Chemoradiotherapy + Stem Cell Transplant for Blood Cancers

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: City of Hope Medical Center

Disqualifiers: AUL, Fanconi Anemia, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of chemotherapy, radiation therapy, and stem cell transplants to treat blood cancers such as AML (Acute Myeloid Leukemia) and ALL (Acute Lymphoblastic Leukemia). The goal is to halt cancer growth and prevent the immune system from rejecting new stem cells, aiding in the production of healthy blood cells. The trial involves drugs like fludarabine phosphate and melphalan, along with helical tomotherapy, a type of targeted radiation. Suitable participants have confirmed blood cancer diagnoses and can remain still for about 30 minutes during treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that each component of this treatment has been studied for safety. Fludarabine phosphate, an FDA-approved drug for certain blood cancers, can sometimes cause infections, with up to 67% of these infections resulting from unusual germs. Melphalan, another chemotherapy drug used before stem cell transplants, frequently causes low blood cell counts, a common side effect in cancer treatments.

Helical tomotherapy, a type of radiation therapy, has been found safe in other cancer studies and has shown survival benefits in some cases, such as mesothelioma, a cancer affecting the lung lining. Using a donor's stem cells, known as allogeneic hematopoietic stem cell transplantation, is generally safe but carries some risks. These include a small chance of serious complications for the donor and the possibility of cancer returning or a new cancer developing for the patient.

While each part of the treatment has known side effects, the trial aims to manage and balance these risks to effectively stop cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination because it brings together advanced techniques in fighting blood cancers. Unlike standard treatments that typically involve chemotherapy or radiation alone, this approach integrates Fludarabine Phosphate and Melphalan with helical tomotherapy, a precise form of radiation therapy that targets tumors more accurately, minimizing damage to healthy tissues. Additionally, the inclusion of an allogeneic stem cell transplant offers the potential for a more robust immune response against cancer cells. This innovative combination aims to enhance efficacy while reducing side effects, which is a significant advancement over existing therapies.

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

Research has shown that the combination of treatments in this trial—fludarabine phosphate, melphalan, and helical tomotherapy—offers promising results for blood cancers. Participants will receive these treatments as part of the preparative regimen. Fludarabine phosphate has been effective, with over 80% of patients achieving remission in past studies. Melphalan is known for its tumor-fighting ability and has successfully controlled the disease with manageable side effects. Helical tomotherapy has demonstrated good results in controlling the disease and improving survival, with fewer side effects compared to standard treatments. After these therapies, participants will undergo allogeneic hematopoietic stem cell transplantation, which can potentially cure blood-related cancers. Overall, these treatments have shown significant promise in fighting blood cancers, based on existing research. ^{6 7 8 9 10}

Who Is on the Research Team?

Joseph Rosenthal, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with certain blood cancers like AML, high-risk MDS, or ALL. They must be able to lie still in a body cast for treatment sessions and have good heart, lung, liver, and kidney function. Excluded are those with specific leukemia types (AUL), prior extensive radiation therapy, HIV infection, uncontrolled infections or serious recent infections.

Inclusion Criteria

Patients must have less than 15% peripheral blasts

I can lie on my back for 30 minutes without moving, even if it means I might need sedation.

Recipient, or recipient's parents, or recipient's legal guardians must have signed a voluntary, informed consent in accordance with institutional and federal guidelines

Exclusion Criteria

I have had radiation therapy to a large part of my bone marrow or received high-dose radiation.

My leukemia does not show specific cell type markers.

I am HIV positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Participants receive fludarabine phosphate IV on days -7 to -3, melphalan IV on day -2, and undergo helical tomotherapy twice daily on days -7 to -4

1 week

Transplantation

Participants undergo allogeneic hematopoietic stem cell transplantation on day 0

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Hematopoietic Stem Cell Transplantation
• Fludarabine Phosphate
• Helical Tomotherapy
• Melphalan

Trial Overview The study tests helical tomotherapy (HT) combined with chemotherapy drugs fludarabine phosphate and melphalan before an allogeneic stem cell transplant from a donor. The goal is to stop cancer growth and prevent immune rejection of the transplanted cells.

How Is the Trial Designed?

Group I: Treatment (enzyme inhibitor, radiation therapy, transplant) Experimental Treatment 4 Interventions

PREPARATIVE REGIMEN\*: Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2. Patients also undergo helical tomotherapy twice daily on days -7 to -4. TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0. NOTE: \*Treatment begins 2 days earlier in patients receive tacrolimus and/or sirolimus for GVHD prophylaxis.

Fludarabine Phosphate is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Fludara for:

• Chronic lymphocytic leukemia
• Non-Hodgkin's lymphoma
• Acute myeloid leukemia

Approved in European Union as Fludara for:

• Chronic lymphocytic leukemia
• Non-Hodgkin's lymphoma
• Acute myeloid leukemia

Approved in Canada as Fludara for:

• Chronic lymphocytic leukemia
• Non-Hodgkin's lymphoma
• Acute myeloid leukemia

Approved in Japan as Fludara for:

• Chronic lymphocytic leukemia
• Non-Hodgkin's lymphoma
• Acute myeloid leukemia

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2943393/

Allogeneic hematopoietic cell transplantation: the state of ... Early rather than late allogeneic HCT was not only associated with better outcomes but also a decrease in the likelihood of complications that preclude HCT ( ...

2. astctjournal.org astctjournal.org/article/S2666-6367(24)00842-X/fulltext

Outcomes of Allogeneic Hematopoietic Stem Cell ... Allo-HCT offers curative potential for patients aged 70 and above with hematologic malignancies. •. Post-transplant relapse and infection remain the leading ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2531137925001555

OUTCOMES OF ALLOGENEIC STEM CELL ... Allogeneic HSCT offers curative potential for many hematologic malignancies. Transplantation is performed in AML patients to reduce the risk of relapse. A fully ...

4. nature.com nature.com/articles/s41598-025-05602-z

Clinical outcomes of allogeneic hematopoietic stem cell ... This study emphasizes the efficacy of HSCT in the treatment of infant AML, with higher OS rates compared to childhood AML. It also supports UCB as a viable ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4010196/

Hematopoietic Stem Cell Transplantation for Hematologic ... Hematopoietic cell transplantation (HCT) provides a life-prolonging or potentially curative treatment option for patients with hematologic malignancies.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5345733/

Safety and efficacy of allogeneic hematopoietic stem cell ... Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723016408

Risks of Patient and Donor Genetics in Allogeneic ... Up to 30% of patients relapse after allo-HSCT, of which up to 2% to 5% are donor-derived malignancies (DDMs). DDMs can arise from a germline genetic ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2625420/

Severe events in donors after allogeneic hematopoietic stem ... This study shows that hematopoietic stem cell donation is associated with a small but definite risk of fatalities and serious adverse events.

9. bloodcancerunited.org bloodcancerunited.org/blood-cancer-care/adults/types-blood-cancer-treatment/stem-cell-transplantation/allogeneic

Allogeneic stem cell transplantation Allogeneic stem cell transplantation (SCT) involves the use of stem cells donated from another person, related or unrelated.

10. sciencedirect.com sciencedirect.com/science/article/pii/S2666636725014472

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... To identify pertinent articles evaluating the efficacy and safety of HSCT in SCD, a thorough search of 2 databases, namely, PubMed and Scopus, ...