Stem Cell Transplant for Aplastic Anemia

TK
Overseen ByTimothy Krepski
Age: Any Age
Sex: Any
Trial Phase: Academic
Sponsor: Masonic Cancer Center, University of Minnesota
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with dyskeratosis congenita or severe aplastic anemia. Patients first receive a special mix of medications, including Alemtuzumab (also known as Campath, Lemtrada, or MabCampath), Anti-thymocyte globulin, Cyclophosphamide (also known as Cytoxan, Neosar, or Endoxan), and Fludarabine (also known as Fludara, Oforta, or Beneflur), followed by a stem cell transplant. The goal is to determine if this combination can improve bone marrow function, reducing the need for red blood cell and platelet transfusions. Individuals experiencing frequent transfusions or diagnosed with these conditions and bone marrow failure might be suitable candidates. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatment options.

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

The trial information does not specify if 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?

In a previous study, alemtuzumab demonstrated that 67% of patients with severe aplastic anemia survived for six years, although it can weaken the immune system for up to two years. Anti-thymocyte globulin (ATG) achieved a response rate of about 70% to 77% within the first year. However, patients using rabbit ATG experienced lower survival rates.

Research has shown that cyclophosphamide can lead to high survival rates, with up to 75% of patients surviving eight years after treatment, especially when combined with total body irradiation. Fludarabine-based treatments have demonstrated an 83.7% survival rate, with some studies reporting 100% survival in certain situations.

Hematopoietic stem cell transplants (HSCT) have demonstrated impressive long-term survival rates, often above 75%, making them a promising option for bone marrow failure. Combining total body irradiation with HSCT has also resulted in excellent outcomes, with survival rates over 75%.

These treatments are generally well-tolerated, but side effects like weakened immunity and other complications can occur. Each treatment has its own risks and benefits, so discussing these with a healthcare provider is important before deciding to participate in a clinical trial.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for aplastic anemia because they employ a unique combination of medications and techniques that could improve outcomes for patients. Unlike standard treatments, which typically involve immunosuppressive therapy or bone marrow transplants from matched donors, these investigational arms incorporate a fludarabine-based preparative regimen. This regimen includes novel combinations of drugs like alemtuzumab and anti-thymocyte globulin, as well as total body irradiation, to optimize the body's readiness for a stem cell transplant. By exploring these diverse approaches, researchers hope to enhance the efficacy and safety of stem cell transplants, potentially offering new solutions for patients with severe aplastic anemia and related conditions.

What evidence suggests that this trial's treatments could be effective for aplastic anemia?

Research has shown that a treatment plan combining fludarabine, cyclophosphamide, antithymocyte globulin (ATG), and total body irradiation (TBI) is promising for severe aplastic anemia. In this trial, participants in arms B, C, and E will receive this regimen followed by a stem cell transplant. Studies have found that this approach leads to high survival rates, with some reports indicating that over 75% of patients survive for at least eight years. This method is particularly effective for patients receiving transplants from unrelated donors, offering hope for those without a matching family donor.

For dyskeratosis congenita, a condition where the body struggles to produce enough blood cells, participants in arms A and D will receive a stem cell transplant using alemtuzumab and fludarabine. The survival rate for patients using similar treatments is about 71%, comparable to other less intense treatment options. These treatments aim to replace the faulty blood system with healthy donor cells, providing a lifeline to those affected.26789

Who Is on the Research Team?

JT

Jakub Tolar, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for people aged 0-70 with dyskeratosis congenita or severe aplastic anemia needing blood transfusions. Participants must have specific blood counts, organ function levels, and genetic mutations related to the conditions. Pregnant individuals, those with uncontrolled infections, certain liver issues, or a diagnosis of Fanconi anemia are excluded.

Inclusion Criteria

My kidney function is at least 30% of what is expected.
Your body is rejecting a transplanted organ, as shown by a specific test.
My heart pumps well and I don't have heart failure.
See 27 more

Exclusion Criteria

I have severe liver damage or hepatitis.
I have received radiation therapy before (applies only if I have severe aplastic anemia).
I have been diagnosed with Fanconi anemia.
See 3 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Participants receive a fludarabine-based preparative regimen including alemtuzumab, cyclophosphamide, and fludarabine, followed by a stem cell transplant

6 weeks

Engraftment Monitoring

Participants are monitored for neutrophil and platelet engraftment

42 days

Follow-up

Participants are monitored for regimen-related mortality, acute and chronic graft-versus-host disease, and secondary malignancies

1 year

What Are the Treatments Tested in This Trial?

Interventions

  • Alemtuzumab
  • Anti-thymocyte globulin
  • Cyclophosphamide
  • Fludarabine
  • Hematopoietic Stem Cell Transplant
  • Total Body Irradiation
Trial Overview The study tests a fludarabine-based regimen followed by stem cell transplant from donors in patients with bone marrow failure due to dyskeratosis congenita or aplastic anemia. It compares three regimens based on disease severity and donor match.
How Is the Trial Designed?
5Treatment groups
Experimental Treatment
Group I: Arm E: Severe Aplastic Anemia (SAA), PTCy platformExperimental Treatment6 Interventions
Group II: Arm D: Dyskeratosis Congenita (DKC), PTCy platformExperimental Treatment4 Interventions
Group III: Arm C: Severe Aplastic Anemia (matched related donor)Experimental Treatment6 Interventions
Group IV: Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)Experimental Treatment6 Interventions
Group V: Arm A Dyskeratosis Congenita (DKC) (non-haploidentical donor)Experimental Treatment4 Interventions

Alemtuzumab is already approved in United States, European Union for the following indications:

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Approved in United States as Campath for:
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Approved in European Union as Lemtrada for:
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Approved in European Union as Campath for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials
285
Recruited
15,700+

Citations

Real-World Retrospective Analysis of Alemtuzumab Outcomes ...Patients were switched to alemtuzumab mainly because of a lack of effectiveness (70.8%), followed by positivity for anti-John Cunningham virus ...
A Reduced-Intensity Conditioning Regimen for Patients ...We report an overall survival of 71%, which is comparable to other recent reports of HSCT with RIC for DC without exposure to potentially damaging radiation 18, ...
Hematopoietic Stem Cell Transplant for Dyskeratosis ...Alemtuzumab 0.2 mg/kg IV over 2 hours on days -10 to -6 from transplant. ... Fludarabine 40 mg/m2 IV over 1 hour on days -6 to -2 from transplant. Other Names:.
Alemtuzumab levels impact acute GVHD, mixed chimerism ...We collected data from 105 patients to examine the influence of peritransplant alemtuzumab levels on acute GVHD, mixed chimerism, and lymphocyte recovery. The ...
Survival after Hematopoietic Stem Cell Transplant in ...The outcome of 109 patients found in the literature was poor, with 5- and 10-year survival estimates of only 57% and 23%, respectively. Patients transplanted ...
Alemtuzumab in Relapsed Immune Severe Aplastic AnemiaAt 6 months, there were improved hematologic response and 3-year survival (37% and 83%, respectively) in patients with refractory SAA treated with alemtuzumab, ...
Alemtuzumab levels impact acute GVHD, mixed chimerism ...We hypothesized that higher levels of alemtuzumab at day 0 would result in a low risk of acute GVHD, a higher risk of mixed chimerism, and ...
The state of the art in the treatment of severe aplastic anemiaInitial reports on haploHCT showed an engraftment rate of 67% and a 2-year OS of 78% in 33 patients (39% children) transplanted between 2011 and 2017 with PTCy ...
9.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/37021397/
Alemtuzumab in relapsed immune severe aplastic anemiaOverall survival was 67% at median follow-up of 6 years. Prolonged iatrogenic immunosuppression was observed as long as 2 years after ...
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