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

72 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well clofarabine and melphalan before a donor stem cell transplant works in treating patients with a decrease in or disappearance of signs and symptoms of myelodysplasia or acute leukemia (disease is in remission), or chronic myelomonocytic leukemia. Giving chemotherapy, such as clofarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into a patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving clofarabine and melphalan before transplant may help prevent the cancer from coming back after transplant, and they may cause fewer side effects than standard treatment.

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.

What data supports the effectiveness of the drug combination of clofarabine and melphalan for treating myelodysplastic syndrome and leukemia?

Research shows that clofarabine, when combined with melphalan, is well-tolerated and effective as a conditioning regimen for stem cell transplantation in patients with advanced acute myelogenous leukemia, with most patients achieving complete engraftment. Additionally, clofarabine has shown substantial activity against myelodysplastic syndrome, making it a potential treatment option for this condition. ^{1 2 3 4 5}

Is the combination of clofarabine and melphalan generally safe for humans?

The combination of clofarabine and melphalan has been studied in various clinical trials, showing it is generally well-tolerated, though some patients experienced serious side effects like multiorgan toxicity and renal failure, especially in older patients. The safety profile is considered acceptable for certain conditions, but there are risks, particularly with kidney-related issues. ^{1 2 3 6 7}

What makes the drug combination of Clofarabine and Melphalan unique for treating myelodysplastic syndrome and leukemia?

The combination of Clofarabine and Melphalan is unique because it serves as a reduced-intensity conditioning regimen for stem cell transplantation, which may be better tolerated by patients with advanced leukemia. Clofarabine is a novel drug with both immunosuppressive and antileukemia properties, enhancing the effectiveness of Melphalan, a long-standing chemotherapy agent, in preparing patients for transplantation. ^{1 2 3 8 9}

Research Team

Monzr Al Malki

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

In vitro and in vivo activity of melflufen (J1)in lymphoma. [2019]

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

A phase I study in adults of clofarabine combined with high-dose melphalan as reduced-intensity conditioning for allogeneic transplantation. [2018]

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

A novel clofarabine bridge strategy facilitates allogeneic transplantation in patients with relapsed/refractory leukemia and high-risk myelodysplastic syndromes. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Clofarabine in the treatment of myelodysplastic syndromes. [2023]

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

Phase I/II study of clofarabine, etoposide, and mitoxantrone in patients with refractory or relapsed acute leukemia. [2018]

6. United States 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. [2017]

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

Phase I-II study of clofarabine-melphalan-alemtuzumab conditioning for allogeneic hematopoietic cell transplantation. [2021]

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

Fifty years of melphalan use in hematopoietic stem cell transplantation. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Refractory acute lymphoblastic leukemia in Chinese children: bridging to stem cell transplantation with clofarabine, cyclophosphamide and etoposide. [2022]