Capivasertib for Leukemia

(CAVALRY Trial)

Overseen By Clinical Trials Intake

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Chicago

Must not be taking: Strong CYP3A inducers

Disqualifiers: Ph-positive ALL, Burkitt's, uncontrolled infection, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, capivasertib, for individuals with certain types of relapsed or hard-to-treat leukemia or lymphoma. The researchers aim to find the best dose when combined with standard treatments. The goal is to determine if adding capivasertib to usual chemotherapy and a drug called venetoclax is safe and effective. Suitable candidates have specific types of leukemia or lymphoma that have returned or did not respond to treatment, with noticeable signs in their blood or bone marrow. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

Research shows that capivasertib is being tested for safety when combined with treatments like venetoclax and chemotherapy. In previous studies, common side effects of capivasertib included diarrhea and rash. Most participants managed these side effects, though a few stopped treatment due to them, which was rare.

Currently, researchers are testing capivasertib at different doses to find the safest option. They are still learning how well it works with other drugs for leukemia. As the trial is in its early stages, complete safety details are still being determined.

For those considering joining a clinical trial, it's important to know that some side effects might occur, but researchers are working to find the safest way to use this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for leukemia?

Researchers are excited about capivasertib for leukemia because it works differently from most standard treatments. While typical therapies for leukemia often focus on targeting specific cancer cells directly, capivasertib is a targeted therapy that inhibits a protein called AKT, which is involved in cell growth and survival. This mechanism could potentially disrupt the cancer cells' ability to thrive, offering a new avenue for treatment. Additionally, when combined with venetoclax and the mini-hyperCVD chemotherapy regimen, capivasertib could enhance the effectiveness of these existing therapies, providing a more robust approach to treatment.

What evidence suggests that capivasertib might be an effective treatment for leukemia?

Research has shown that capivasertib, a type of drug, holds promise when combined with other treatments. In this trial, participants will receive various combinations of capivasertib, venetoclax, and mini-hyperCVD chemotherapy. Studies have found that combining capivasertib with venetoclax provides significant benefits in models of a certain type of lymphoma. Another study showed that capivasertib, when used with other drugs, helped some cancer patients live twice as long compared to those who didn't receive it. These findings suggest that capivasertib could effectively treat leukemia when used with venetoclax and chemotherapy. This combination works by blocking specific pathways that cancer cells need to grow. ^{1 2 6 7 8}

Who Is on the Research Team?

Caner Saygin

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for individuals with specific types of leukemia or lymphoma. Participants should be able to undergo a standard chemotherapy regimen and have not had certain treatments that might interfere with the study drugs. The full list of eligibility criteria will determine who can join.

Inclusion Criteria

Previously untreated patients with acute leukemia with lymphoid lineage (B-ALL, T-ALL, ETP-ALL, mixed phenotype or bi-phenotypic) or lymphoblastic lymphoma (B- or T-lineage) with bone marrow or peripheral blood involvement with ≥20% leukemic blasts. Patients with isolated extramedullary disease that is measurable by CT scan are also eligible. Previous therapy with dexamethasone or hydroxyurea given for cytoreductive purposes is allowed. Must be 40 years old or older with ECOG performance status 0-2. Must have adequate organ function per protocol criteria. Must be at least 2 weeks from major surgery. Must voluntarily sign and date an informed consent prior to the initiation of any screening or study-specific procedures. Females of childbearing potential will use effective contraception during protocol treatment and for at least 8 months after the last dose. Males with female partners of reproductive potential will use effective contraception during protocol treatment and for at least 5 months after the last dose.

COHORT 2: Relapsed or refractory patients with acute leukemia with lymphoid lineage (B-ALL, T-ALL, ETP-ALL, mixed phenotype or bi-phenotypic) or lymphoblastic lymphoma (B- or T-lineage) with bone marrow or peripheral blood involvement with ≥5% leukemic blasts. Patients with isolated extramedullary disease that is measurable by CT scan are also eligible. Must be 18 years or older with ECOG performance status 0-2. Must have adequate organ function meeting protocol criteria. Must be at least 2 weeks from major surgery or radiation therapy. Must have recovered from clinically significant toxicities related to prior treatments. Must voluntarily sign and date an informed consent prior to the initiation of any screening or study-specific procedures. Females of childbearing potential will use effective contraception during protocol treatment and for at least 8 months after the last dose. Males with female partners of reproductive potential will use effective contraception during protocol treatment and for at least 5 months after the last dose.

COHORT 1: Patients with acute leukemia with lymphoid lineage (B-ALL, T-ALL, ETP-ALL, mixed phenotype or bi-phenotypic) or lymphoblastic lymphoma (B- or T-lineage) that is relapsed or refractory, with bone marrow or peripheral blood involvement with ≥5% leukemic blasts. Patients with isolated extramedullary disease that is measurable by CT scan are also eligible. Must be 18 years or older with ECOG performance status 0-2. Must have adequate organ function meeting protocol criteria. Must be at least 2 weeks from major surgery or radiation therapy. Must have recovered from clinically significant toxicities related to prior treatments. Must voluntarily sign and date an informed consent prior to the initiation of any screening or study-specific procedures. Females of childbearing potential will use effective contraception during protocol treatment and for at least 8 months after the last dose. Males with female partners of reproductive potential will use effective contraception during protocol treatment and for at least 5 months after the last dose.

Exclusion Criteria

Patient is pregnant or breastfeeding

I do not have active hepatitis B or C, and if I have HIV, it is under control.

Other severe acute, chronic medical, psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the treating physician, would make the patient inappropriate for entry into this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Determine the recommended dose of capivasertib that can be safely given with venetoclax and chemotherapy. Several doses of capivasertib may be tested in small groups of subjects.

8 weeks

Multiple visits for dose adjustment and monitoring

Expansion

Treat additional participants with the recommended safe dose of capivasertib to learn more about the safety of giving these drugs together.

8 months

Randomized Treatment

Participants are randomized to receive mini-hyperCVD and venetoclax alone or with capivasertib.

8 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Capivasertib

Trial Overview

The trial is testing the safety of adding Capivasertib to a standard leukemia treatment (mini-hyperCVD) combined with Venetoclax. It's divided into three parts: finding a safe dose, further safety evaluation, and then comparing it with the standard treatment in randomized groups.

How Is the Trial Designed?

Group I: Cohort 3 -- Arm 2 -- mini-hyperCVD + venetoclax + capivasertib (Randomized) Experimental Treatment 6 Interventions

Participants randomized to this arm will receive mini-hyperCVD + venetoclax and capivasertib.

Group II: Cohort 2 (Expansion) Experimental Treatment 6 Interventions

In this arm, the best, safe dose of capivasertib found after completion of enrollment to dose escalation (cohort 1) arms, will be tested in combination with venetoclax and mini-hyperCVD chemotherapy regimen.

Group III: Cohort 1 - Dose Escalation (Dose Level 2) Experimental Treatment 6 Interventions

In this arm, a dose of 400 mg dose of capivasertib will be tested in combination with venetoclax and mini-hyperCVD chemotherapy regimen.

Group IV: Cohort 1 - Dose Escalation (Dose Level 1) Experimental Treatment 6 Interventions

In this arm, a dose of 320 mg dose of capivasertib will be tested in combination with venetoclax and mini-hyperCVD chemotherapy regimen.

Group V: Cohort 1 - Dose Escalation (Dose Level -1) Experimental Treatment 6 Interventions

In this arm, a dose of 200 mg dose of capivasertib will be tested in combination with venetoclax and mini-hyperCVD chemotherapy regimen.

Group VI: Cohort 3 -- Arm 1 -- mini-hyperCVD + venetoclax (Randomized) Active Control 5 Interventions

Participants randomized to this arm will receive mini-hyperCVD + venetoclax.

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Citations

1.

aacrjournals.org

aacrjournals.org/cancerres/article/85/8_Supplement_1/3951/758422/Abstract-3951-AKT-inhibitor-capivasertib-combines

Abstract 3951: AKT inhibitor capivasertib combines with ...

Using a clinically relevant dose and schedule of capivasertib, treatment combination groups led to 60% and 70% TGI in the MOLT4 and Karpas-231 ...

2.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK612198/

Clinical Review - Capivasertib (Truqap) - NCBI Bookshelf - NIH

Median OS was 39.0 months (95% CI, 22.3 months to 50.7 months) in the group receiving capivasertib plus fulvestrant versus 20.9 months (95% CI, 14.1 months to ...

3.

nature.com

nature.com/articles/s41375-024-02401-9

Potent combination benefit of the AKT inhibitor capivasertib ...

The AKT inhibitor, capivasertib, in combination with the BCL-2 inhibitor, venetoclax, produced notable therapeutic benefit in preclinical models of DLBCL.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07175415

Study Details | NCT07175415 | HEM-iSMART E: ...

Sub-protocol E is a phase I/II trial evaluating the safety and efficacy of capivasertib + venetocolax in combination with dexamethasone in ...

5.

jmcp.org

jmcp.org/doi/10.18553/jmcp.2025.31.9.900

Capivasertib cost-effectiveness in treating advanced breast ...

The results of our PSA indicated that there was a low likelihood of Capivasertib being cost-effective when compared with standard treatment at ...

6.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e13101

Single center study of efficacy and safety of capivasertib in ...

At capivasertib initiation, 85.3% had bone metastases, 76.5% had visceral disease, and 17.6% had brain metastases. Median number of prior ...

7.

esmoopen.com

esmoopen.com/article/S2059-7029(25)00806-3/fulltext

366P Efficacy and safety of capivasertib in HR+/HER2

Capivasertib significantly improved progression-free survival (PFS: HR = 0.61, 95% CI: 0.48–0.77, p = 0.0124, I2 = 15.8%) and overall survival (OS: HR = 0.68, ...

8.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2214131

Capivasertib in Hormone Receptor–Positive Advanced ...

The safety profile showed that diarrhea and rash were the most common adverse events, and the incidence of discontinuation due to adverse events ...