Topotecan + Carboplatin + Veliparib for Leukemia

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

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies how well topotecan hydrochloride and carboplatin with or without veliparib work in treating patients with myeloproliferative disorders that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced), and acute myeloid leukemia or chronic myelomonocytic leukemia. Drugs used in chemotherapy, such as topotecan hydrochloride and carboplatin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Veliparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving topotecan hydrochloride, carboplatin, and veliparib may work better in treating patients with myeloproliferative disorders and acute myeloid leukemia or chronic myelomonocytic leukemia compared to topotecan hydrochloride and carboplatin alone.

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 the combination of Topotecan, Carboplatin, and Veliparib safe for humans?

The combination of Topotecan, Carboplatin, and Veliparib has been studied in patients with leukemia and other blood cancers. The main safety concern is mucositis (painful inflammation and ulceration of the mucous membranes lining the digestive tract), which was dose-limiting. Hematologic toxicity (blood-related side effects) such as neutropenia (low white blood cell count) and thrombocytopenia (low platelet count) were also observed, but these side effects can be managed with dose adjustments. ^{1 2 3 4 5}

What makes the drug combination of Topotecan, Carboplatin, and Veliparib unique for treating leukemia?

This drug combination is unique because it includes Veliparib, a PARP inhibitor that enhances the effectiveness of chemotherapy by delaying DNA repair, making cancer cells more susceptible to treatment. This approach is particularly promising for patients with aggressive forms of leukemia and those with specific DNA repair defects, offering a novel mechanism compared to standard treatments. ^{2 3 4 5 6}

What data supports the effectiveness of the drug combination Topotecan, Carboplatin, and Veliparib for treating leukemia?

Research shows that the combination of Topotecan, Carboplatin, and Veliparib has a 33% response rate in patients with certain blood cancers, with a higher response rate of 64% in patients with specific aggressive conditions. This suggests potential effectiveness, especially in patients with aggressive myeloproliferative neoplasms or related leukemias. ^{1 3 4 5 6}

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. United States pubmed.ncbi.nlm.nih.gov

Topotecan in combination chemotherapy. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

A Phase I Study of Topotecan, Carboplatin and the PARP Inhibitor Veliparib in Acute Leukemias, Aggressive Myeloproliferative Neoplasms, and Chronic Myelomonocytic Leukemia. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Exposure-Response of Veliparib to Inform Phase II Trial Design in Refractory or Relapsed Patients with Hematological Malignancies. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Nursing considerations for managing topotecan-related hematologic side effects. [2013]

5. England 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. [2015]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Preliminary results of combined therapy with topotecan and carboplatin in advanced non-small-cell lung cancer. [2017]