Veliparib + Topotecan ± Carboplatin for Leukemia

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antiretrovirals, ABT-888

Disqualifiers: CNS leukemia, Seizure disorder, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28-63 days per course, up to 6 courses

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining veliparib, topotecan hydrochloride, and carboplatin to treat aggressive blood cancers, such as relapsed or hard-to-treat leukemia or myeloproliferative disorders. Veliparib targets specific enzymes to stop cancer cell growth, while topotecan and carboplatin are chemotherapy drugs that kill cancer cells or prevent their division. The study primarily aims to determine the safest and most effective dose of these combined drugs. Suitable participants include those whose blood cancer has returned or not responded to initial treatment and who experience conditions like increasing spleen or liver size or new symptoms such as fever or weight loss. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

The trial requires that you stop any current chemotherapy, radiotherapy, or immunotherapy before joining. You also need to stop certain medications like hydroxyurea, steroids, and others at least 24 hours before starting the trial. However, the protocol does not specify all medications, so it's best to discuss your specific situation with the trial team.

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

Research has shown that combining veliparib with topotecan and carboplatin is undergoing careful testing to ensure safety. In some studies, patients responded well to this combination, indicating a noticeable effect on their cancer.

Since this is an early trial phase, the main focus remains on identifying the safest dose and understanding the side effects. Common side effects reported with these drugs include nausea, tiredness, and low blood cell counts. These side effects are typical in cancer treatments and are under close observation.

Overall, while the combination appears promising, researchers continue to study its safety and evaluate side effects to ensure it is well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Veliparib in combination with Topotecan and Carboplatin for leukemia because it introduces a new way to attack cancer cells. Veliparib is a PARP inhibitor, which means it blocks an enzyme cancer cells use to repair their DNA, making them more vulnerable to treatment. This is different from the standard chemotherapy drugs that primarily aim to kill rapidly dividing cells. By targeting DNA repair, this combination could potentially enhance the effectiveness of existing drugs like Topotecan and Carboplatin, offering a promising new avenue for tackling leukemia more effectively.

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

Research has shown that combining veliparib with topotecan and carboplatin may help treat certain blood cancers, such as leukemia. In this trial, participants will receive a combination of veliparib and topotecan, with some also receiving carboplatin. One study found that about one-third of patients experienced their cancer shrinking or disappearing with this combination. Veliparib blocks enzymes that cancer cells need to grow, while topotecan and carboplatin help kill cancer cells or stop them from multiplying. These early results suggest this drug combination could be effective, but further research is needed to confirm these findings. ^{1 2 6 7 8}

Who Is on the Research Team?

Keith W Pratz

Principal Investigator

Johns Hopkins University/Sidney Kimmel Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with certain blood cancers like acute leukemia, high-risk myelodysplasia, or aggressive myeloproliferative disorders who have relapsed or didn't respond to previous treatments. Participants must be physically stable enough to consent and follow the protocol, not have had more than three prior chemotherapy regimens, and should not be pregnant or breastfeeding. They must use effective contraception during the study.

Inclusion Criteria

I have waited the required time since my last cancer treatment.

My brain leukemia has been stable for over 3 months after treatment.

I have chronic myelomonocytic leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive veliparib orally twice daily on days 1-8, 1-14, or 1-21 and topotecan hydrochloride with or without carboplatin IV continuously over 120 hours on days 3-7. Treatment repeats every 28-63 days for up to 6 courses.

28-63 days per course, up to 6 courses

Pharmacokinetic Studies

Patients undergo blood sample collection periodically for pharmacokinetic studies.

Throughout treatment phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Topotecan Hydrochloride
• Veliparib

Trial Overview The trial is testing how well veliparib works alongside topotecan hydrochloride with or without carboplatin in treating specific blood cancers. Veliparib blocks enzymes that cancer cells need to grow while the other drugs aim to kill cancer cells by stopping their division.

How Is the Trial Designed?

Group I: Treatment (veliparib, topotecan hydrochloride, carboplatin) Experimental Treatment 4 Interventions

Patients receive veliparib orally twice daily on days 1-8, 1-14, or 1-21 and topotecan hydrochloride with or without carboplatin IV continuously over 120 hours on days 3-7. Treatment repeats every 28-63 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5315611/

A Phase I study of topotecan, carboplatin and the PARP ... This study evaluated veliparib incorporation into leukemia induction therapy using a previously described topotecan/carboplatin backbone.

2. aacrjournals.org aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-16-1274/352114/p/A-Phase-I-Study-of-Topotecan-Carboplatin-and-the

A Phase I Study of Topotecan, Carboplatin and the PARP ... Results: A total of 99 patients received veliparib 10–100 mg orally twice daily on days 1–8, 1–14, or 1–21 along with continuous infusion topotecan 1.0–1.2 mg/m ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00588991

Veliparib and Topotecan With or Without Carboplatin in ... This phase I trial is studying the side effects and best dose of veliparib when given together with topotecan hydrochloride with or without carboplatin in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5837045/

Exposure-Response of Veliparib to Inform Phase II Trial ... A phase I trial of veliparib in combination with topotecan plus carboplatin (T+C) demonstrated 33% objective response rate in patients with ...

5. researchgate.net researchgate.net/figure/Summary-of-clinical-responses-to-veliparib-in-combination-with-topotecan-and-carboplatin_tbl2_306435090

Summary of clinical responses to veliparib in combination ... This study evaluated veliparib incorporation into leukemia induction therapy using a previously described topotecan/carboplatin backbone. Experimental ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/23/4/899/122880/A-Phase-I-Study-of-Topotecan-Carboplatin-and-the

A Phase I Study of Topotecan, Carboplatin and the PARP ... A single 80-mg dose of veliparib, as well as veliparib in combination with topotecan + carboplatin, induced DNA damage as manifested by histone H2AX ...

7. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.13253

Population pharmacokinetics and site of action exposures of ... Efficacy and safety data from Phase I and II trials demonstrated that PARP inhibitors such as olaparib and veliparib in combination with ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27551000/

A Phase I Study of Topotecan, Carboplatin and the ... - PubMed This study evaluated veliparib incorporation into leukemia induction therapy using a previously described topotecan/carboplatin backbone.