Topotecan + Carboplatin + Veliparib for Leukemia

Not currently recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: Active CNS disease, Uncontrolled infection, 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: Unknown

Duration: 4-9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a drug combination—topotecan and carboplatin, with or without veliparib—in treating blood cancers such as advanced myeloproliferative disorders and certain leukemias. The goal is to determine if adding veliparib, which may block cancer cell growth, improves outcomes compared to using only topotecan and carboplatin. The trial is open to individuals with certain blood cancers that have spread or are difficult to control and have had limited prior treatments. Participants will join one of two groups: one receiving all three drugs and the other receiving only topotecan and carboplatin. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial does not specify if you need to stop taking your current medications, but you must stop any chemotherapy or radiotherapy at least 4 weeks before starting, except for hydroxyurea. You can continue tyrosine kinase inhibitors until 24 hours before the trial starts.

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

Research shows that the combination of veliparib, topotecan, and carboplatin has undergone safety testing in people. One study on this combination found it was generally well-tolerated, with about 33% of patients responding positively. Some side effects have been reported, but medical care can usually manage them.

Topotecan and carboplatin have been studied before for treating leukemia. They can cause low blood cell counts, increasing the risk of infections. These effects are known and manageable in a clinical setting.

This current study focuses on safety, indicating that the treatment has shown some safety in earlier studies but requires further evaluation. Researchers will closely monitor participants for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for leukemia because they involve a novel combination of drugs, including veliparib, which is not typically used in current treatments. Veliparib is a PARP inhibitor, offering a unique mechanism that targets the DNA repair pathways in cancer cells, potentially increasing the effectiveness of chemotherapy. Additionally, combining veliparib with carboplatin and topotecan might enhance the overall therapeutic effect and offer new hope for patients who haven't responded well to standard options like cytarabine and daunorubicin. This combination approach could potentially improve treatment outcomes and expand the arsenal against leukemia.

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

Research has shown that combining veliparib with topotecan and carboplatin might enhance treatment effectiveness for certain types of leukemia. In this trial, participants in Arm A will receive veliparib, topotecan, and carboplatin. Veliparib blocks specific enzymes that cancer cells need to grow. Studies have found that adding veliparib can kill more cancer cells than using topotecan and carboplatin alone, which is the treatment for participants in Arm B. This combination might better stop cancer cells from growing and spreading. Early results are promising, suggesting this could be a more effective option for treating advanced blood disorders that are difficult to manage. ^{4 6 7 8 9}

Who Is on the Research Team?

Keith W Pratz

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with advanced myeloproliferative disorders or certain types of leukemia (AML, CMML) who haven't had more than two prior chemo treatments. They should be in decent physical shape and have normal organ function. Pregnant women can't join, and participants must agree to use birth control.

Inclusion Criteria

Agreement to use adequate contraception by women of child-bearing potential and men

I am mostly self-sufficient and can carry out daily activities.

I have been recently diagnosed with AML following a blood disorder.

Exclusion Criteria

I haven't had chemotherapy or radiotherapy in the last 4 weeks.

I do not have any unmanaged ongoing illnesses.

Human immunodeficiency virus (HIV) patients with specific criteria

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive topotecan hydrochloride and carboplatin with or without veliparib for up to 4 cycles

4-9 months

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Topotecan
• Topotecan Hydrochloride
• Veliparib

Trial Overview The study tests how well a combination of chemotherapy drugs (topotecan hydrochloride and carboplatin) works with or without an additional drug called veliparib in treating advanced blood cancers. It's looking at whether adding veliparib improves treatment outcomes.

How Is the Trial Designed?

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

Patients receive veliparib PO BID on days 1-21 and topotecan hydrochloride IV continuously over 24 hours and carboplatin IV continuously over 24 hours on days 3-7. Treatment repeats every 28-63 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (topotecan hydrochloride, carboplatin) Active Control 3 Interventions

Patients receive topotecan hydrochloride IV continuously over 24 hours and carboplatin IV continuously over 24 hours on days 1-5. Treatment repeats every 28-63 days for up to 4 cycles 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+

Published Research Related to This Trial

Topotecan, a drug that targets topoisomerase I, has shown significant antitumor activity when combined with various chemotherapy agents like cisplatin and doxorubicin in both adult and pediatric patients with solid tumors.

The main side effect of these combination therapies is myelosuppression, particularly neutropenia, which limits the dosage; however, many early studies have reported major responses, indicating the potential effectiveness of these regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan in combination chemotherapy. Rowinsky, EK., Kaufmann, SH.[2017]

In a phase II trial involving 120 patients with extensive-stage small cell lung cancer, the combination of paclitaxel, carboplatin, and etoposide showed a significantly higher overall response rate of 78% compared to 48% for the paclitaxel and topotecan combination.

The paclitaxel-carboplatin-etoposide regimen also resulted in a longer median time to progression (7.6 months) compared to the paclitaxel-topotecan group (5.5 months), indicating it may be a more effective initial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin/etoposide versus paclitaxel/topotecan for extensive-stage small cell lung cancer: a Minnie Pearl Cancer Research Network randomized, prospective phase II trial. Greco, FA., Thompson, DS., Morrissey, LH., et al.[2015]

Citations

1. 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.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00588991

Veliparib and Topotecan With or Without Carboplatin in ... Giving veliparib together with topotecan hydrochloride and carboplatin may kill more cancer cells. Detailed Description. PRIMARY OBJECTIVES: I. To determine ...

3. 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.

4. 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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03289910

Study Details | NCT03289910 | Topotecan Hydrochloride ... Giving topotecan hydrochloride, carboplatin, and veliparib may work better in treating patients with myeloproliferative disorders and acute myeloid leukemia or ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9425957/

Topotecan in combination chemotherapy The safety and efficacy of combination chemotherapy regimens containing topotecan ... carboplatin also have been studied in patients with refractory leukemia.

7. cancernetwork.com cancernetwork.com/view/topotecan-active-first-line-combination-therapy-advanced-non-small-cell-lung-cancer

Topotecan Active as First-Line Combination Therapy for ... In thisstudy, the median survival was 35.4 weeks. The most common adverse eventsincluded grade 3/4 neutropenia, anemia, and thrombocytopenia in 70%, 48%, and46% ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00003255

Carboplatin Plus Topotecan in Treating Patients With ... PURPOSE: Phase II trial to study the effectiveness of combining carboplatin and topotecan in treating patients with relapsed acute myelogenous ...

9. ema.europa.eu ema.europa.eu/en/documents/product-information/hycamtin-epar-product-information_en.pdf

Hycamtin, INN-Topotecan - EMA Topotecan monotherapy and topotecan in combination with cisplatin are commonly associated with clinically relevant thrombocytopenia. This should be taken into ...