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

16 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II trial using a non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen with modifications based on factors including diagnosis, disease status, and prior treatment. Single or double unit selected according to current University of Minnesota umbilical cord blood graft selection algorithm.

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.

What data supports the effectiveness of the drug Cyclophosphamide in the treatment of blood cancers?

The research articles provided focus on the use of Cyclophosphamide in treating systemic lupus erythematosus (SLE), not blood cancers. However, Cyclophosphamide is a well-known chemotherapy drug often used in various cancer treatments, including blood cancers, due to its ability to kill rapidly dividing cells. ^{1 2 3 4 5}

How is the UCB transplant treatment with Cyclophosphamide, Fludarabine, and TBI different from other treatments for blood cancers?

This treatment is unique because it uses a non-myeloablative (less intense) approach, which means it is less harsh on the body compared to traditional myeloablative regimens, potentially reducing side effects while still preparing the body for a cord blood transplant. ^{6 7 8 9 10}

Research Team

Margaret MacMillan, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: No 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: 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+

Findings from Research

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 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]

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 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 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]

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 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]

References

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

Long-term effects of combined B-cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus: 2-year results. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of belimumab/low-dose cyclophosphamide therapy in moderate-to-severe systemic lupus erythematosus. [2022]

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

Comparison of safety, efficacy and cost between oral pulse cyclophosphamide versus intravenous cyclophosphamide pulse therapy in severe systemic lupus erythematosus. [2021]

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

Blisibimod for treatment of systemic lupus erythematosus: with trials you become wiser. [2018]

5. England 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. [2022]

6. United States 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Fludarabine-based preparative protocol for unrelated donor cord blood transplantation in children: successful engraftment with minimal toxicity. [2013]

8. China 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]. [2014]

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

The development of a myeloablative, reduced-toxicity, conditioning regimen for cord blood transplantation. [2021]

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

Myeloablative intravenous busulfan/fludarabine conditioning does not facilitate reliable engraftment of dual umbilical cord blood grafts in adult recipients. [2021]