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Radiation

TMLI + Alemtuzumab for Sickle Cell Disease

Phase 1

Recruiting

Led By Joseph Rosenthal

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age: 2-40 years

Creatinine clearance (CrCl) of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (performed within 30 days prior to day 1 of protocol)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

Study Summary

This trial is testing the safety and effectiveness of a new conditioning regimen for stem cell transplantation in patients with sickle cell disease. The conditioning regimen includes total marrow and lymphoid irradiation (TMLI) and alemtuzumab. Alemtuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. The goal of this trial is to reduce organ damage that can be caused by radiation and decrease the risk of graft-versus-host disease (GVHD).

Who is the study for?

This trial is for people aged 2-40 with sickle cell disease who've had severe pain crises or other complications despite treatment, and have a related donor matched on at least 8/10 HLA markers. Participants must be in relatively good health with proper organ function and not pregnant, breastfeeding, or have any active infections or malignancies.Check my eligibility

What is being tested?

The trial tests TMLI and alemtuzumab as a conditioning regimen before stem cell transplantation in sickle cell patients. The goal is to prepare the body for new blood cells, reduce rejection risk, minimize radiation damage to organs, and lower GVHD chances after transplant.See study design

What are the potential side effects?

Potential side effects include immune system reactions due to alemtuzumab that may affect organ function; risks associated with radiation therapy like fatigue and skin changes; plus typical transplant-related complications such as infection risk increase.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 2 and 40 years old.

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My kidney function, measured by creatinine clearance, is good.

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I have a donor who matches at least 8 out of 10 of my HLA markers.

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I have sickle cell disease with a history of stroke or high risk of stroke.

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I am a woman who can have children and my pregnancy test is negative.

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I've had severe pain crises yearly despite treatment.

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I am 60 years old or younger.

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I have a donor who matches at least 8 out of 10 of my HLA markers.

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I have bone damage in two or more joints despite receiving care.

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I have sickle cell disease and am at high risk for serious health problems.

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I am 60 years old or younger.

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My kidney function, measured by creatinine clearance, is good.

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I've had 8 or more blood transfusions yearly for over a year to prevent complications.

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I have had regular blood transfusions (8 or more per year) for over a year to prevent complications.

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I've had severe pain crises yearly despite treatment in the last 2 years.

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My blood clotting time is within the target range for my anticoagulant therapy.

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My blood clotting time is within the normal range and I'm not on blood thinners.

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I have had a stroke or lasting neurological issues.

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I have bone damage in two or more joints despite receiving care.

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I can take care of myself but might not be able to do heavy physical work.

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I've had one or more acute chest syndrome episodes in the last 2 years despite treatment.

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I have had one or more episodes of acute chest syndrome in the last 2 years despite treatment.

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My blood clotting time is within the target range for my anticoagulant therapy.

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I have had repeated priapism treated by a doctor.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Feasibility

Incidence of adverse events

Secondary outcome measures

Disease-free Survival (DFS)

Event-free survival (EFS)

Overall survival (OS)

+3 more

Other outcome measures

Bone marrow environment inflation - levels of inflammatory cytokines

Bone Marrow

Immune cell reconstitution

+2 more

Side effects data

From 2010 Phase 2 trial • 21 Patients • NCT00060424

48%

Neutropenia

10%

Death following disease progression post transplant

10%

Thrombocytopenia

10%

Hyperbilirubinemia

10%

Hypoxia

Typhlitis & Bowel Perforation

Death following progression of GVHD

Cardiac Arrhythmia and Seizure

Death: Sepsis/Renal failure/ with history of GVHD

Severe abnormal pain due to gut GVH

Acute Pulmonary Embolism

Perforated sigmoid diverticulitis

Minimal hydronephosis

Cholecystectomy

Hypotension

Increased creatinine

Neurotoxicity

Renal failure

Tumor lysis syndrome

100%

80%

60%

40%

20%

Study treatment Arm

Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis)

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (TMLI, alemtuzumab)Experimental Treatment4 Interventions

Patients receive alemtuzumab IV over 4 hours QD on days -7 to -3. Patients undergo TMLI BID on day -2. Patients also undergo HCT on day 0 and receive sirolimus on day -1 and day 0.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Alemtuzumab

2004

Completed Phase 4

~1890

Hematopoietic Cell Transplantation

2006

Completed Phase 2

~360

Intensity-Modulated Radiation Therapy

2010

Completed Phase 3

~2160

Sirolimus

2013

Completed Phase 4

~2750

0 / 24Eligibility criteria met

Find a Location

Logistics

Participation is compensated

You will be compensated for participating in this trial.

Who is running the clinical trial?

National Cancer Institute (NCI)NIH

13,658 Previous Clinical Trials

40,924,527 Total Patients Enrolled

City of Hope Medical CenterLead Sponsor

565 Previous Clinical Trials

1,921,440 Total Patients Enrolled

Joseph RosenthalPrincipal InvestigatorCity of Hope Comprehensive Cancer Center

1 Previous Clinical Trials

24 Total Patients Enrolled

Media Library

TMLI (Radiation) Clinical Trial Eligibility Overview. Trial Name: NCT05384756 — Phase 1

Sickle Cell Disease Research Study Groups: Treatment (TMLI, alemtuzumab)

Sickle Cell Disease Clinical Trial 2023: TMLI Highlights & Side Effects. Trial Name: NCT05384756 — Phase 1

TMLI (Radiation) 2023 Treatment Timeline for Medical Study. Trial Name: NCT05384756 — Phase 1

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

Is this experiment enlisting participants aged twenty or above?

"In order to be eligable for this medical trial, applicants must between 12 and 40 years old. There are 131 trials available exclusively to those under 18 while 86 of the studies are accessible only by individuals above 65 years of age."

Answered by AI

Can I take part in this experimental procedure?

"This clinical trial seeks twenty individuals aged between 12 and 40 who currently suffer from anemia due to sickle cell. In addition, patients must be willing to assent as per institutional guidelines; registered into the REMS program; possess an ECOG performance status lower than or equal to 2; have experienced a stroke or neurological deficit lasting longer than 24 hours with increased transcranial Doppler velocity greater than 200 m/s; suffered recurrent priapism necessitating medical intervention; provided informed consent of their own volition or by legal representative if applicable; experienced one more episodes of acute chest syndrome in the past two years despite supportive care measures"

Answered by AI

Has the FDA sanctioned Hematopoietic Cell Transplantation?

"Our team has rated the safety of Hematopoietic Cell Transplantation a 1 as this is currently in its Phase 1 trial, which suggests that there are only limited data to support its efficacy and safety."

Answered by AI

Does this clinical experiment still have the capacity to enroll new participants?

"Affirmative. The clinical trial registry contains evidence that this particular experiment has been recruiting since July 13th 2022, with the most recent update on July 31st 2022. Around 20 patients are being sought from a single medical facility."

Answered by AI

What outcomes is this clinical trial aiming to achieve?

"This trial will have two-year follow up and the primary outcome being monitored is incidence of adverse events. Secondary endpoints include cumulative incidence of chronic GVHD, aGVHD within 100 days post-transplant, and platelet engraftment (defined as independence from transfusions with more than 20x10^9/L)."

Answered by AI

How many participants are sought for this research program?

"Affirmative. The information on clinicaltrials.gov indicates that this medical trial is in a state of active enrollment, having been initially posted on July 13th 2022 and updated most recently on the 31st of July. They are hoping to acquire 20 participants from one site."

Answered by AI

Recent research and studies

clinicaltrials.govStudy

TMLI and Alemtuzumab for Treatment of Sickle Cell Disease

2022. "TMLI and Alemtuzumab for Treatment of Sickle Cell Disease". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT05384756.

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