UCB Transplant After Non-Myeloablative Prep for Blood Cancers

Overseen By Timothy Krepski

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Pregnancy, Active infection, HIV, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new approach for treating blood cancers using a less intense preparation method before a cord blood transplant. It aims to determine the method's effectiveness for patients with blood cancers like leukemia or lymphoma, especially those not cured by standard chemotherapy. The trial tests different treatment combinations, including cyclophosphamide, fludarabine, and total body irradiation (TBI), with or without Anti-thymocyte Globulin (ATG). Eligible participants include those with certain blood cancers who have undergone multiple treatments or an unsuccessful previous transplant. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from innovative therapies.

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 coordinators or your doctor.

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

Research has shown that the combination of cyclophosphamide, fludarabine, and total body irradiation (TBI) has been tested in previous studies. These studies generally found that these treatments are well-tolerated, with manageable side effects.

Cyclophosphamide is used in umbilical cord blood transplants and is considered safe. It helps lower the risk of graft-versus-host disease (GVHD), where the transplanted cells attack the body. Studies have shown that this drug, when used with others, has a good safety record.

Fludarabine, another drug in this treatment plan, is often used in bone marrow transplants and is known to be well-tolerated. Research has reported fewer severe side effects with fludarabine, making it a safer choice for patients undergoing transplants.

Total body irradiation (TBI) prepares the body for the transplant. While it carries some risk, studies have found it to be generally safe in umbilical cord blood transplants.

Overall, evidence suggests these treatments are reasonably safe for patients. However, since this is a phase II trial, researchers are closely monitoring it for any side effects. Participants in these trials help researchers learn more about the safety and effectiveness of these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this approach to treating blood cancers because it uses umbilical cord blood transplants after a non-myeloablative preparation, which is less intense than traditional methods. Unlike standard treatments that often involve aggressive chemotherapy or radiation, this method combines cyclophosphamide, fludarabine, and total body irradiation (TBI) to prepare patients more gently for transplant. The trial explores two arms: one without Anti-thymocyte Globulin (ATG) for patients with prior intense treatments, and one with ATG for those with less prior treatment. This tailored approach could potentially reduce treatment-related side effects and improve recovery times, making it a promising alternative for patients who have already undergone significant therapies.

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

Research has shown that combining cyclophosphamide and fludarabine can effectively treat certain blood cancers, such as chronic lymphocytic leukemia. One study found that this combination led to complete remission in 70% of previously untreated patients. Cyclophosphamide destroys cancer cells, while fludarabine enhances this effect. In this trial, participants will receive a regimen either with or without Anti-thymocyte Globulin (ATG) as part of their conditioning. Total body irradiation (TBI) is used in this trial to prepare the body for a stem cell transplant by clearing out existing bone marrow. These treatments work together to eliminate cancer cells and create space for healthy new bone marrow. ^{6 7 8 9 10}

Who Is on the Research Team?

Margaret MacMillan, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for people under 75 with certain blood cancers or bone marrow diseases who don't have a fully matched sibling donor. They must be in good enough health, agree to birth control if they can have children, and give written consent. It's not for pregnant women, those breastfeeding, or patients with specific progressing lymphomas or recent transplants.

Inclusion Criteria

I am physically active and can care for myself.

I am under 70 without a matching sibling donor or between 70 and 75 with low health issues.

My lymphoma is considered bulky.

Exclusion Criteria

My condition is chronic myeloid leukemia in its most advanced stage.

Your tests show that your disease is getting worse.

I have an active brain or spinal cord tumor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Participants receive a non-myeloablative preparative regimen including cyclophosphamide, fludarabine, and total body irradiation (TBI) with modifications based on diagnosis, disease status, and prior treatment

2 weeks

Transplantation

Umbilical cord blood transplantation is performed using single or double unit selected according to the University of Minnesota umbilical cord blood graft selection algorithm

1 week

Follow-up

Participants are monitored for safety and effectiveness, including assessment of acute GVHD and chimerism

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• Sirolimus
• TBI

Trial Overview The study tests a non-myeloablative transplant prep using drugs like cyclophosphamide and fludarabine along with total body irradiation (TBI). Patients will receive umbilical cord blood cells selected by the University of Minnesota's guidelines. The aim is to treat advanced hematologic malignancies.

How Is the Trial Designed?

Group I: No Anti-thymocyte Globulin (ATG) Experimental Treatment 6 Interventions

Hematologic malignancy patients who have received a previous autologous transplant or ≥ 2 cycles of multi-agent chemotherapy within the 3 months previous to umbilical cord blood transplantation.

Group II: Anti-thymocyte Globulin (ATG) Experimental Treatment 7 Interventions

Hematologic malignancy patients who have not been treated with prior autologous transplant or ≤ 1 cycle of chemotherapy in the 3 months previous to umbilical cord blood transplantation, should receive Anti-thymocyte Globulin (ATG) as part of their conditioning regimen.

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Published Research Related to This Trial

In a study of 2910 patients with acute myeloid leukemia (AML) undergoing transplants, the thiotepa-busulfan-fludarabine (TBF) conditioning regimen showed significantly lower relapse rates compared to the busulfan-fludarabine (BF) regimen, but it also resulted in higher non-relapse mortality (NRM).

Despite the stronger anti-leukemic activity of TBF-MAC, overall survival and leukemia-free survival rates were similar to those of BF-MAC, indicating that while TBF may reduce relapse, it does not necessarily improve long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiotepa-busulfan-fludarabine compared to busulfan-fludarabine for sibling and unrelated donor transplant in acute myeloid leukemia in first remission. Saraceni, F., Labopin, M., Hamladji, RM., et al.[2022]

In a study involving 10 adult patients with myeloid malignancies, the combination of once-daily intravenous busulfan and fludarabine as a preparative regimen for umbilical cord blood transplantation resulted in donor-derived neutrophil recovery in only 2 out of 10 patients, indicating poor engraftment.

The findings suggest that this myeloablative conditioning regimen does not provide adequate immunosuppression for successful engraftment of partially matched dual umbilical cord blood grafts, leading to the premature closure of the study due to graft failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myeloablative intravenous busulfan/fludarabine conditioning does not facilitate reliable engraftment of dual umbilical cord blood grafts in adult recipients. Horwitz, ME., Morris, A., Gasparetto, C., et al.[2021]

In a study of 32 patients with acute myeloid leukemia in first complete remission, the busulfan/fludarabine (Bu/Flu) conditioning regimen resulted in significantly lower transplant-related toxicity compared to the busulfan/cyclophosphamide (Bu/Cy) regimen, with a lower incidence of severe side effects (68.8% vs. 25.0%).

Both regimens showed similar efficacy in terms of overall survival and event-free survival rates, indicating that Bu/Flu is a safer option without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A comparison of toxicity and efficacy between busulfan plus fludarabine and busulfan plus cyclophosphamide for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia]. Liu, H., Fan, ZP., Jiang, QL., et al.[2014]

Blisibimod is a highly potent inhibitor of B cell activating factor (BAFF) and is currently being evaluated for its efficacy and safety in treating systemic lupus erythematosus (SLE) in clinical trials, including the ongoing phase 3 CHABLIS-SC1 trial.

The unique tetravalent 'peptibody' structure of blisibimod may enhance its effectiveness, and its targeted approach towards specific 'responder populations' suggests it could become a significant treatment option for both SLE and IgA nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blisibimod for treatment of systemic lupus erythematosus: with trials you become wiser. Scheinberg, MA., Hislop, CM., Martin, RS.[2018]

In a study evaluating three myeloablative regimens for cord blood transplantation in high-risk hematologic malignancies, the third regimen (busulfan, clofarabine, fludarabine, and low-dose total body irradiation) showed low engraftment failure and effective tumor control, suggesting it is a promising option.

While the first regimen led to quick engraftment, it had a high nonrelapse mortality rate, and the second regimen was well tolerated but resulted in high engraftment failure, highlighting the need for careful selection of preparative regimens in cord blood transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development of a myeloablative, reduced-toxicity, conditioning regimen for cord blood transplantation. Mehta, RS., Di Stasi, A., Andersson, BS., et al.[2021]

In a study involving three children who were not ideal candidates for standard conditioning protocols, a fludarabine-based regimen combined with total body irradiation (TBI) and melphalan successfully facilitated umbilical cord blood (UCB) transplantation, leading to successful engraftment in all patients.

Two of the three patients are alive with complete chimerism 8 and 20 months post-transplant, suggesting that a fludarabine-based protocol may be a viable option for selected cases of UCB transplants, despite mild extramedullary toxicity observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine-based preparative protocol for unrelated donor cord blood transplantation in children: successful engraftment with minimal toxicity. Chan, KW., Békássy, AN., Ha, CS., et al.[2013]

In a Phase 2b clinical trial involving 547 patients with systemic lupus erythematosus (SLE), the highest dose of blisibimod (200 mg once-weekly) showed statistically significant improvements in disease response rates compared to placebo, particularly in patients with severe disease.

Blisibimod was found to be safe, with no significant differences in serious adverse events or infections compared to placebo, indicating it could be a viable treatment option for SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study. Furie, RA., Leon, G., Thomas, M., et al.[2022]

Citations

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Final Results from Phase 1 Study of Briquilimab, an Anti- ... Conclusions: These results demonstrate that targeting CD117 with briquilimab together with TBI/Flu as a novel conditioning regimen is safe, well-tolerated, ...

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Subanalysis from Phase 1 Study of Briquilimab (JSP191), ... Briquilimab (JSP191) is an investigational agent and not approved for any indication. Bone marrow aspiration/biopsy. Page 8. Subanalysis of 12 AML Patients with ...

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Early results of phase 1 study of JSP191, an anti-CD117 ... Conclusions: These early results are the first to demonstrate that JSP191/TBI/Flu is safe, well-tolerated, and capable of clearing MDS/AML MRD ...

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Study Details | NCT00864227 | Evaluating the Safety and ... The purpose of the study is to examine the safety and effectiveness of a nonmyeloablative stem cell transplant that uses umbilical cord blood as a treatment ...