Combination Chemotherapy for Acute Lymphoblastic Leukemia

Recruiting in Palo Alto (17 mi)

Overseen by Maro Ohanian

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Peripheral neuropathy, Hepatic GVHD, Hepatitis, Pregnancy, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a combination of chemotherapy drugs to treat patients with certain types of leukemia and lymphoma that have returned or don't respond to usual treatments. The drugs work together to kill cancer cells and stop them from growing. The study aims to see how safe and effective this treatment is.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it does allow hydroxyurea and dexamethasone up to 24 hours before starting the trial. If you are taking a tyrosine kinase inhibitor for Philadelphia positive ALL, you do not need to stop it.

What data supports the effectiveness of the drug combination used in the clinical trial for acute lymphoblastic leukemia?

Research shows that vincristine sulfate liposome injection (VSLI), a part of the drug combination, has been effective in treating relapsed or refractory acute lymphoblastic leukemia (ALL) in adults. It improves drug delivery to target tissues and reduces neurotoxicity, allowing for higher doses and better outcomes in some patients. ^{1 2 3 4 5}

Is the combination chemotherapy treatment generally safe for humans?

Vincristine sulfate liposome injection (VSLI) has been studied in adults with relapsed or refractory acute lymphoblastic leukemia and has shown an acceptable safety profile with no new or unexpected toxicities. The liposomal formulation is designed to reduce neurotoxicity compared to conventional vincristine, allowing for higher doses with improved drug delivery to target tissues. ^{1 2 3 4 6}

What makes this drug combination unique for treating acute lymphoblastic leukemia?

This drug combination is unique because it includes vincristine sulfate liposome injection (VSLI), which is a special formulation that allows higher doses of vincristine to be delivered more effectively to the tissues while reducing the risk of nerve damage, a common side effect of standard vincristine. This formulation can improve outcomes for patients with relapsed or hard-to-treat acute lymphoblastic leukemia. ^{1 2 3 4 5}

Research Team

Maro Ohanian

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for people over 15 with certain types of blood cancers like acute lymphoblastic leukemia or Burkitt lymphoma that have returned or are treatment-resistant. Participants need normal liver function, not be pregnant or breastfeeding, and can't have severe nerve damage or active hepatitis B/C.

Inclusion Criteria

Serum bilirubin =< 1.5 mg/dL

Serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit normal (ULN), with exception for Gilbert's syndrome

I am older than 15 years.

Exclusion Criteria

I have active liver complications from a transplant.

Pregnancy

Breast feeding

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive clofarabine, etoposide, cyclophosphamide, vincristine sulfate liposome, dexamethasone, bortezomib, and possibly ofatumumab or rituximab, with the option for an additional course based on disease response

Approximately 2 weeks per course

Multiple visits for IV and SC administration

Consolidation Therapy

Patients receive clofarabine, etoposide, cyclophosphamide, vincristine sulfate liposome, dexamethasone, bortezomib, and possibly ofatumumab or rituximab, repeated every 28 days for up to 5 courses

Up to 5 months

Multiple visits for IV and SC administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 8 years

Treatment Details

Interventions

• Bortezomib (Proteasome inhibitor)
• Clofarabine (Alkylating agents)
• Cyclophosphamide (Alkylating agents)
• Dexamethasone (Corticosteroid)
• Etoposide (Topoisomerase II inhibitors)
• Vincristine Sulfate Liposome (Vinca alkaloids)

Trial Overview The study tests a combination chemotherapy regimen using drugs like clofarabine, etoposide, cyclophosphamide, and others to see how well they work against aggressive blood cancers when previous treatments failed.

Participant Groups

Group I: Treatment (combination chemotherapy) Experimental Treatment 9 Interventions

See detailed description

Bortezomib is already approved in Canada, Japan for the following indications:

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

Vincristine sulfate liposome injection (Marqibo) showed an overall response rate of 35% in adult patients with relapsed or refractory acute lymphoblastic leukemia when administered at a dose of 2.25 mg/m² once weekly.

The treatment was found to be safe, with no new or unexpected toxicities reported, indicating a favorable safety profile for this formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vincristine sulfate liposome injection: a guide to its use in refractory or relapsed acute lymphoblastic leukemia. Harrison, TS., Lyseng-Williamson, KA.[2016]

Liposomal vincristine (VSLI) shows promise as a treatment for relapsed or refractory acute lymphoblastic leukemia (ALL), potentially inducing complete responses in some adults, which can help them qualify for stem-cell transplantation.

VSLI may enhance drug delivery and reduce neurotoxicity compared to conventional vincristine, which is limited by cumulative toxicity, making it a safer option for patients with ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal vincristine for relapsed or refractory Ph-negative acute lymphoblastic leukemia: a review of literature. Pathak, P., Hess, R., Weiss, MA.[2021]

Vincristine sulfate liposome injection (VSLI) was well tolerated in adolescent and young adult (AYA) patients with advanced acute lymphoblastic leukemia (ALL), with a 25% complete remission rate and an overall response rate of 39% after a median of 5 doses.

The safety profile of VSLI was comparable to traditional vincristine, with serious adverse events occurring in 36% of patients, primarily involving peripheral neuropathy, but no neuropathy-related deaths were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Vincristine Sulfate Liposome Injection, for Advanced, Relapsed, or Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in an Adolescent and Young Adult Subgroup of a Phase 2 Clinical Trial. Schiller, GJ., Damon, LE., Coutre, SE., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Vincristine Sulfate Liposome Injection in the Treatment of Adult Acute Lymphocytic Leukemia. [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Vincristine sulfate liposome injection: a guide to its use in refractory or relapsed acute lymphoblastic leukemia. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Liposomal vincristine for relapsed or refractory Ph-negative acute lymphoblastic leukemia: a review of literature. [2021]

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

Phase 1 multicenter study of vincristine sulfate liposomes injection and dexamethasone in adults with relapsed or refractory acute lymphoblastic leukemia. [2021]

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

High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia. [2021]

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

High-Dose Vincristine Sulfate Liposome Injection, for Advanced, Relapsed, or Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in an Adolescent and Young Adult Subgroup of a Phase 2 Clinical Trial. [2019]