Transplant Conditioning Regimen for Blood Disorders

Recruiting in Palo Alto (17 mi)

+16 other locations

Overseen by Shalini Shenoy, M.D.

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Washington University School of Medicine

Disqualifiers: HIV, Invasive infection, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The hypothesis for this study is that a preparative regimen that maximizes host immunosuppression without myeloablation will be well tolerated and sufficient for engraftment of donor hematopoietic cells. It is also to determine major toxicities from these conditioning regimens, within the first 100 days after transplantation.

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 regimen for blood disorders?

The combination of Campath (Alemtuzumab), Fludarabine, and Melphalan has been shown to be a reasonable preparative regimen for reduced-intensity transplantation, with a low nonrelapse mortality rate, although issues with graft-versus-host disease (GVHD) remain. In pediatric cases, Campath-1H effectively reduced the risk of serious GVHD without increasing life-threatening infections or relapse compared to conventional regimens. ^{1 2 3 4 5}

What makes the transplant conditioning regimen with Campath, Fludarabine, and Melphalan unique?

This regimen is unique because it combines three drugs—Campath (alemtuzumab), Fludarabine, and Melphalan—to prepare patients for a blood stem cell transplant, which is not a standard treatment for many blood disorders. Each drug has a specific role: Campath targets immune cells, Fludarabine suppresses the immune system, and Melphalan is a chemotherapy agent, together creating a comprehensive approach to conditioning before transplantation. ^{6 7 8 9 10}

Research Team

Shalini Shenoy, M.D.

Principal Investigator

Washington University School of Medicine (in St. Louis)

Eligibility Criteria

This trial is for children and young adults under 21 with non-cancerous blood, bone marrow, or metabolic disorders. They must have a matched donor for bone marrow or umbilical cord blood transplant and be in good health otherwise. Pregnant individuals, those with HIV, or active infections cannot participate.

Inclusion Criteria

My Hemoglobin S level is below 30%.

I have a non-cancerous condition and am getting a fully matched bone marrow transplant.

Negative pregnancy test

Exclusion Criteria

I have a serious infection.

Pregnancy/lactating

HIV positive

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Participants undergo a reduced-intensity conditioning regimen to maximize host immunosuppression without myeloablation

2-3 weeks

Transplantation

Hematopoietic stem cell transplantation is performed to achieve donor cell engraftment

1 week

Follow-up

Participants are monitored for safety, effectiveness, and incidence of graft-versus-host disease

100 days

Long-term Follow-up

Participants are monitored for chronic graft-versus-host disease, donor engraftment, immune reconstitution, and overall survival

2 years

Treatment Details

Interventions

• Campath (Monoclonal Antibodies)
• Fludarabine (Anti-metabolites)
• Melphalan (Alkylating agents)

Trial Overview The study tests a new transplant conditioning regimen that uses Campath (an immunosuppressive drug), Fludarabine (a chemotherapy agent), and Melphalan (another chemotherapy) to prepare patients' bodies to accept donor cells without fully destroying their own bone marrow.

Participant Groups

Group I: Stratum 4 Experimental Treatment 3 Interventions

Recipient with non-malignant disorder, excluding hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB

Group II: Stratum 3 Experimental Treatment 3 Interventions

Recipient with hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB

Group III: Stratum 2 Experimental Treatment 3 Interventions

Recipient with transfusion dependent thalassemia. Related or unrelated. 8/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB

Group IV: Stratum 1 Experimental Treatment 2 Interventions

Recipients with non-malignant disorders, excluding thalassemia. Related or unrelated 8/8 HLA-matched bone marrow

Campath is already approved in Canada for the following indications:

Approved in Canada as Campath for:

• Chronic lymphocytic leukemia
• Multiple sclerosis

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

St. Louis University Saint Louis, MO

Columbia University Medical Center New York, NY

University of Calgary Calgary, Canada

Children's Mercy Hospitals and Clinics Kansas City, MO

More Trial Locations

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

St. Louis Children's Hospital

Collaborator

Trials

30

Recruited

83,200+

Findings from Research

The study involved 25 patients with hematologic malignancies undergoing nonmyeloablative transplantation using a regimen that included Campath-1H, which aimed to reduce the risk of graft-versus-host disease (GVHD).

While the regimen showed a low nonrelapse mortality rate of 12% and successful engraftment in most patients, acute GVHD occurred in 40% of cases, indicating that GVHD remains a significant challenge in this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A study of a reduced-intensity conditioning regimen followed by allogeneic stem cell transplantation for patients with hematologic malignancies using Campath-1H as part of a graft-versus-host disease strategy. Shore, T., Harpel, J., Schuster, MW., et al.[2017]

Capecitabine is an effective oral chemotherapy drug that converts to 5-fluorouracil in tumor tissue, making it easier to administer with a good safety profile, particularly in treating metastatic breast and colorectal cancers.

The addition of capecitabine to docetaxel in patients with metastatic breast cancer who had previously received anthracycline treatment significantly improved overall survival, highlighting its efficacy in combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine in the treatment of colorectal cancer. O'Neill, VJ., Cassidy, J.[2015]

The FOLFIRI regimen, which combines irinotecan (CPT-11) with 5-fluorouracil (5-FU) and Leucovorin (LV), has been established as a standard first-line chemotherapy for metastatic colorectal cancer since 2000, based on results from controlled randomized phase III trials.

This regimen requires careful supportive therapy to ensure safe administration, highlighting the importance of managing side effects while maximizing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[FOLFIRI regimen for metastatic or recurrent colorectal cancer]. Uemura, N., Yamada, Y.[2013]

In a phase II study involving 39 patients with advanced colorectal cancer, the combination of irinotecan and 5-fluorouracil showed promising efficacy, with 8 patients achieving an objective response and 12 experiencing disease stabilization, leading to surgical resection in some cases.

The treatment was generally well tolerated, with hematologic toxicity being the most common serious side effect (29% of patients), while the median duration of response was 14 months and median survival was 11 months, indicating a favorable outcome for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective phase II trial of iriontecan, 5-fluorouracil, and leucovorin in combination as salvage therapy for advanced colorectal cancer. Gil-Delgado, MA., Guinet, F., Castaing, D., et al.[2019]

The phase I clinical trial involving 21 patients with metastatic colorectal cancer demonstrated that the combination of CPT-11 with 5-FU and leucovorin is a safe outpatient treatment, with minimal hematologic toxicity and manageable side effects.

The study identified diarrhea as the dose-limiting toxicity at the maximum tolerated dose of 100 mg/m2 of CPT-11, while an 80 mg/m2 dose is recommended for further testing in phase II trials, showing some patients achieved partial responses to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of CPT-11 in combination with 5-fluorouracil plus leucovorin chemotherapy for patients with metastatic colorectal cancer. Yamaguchi, Y., Minami, K., Kawabuchi, Y., et al.[2018]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Acute renal failure and disseminated intravascular coagulation following an idiosyncratic reaction to Alemtuzumab (Campath 1H) or fludarabine. [2017]

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

A study of a reduced-intensity conditioning regimen followed by allogeneic stem cell transplantation for patients with hematologic malignancies using Campath-1H as part of a graft-versus-host disease strategy. [2017]

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

A novel GVHD-prophylaxis with low-dose alemtuzumab in allogeneic sibling or unrelated donor hematopoetic cell transplantation: the feasibility of deescalation. [2017]

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

Pretransplant conditioning with Campath-1H (alemtuzumab) in pediatric matched unrelated hematopoietic stem cell transplants: an institutional experience. [2017]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Alemtuzumab (Campath) in Pediatric Hematopoietic Cell Transplantation: Towards Individualized Dosing to Improve Outcome. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Capecitabine in the treatment of colorectal cancer. [2015]

7. Japan pubmed.ncbi.nlm.nih.gov

[FOLFIRI regimen for metastatic or recurrent colorectal cancer]. [2013]

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

Prospective phase II trial of iriontecan, 5-fluorouracil, and leucovorin in combination as salvage therapy for advanced colorectal cancer. [2019]

9. Greece pubmed.ncbi.nlm.nih.gov

A phase I trial of CPT-11 in combination with 5-fluorouracil plus leucovorin chemotherapy for patients with metastatic colorectal cancer. [2018]

10. Greece pubmed.ncbi.nlm.nih.gov

Irinotecan plus capecitabine as first-line chemotherapy in advanced colorectal cancer. [2018]