatumomab - intravenous continuous infusion beginning no earlier than cycle 2 day 1 * Blinatumomab - Day 1-28 of each 42-day cycle, cycles 2-6, total of 5 cycles

ABL001 is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Scemblix for:
  • Chronic myeloid leukemia (CML) in patients with a resistance or intolerance to two or more tyrosine kinase inhibitors
🇪🇺
Approved in European Union as Scemblix for:
  • Chronic myeloid leukemia (CML) in patients with a resistance or intolerance to two or more tyrosine kinase inhibitors

Find a Clinic Near You

Who Is Running the Clinical Trial?

Marlise R. Luskin

Lead Sponsor

Trials
1
Recruited
40+

Marlise Luskin, MD

Lead Sponsor

Trials
1
Recruited
40+

Novartis

Industry Sponsor

Trials
1,646
Recruited
2,778,000+
Vasant Narasimhan profile image

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye profile image

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Findings from Research

Dasatinib, a multiple kinase inhibitor, is rapidly absorbed in the body after oral administration, with a peak concentration reached in about 30 minutes and a short elimination half-life of less than 4 hours, indicating efficient absorption and metabolism.
Most of dasatinib is eliminated through feces (85%), and while several metabolites are formed, they are not expected to significantly contribute to the drug's therapeutic effects, as the active metabolites do not show strong inhibitory activity against key kinases.
Metabolism and disposition of dasatinib after oral administration to humans.Christopher, LJ., Cui, D., Wu, C., et al.[2015]
A clinical study involving 56 volunteers demonstrated that the generic dasatinib tablet (YiNiShu®) is bioequivalent to the branded version (Sprycel®) under both fasting and fed conditions, indicating similar pharmacokinetic profiles.
Both dasatinib formulations showed a good safety profile, confirming that patients can expect comparable efficacy and safety when using either version of the medication.
Pharmacokinetics and safety of dasatinib and its generic: a phase I bioequivalence study in healthy Chinese subjects.Wang, Y., Xue, J., Su, Z., et al.[2023]
Dasatinib, approved by the FDA for treating chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL), showed a major cytogenetic response rate of 45% in chronic phase CML and significant hematologic response rates in other phases of CML and Ph(+) ALL, indicating its efficacy in patients resistant to prior therapies.
The treatment was associated with common side effects such as myelosuppression, bleeding, and fluid retention, highlighting the importance of monitoring patient safety during dasatinib therapy.
Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate.Brave, M., Goodman, V., Kaminskas, E., et al.[2023]

References

Metabolism and disposition of dasatinib after oral administration to humans. [2015]
Pharmacokinetics and safety of dasatinib and its generic: a phase I bioequivalence study in healthy Chinese subjects. [2023]
Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate. [2023]
Asciminib monotherapy for newly diagnosed chronic myeloid leukemia in chronic phase: the ASC4FIRST phase III trial. [2023]
Dasatinib: A Review in Chronic Myeloid Leukaemia and Ph+ Acute Lymphoblastic Leukaemia. [2022]
[Guidelines for the management of dasatinib (Sprycel)-induced side effects in chronic myelogenous leukemia and Philadelphia positive acute lymphoblastic leukemias]. [2015]
New strategies for the first-line treatment of chronic myeloid leukemia: can resistance be avoided? [2009]
The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. [2022]
Combined Abl inhibitor therapy for minimizing drug resistance in chronic myeloid leukemia: Src/Abl inhibitors are compatible with imatinib. [2015]
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