Stem Cell Transplant + Chemotherapy for Leukemia and Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Roswell Park Cancer Institute

Disqualifiers: Myelofibrosis, HLA antibodies, HIV, others

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

Compensation: Varies

Number of Visits: 6

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether combining chemotherapy, total body irradiation, and cyclophosphamide (a chemotherapy medication) can reduce the risk of graft versus host disease in people with blood cancers undergoing a stem cell transplant. The goal is to prevent the donor's immune cells from attacking the patient's healthy cells after a transplant. Individuals with blood cancers like leukemia or lymphoma who have identified a matching stem cell donor might be suitable for this trial. As a Phase 1, Phase 2 trial, the research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in blood cancer treatment.

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

The trial protocol does not specify if you need to stop your current medications. It mentions a washout period for prior chemotherapy, but other medications are at the physician's discretion.

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

Research has shown that the combination of fludarabine phosphate, melphalan hydrochloride, and total-body irradiation is usually well-tolerated. Studies have found that this treatment often yields good results with a lower risk of serious side effects.

Cyclophosphamide is administered after stem cell transplants to prevent graft versus host disease, a condition where donor cells attack the patient's body. Evidence suggests it effectively reduces this risk. Most patients manage it well, though some may experience common chemotherapy side effects like nausea or fatigue.

This trial is in its early stages, focusing mainly on understanding safety and determining the best dose. However, these treatments have been used in other contexts, providing some confidence in their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for leukemia and lymphoma, which often include chemotherapy and radiation, this new approach combines stem cell transplants with a sophisticated regimen of drugs like cyclophosphamide, fludarabine phosphate, and sirolimus, alongside total-body irradiation. This combination aims to not only attack the cancer cells but also reset the patient’s immune system, potentially lowering the risk of relapse and complications. Researchers are particularly excited about the inclusion of sirolimus, which helps prevent graft-versus-host disease, a common issue with transplants, by modulating the immune response in a more targeted manner. This innovative approach could offer a more comprehensive and potentially more effective treatment option with long-term benefits.

What evidence suggests that this trial's treatments could be effective for leukemia and lymphoma?

In this trial, participants will receive a combination of fludarabine and melphalan with total-body irradiation (TBI) as part of the conditioning regimen. Studies have shown this approach helps control cancer in patients with blood cancers like leukemia and lymphoma. This combination is practical and can provide long-lasting disease control. Research suggests that adding TBI might enhance the treatment's effectiveness against cancer. After the stem cell transplant, participants will receive cyclophosphamide as part of the graft-versus-host disease (GVHD) prophylaxis regimen, which reduces the risk of donor cells attacking the patient's body. Overall, these treatments have shown promise in improving outcomes for patients with blood cancers. ^{1 2 4 5 6}

Who Is on the Research Team?

Maureen Ross

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with various blood cancers or bone marrow disorders who have a compatible donor for stem cell transplant. They should be in certain disease states, like remission or very good partial response, and have adequate organ function. Participants must not be HIV positive, pregnant, nursing, or have severe myelofibrosis; they need to understand the study and agree to use birth control.

Inclusion Criteria

My leukemia is in partial remission, or my multiple myeloma is responding well to treatment.

Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

I am able to care for myself but cannot do normal activities or work.

Exclusion Criteria

Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study intervention

Your doctor thinks you may have a hard time following the rules for stem cell transplantation due to serious mental health issues or difficult social circumstances.

I am HIV positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Participants receive fludarabine phosphate and melphalan hydrochloride, followed by total body irradiation

5 days

Daily visits for 5 days

Stem Cell Infusion

Participants undergo allogeneic hematopoietic stem cell transplant

1 day

1 visit (in-person)

GVHD Prophylaxis Regimen

Participants receive cyclophosphamide, mycophenolate mofetil, and tacrolimus to prevent graft versus host disease

180 days

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Annual visits

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine Phosphate
• Melphalan Hydrochloride
• Mycophenolate Mofetil
• Sirolimus
• Total-Body Irradiation

Trial Overview The trial tests if chemotherapy combined with total body irradiation and post-transplant cyclophosphamide can reduce graft versus host disease after a donor stem cell transplant. It includes drugs like fludarabine phosphate and melphalan hydrochloride that stop cancer cells from growing.

How Is the Trial Designed?

Group I: Prevention (chemotherapy, TBI, cyclophosphamide) Experimental Treatment 8 Interventions

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1. STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Published Research Related to This Trial

Recent studies on pretransplant conditioning regimens for acute myelogenous leukemia (AML) show mixed results, with some new regimens reducing leukemia relapse but not improving overall leukemia-free survival due to increased mortality from non-leukemia causes.

A subset of new regimens demonstrated improved antileukemia efficacy and leukemia-free survival, but their benefits were not significantly better than traditional treatments like cyclophosphamide and total body radiation, suggesting potential limitations in current clinical trial designs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are new conditioning regimens for transplants in acute myelogenous leukemia better? Aurer, I., Gale, RP.[2019]

In a study of 146 adults with acute lymphoblastic leukemia undergoing transplantation, both conditioning regimens (Cyclophosphamide/Total Body Irradiation vs. Fludarabine/Busulfan/Low-dose TBI) showed similar overall and progression-free survival rates, indicating comparable efficacy.

However, the Fludarabine/Busulfan/Low-dose TBI regimen resulted in a significantly lower relapse rate (18.5% vs. 31.5% for Cy/TBI), suggesting it may be a safer option, especially for patients with poorer performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine, busulfan, and low-dose TBI conditioning versus cyclophosphamide and TBI in allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia. Speziali, C., Daly, A., Abuhaleeqa, M., et al.[2020]

In a study of 2,255 adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic cell transplantation, conditioning with total body irradiation (TBI) plus cyclophosphamide (Cy) significantly reduced the risk of relapse compared to TBI plus fludarabine (Flu), with a relapse rate of 18% versus 30% at 2 years.

While TBI/Cy was associated with a higher risk of grade 2-4 acute graft-versus-host disease (GVHD), it did not significantly affect other transplantation outcomes, suggesting that TBI/Cy may be a preferable conditioning regimen for patients in complete remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT. Giebel, S., Labopin, M., Socié, G., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT00856388

Fludarabine Phosphate, Melphalan, Total-Body Irradiation ... This clinical trial is studying how well giving fludarabine phosphate and melphalan together with total-body irradiation followed by donor stem cell ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33991722/

Outcomes of Fludarabine, Melphalan and Total Body ... Our study shows that Flu-Mel140-TBI seems feasible and provides durable disease control. Addition of TBI did not appear to improve outcomes.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31014757/

Clinical Outcomes of Fludarabine and Melphalan With an ... Patients and methods: We retrospectively evaluated survival outcomes and the efficacy of our fludarabine/melphalan/total body irradiation (TBI) (FMT) regimen.

4. astctjournal.org astctjournal.org/article/S2666-6367(21)00891-5/fulltext

Outcomes of Fludarabine, Melphalan and Total Body ... We hypothesized that addition of 200cGy total body irradiation (TBI) to Flu-Mel140 may improve antitumor activity and transplant outcomes.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04191187

Reduced Intensity Flu/Mel/TBI Conditioning for HAPLO ... This study is designed to estimate disease-free survival (DFS) at 18 months post-transplant. Official Title. Reduced-Intensity Fludarabine, Melphalan, and Total ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00856388?cond=%22Follicular%20Lymphoma%22&intr=%22Thymoglobulin%22&viewType=Table&rank=10

Study Details | Fludarabine Phosphate, Melphalan, Total-Body ... This clinical trial is studying how well giving fludarabine phosphate and melphalan together with total-body irradiation followed by donor stem cell ...