Pre-Transplant Clofarabine + Melphalan for Myelodysplastic Syndrome and Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Radiation therapy

Disqualifiers: Prior transplant, Hepatitis, CNS leukemia, 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: 60

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, clofarabine (also known as Clolar or Evoltra) and melphalan, administered before a stem cell transplant to treat certain blood cancers like myelodysplastic syndrome and leukemia. The researchers aim to determine if these drugs can prevent cancer recurrence and reduce side effects compared to standard treatment. Participants should have myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute leukemia in remission and be eligible for a stem cell transplant. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor to get specific guidance based on your situation.

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

Research has shown that the combination of clofarabine and melphalan has been studied in patients with blood disorders like myelodysplastic syndromes (MDS) and acute leukemia. Clofarabine may cause side effects, such as hand-foot syndrome (a skin reaction), liver problems, and other skin issues. However, it is generally considered safe when administered at the correct dose. Melphalan, another chemotherapy drug, works by stopping cancer cells from growing.

Both drugs are already used in other cancer treatments, so their safety is well understood. While side effects can occur, they are often manageable with medical care. The current trial explores their combined use before a stem cell transplant, aiming to prevent cancer recurrence and cause fewer side effects than standard treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using clofarabine and melphalan as a pre-transplant treatment for myelodysplastic syndrome and leukemia because these drugs work together in a unique way. Clofarabine is designed to disrupt cancer cells' DNA, which makes them more vulnerable to melphalan, a chemotherapy agent that further damages the cancer cells. This combination aims to more effectively prepare the body for a stem cell transplant, potentially improving the transplant's success and reducing the risk of relapse. By targeting cancer cells more precisely and aggressively before the transplant, this regimen could offer a significant advantage over traditional pre-transplant conditioning therapies.

What evidence suggests that clofarabine and melphalan might be effective for myelodysplastic syndrome and leukemia?

This trial will evaluate the use of clofarabine and melphalan before a stem cell transplant for patients with myelodysplastic syndrome and leukemia. Studies have shown that this combination can be effective, with research indicating a one-year survival rate of 71.4% without relapse or GVHD. GVHD, or graft-versus-host disease, occurs when donor cells attack the patient's body, so avoiding it is important. The combination is generally well-tolerated and can help control the disease before the transplant. Although some studies have shown mixed results, this combination shows promise in preventing cancer from returning after a transplant. ^{6 7 8 9 10}

Who Is on the Research Team?

Monzr Al Malki

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with myelodysplasia, acute leukemia in remission, or chronic myelomonocytic leukemia who haven't had a previous transplant. They must have good kidney and liver function, heart and lung capacity, an HLA-matched donor available, and be able to understand the study. Pregnant women or those with significant health issues like HIV are excluded.

Inclusion Criteria

The stem cells used for donation can come from either the blood or the bone marrow.

You rely on regular blood transfusions to maintain your health.

You have a type of blood disorder called therapy-related MDS or MDS that developed from another blood disorder, except for myelofibrosis.

Exclusion Criteria

Patients who have received a prior autologous or allogeneic transplant are excluded

Patients with significant hepatic dysfunction (not meeting liver function tests [LFT] eligibility criteria)

Patients with MDS evolved into AML that is not in remission

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Participants receive clofarabine IV over 2 hours on days -9 to -5 and melphalan IV over 30 minutes on day -4

6 days

Transplant

Participants undergo allogeneic hematopoietic stem cell transplant on day 0

1 day

GVHD Prophylaxis

Participants receive tacrolimus IV or PO and sirolimus PO once daily starting on day -3 with taper per City of Hope standard operating procedure

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Once weekly for 60 days, at 100 and 180 days, at one year, and then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Clofarabine
• Melphalan
• Sirolimus
• Tacrolimus

Trial Overview The effectiveness of clofarabine and melphalan chemotherapy before receiving stem cells from a donor is being tested. The goal is to see if this treatment can help stop cancer growth while preventing rejection of the new stem cells which could rebuild healthy blood cells.

How Is the Trial Designed?

Group I: Treatment (clofarabine, melphalan, transplant) Experimental Treatment 6 Interventions

CONDITIONING REGIMEN: Patients receive clofarabine IV over 2 hours on days -9 to -5 and melphalan IV over 30 minutes on day -4. TRANSPLANT: Patients undergo allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS: Beginning on day -3, patients receive tacrolimus IV or PO and sirolimus PO once daily with taper per City of Hope standard operating procedure.

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

Approved in United States as Clolar for:

• Acute lymphoblastic leukemia (ALL) in pediatric patients

Approved in European Union as Evoltra for:

• Acute lymphoblastic leukemia (ALL) in pediatric patients

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Melphalan has been a key drug in hematopoietic stem cell transplantation (SCT) for over 50 years due to its strong myeloablative properties and effectiveness against various cancers, particularly multiple myeloma and lymphomas.

Combining melphalan with newer agents like bortezomib or lenalidomide may enhance its antitumor effects, while its low toxicity profile makes it a promising backbone for future cellular therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fifty years of melphalan use in hematopoietic stem cell transplantation. Bayraktar, UD., Bashir, Q., Qazilbash, M., et al.[2021]

EVOMELA, a new formulation of melphalan that is free from propylene glycol, has been shown to be safe and effective for high-dose conditioning in autologous stem cell transplantation for multiple myeloma, with a 100% overall response rate in a study of 61 patients.

The study reported low incidences of severe side effects, such as grade 3 mucositis (10%) and stomatitis (5%), indicating that EVOMELA has an acceptable safety profile compared to traditional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation. Hari, P., Aljitawi, OS., Arce-Lara, C., et al.[2017]

Melflufen, a derivative of melphalan, demonstrated significantly higher potency against lymphoma cells compared to melphalan, with IC50 values showing up to 49-fold superiority in cell lines and an average of 108-fold in primary cultures.

In preclinical studies, melflufen showed effective cytotoxicity with minimal side effects in a xenograft model, indicating its potential as a safer and more effective treatment option for relapsed or refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo activity of melflufen (J1)in lymphoma. Delforoush, M., Strese, S., Wickström, M., et al.[2019]

Citations

1. clinicaltrial.be clinicaltrial.be/en/details/12321?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Clofarabine and Melphalan Before Donor Stem Cell ... CONDITIONING REGIMEN: Patients receive clofarabine intravenously (IV) over 2 hours on days -9 to -5 and melphalan IV over 30 minutes on day -4.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10815844/

Clofarabine Preconditioning followed by Allogeneic ... One-year GVHD-free relapse-free survival (GFRS) at 1-year was 71.4% (95% CI: 25.8–92%). Our patients showed successful outcomes with clofarabine ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01885689?cond=%22Acute%20Leukemia%22&intr=%22Sirolimus%22&viewType=Table&rank=7&tab=results

Clofarabine and Melphalan Before Donor Stem Cell ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3423318/

Phase I-II Study of Clofarabine-Melphalan-Alemtuzumab ... It is well tolerated and effective in patients with leukemia and lymphoma entering transplantation with disease control, but has shown disappointing results in ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666636724001805

Comparison of Melphalan Dose in Patients with ... Our findings suggest the superiority of FM140 in patients with MDS undergoing allo-HSCT, especially in high-risk patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11770834/

Phase II Study of Low-Dose Clofarabine Plus Cytarabine ... The outcome of patients with higher-risk myelodysplastic syndromes (MDS) after hypomethylating agent (HMA) failure is poor. We evaluated the safety and activity ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01003678

Safety and Tolerability of Oral Clofarabine in Intermediate ... This is a Phase I trial for patients with intermediate or high risk myelodysplastic syndrome (MDS). The study agent, clofarabine, is produced by Genzyme ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4477686/

Clofarabine-associated acute kidney injury in patients ... The established safety profile for clofarabine includes dose-limiting toxicities of hand–foot syndrome, liver function abnormalities, skin toxicity and systemic ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1040842814001693

The role of Clofarabine in the treatment of adults with acute ... The therapeutic scenario available for adult patients with acute myeloid leukemia (AML) has shown only partial progresses over the last few years.

10. aetna.com aetna.com/cpb/medical/data/800_899/0867.html

Clofarabine (Clolar) - Medical Clinical Policy Bulletins In a prospective, phase II clinical trial, Chevallier et al (2014) evaluated the safety and effectiveness of a clofarabine, intravenous busulfan and anti- ...