What side effects are associated with this type of intervention?

The most common treatments for Bone Marrow Transplant, particularly Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT), involve conditioning regimens that include chemotherapy agents like fludarabine and melphalan, and total body irradiation (TBI). Known side effects include treatment-related mortality, graft-versus-host disease (GVHD), infections, and organ toxicity. Chronic GVHD can cause long-term complications affecting the skin, liver, and gastrointestinal tract. There is also a risk of secondary malignancies and relapse of the original disease.

What prior FDA approvals exist?

FDA-approved treatments for bone marrow transplants, particularly allogeneic stem cell transplantation (AHSCT), include various conditioning regimens and supportive therapies. Commonly used drugs in these regimens include fludarabine, melphalan, and total body irradiation (TBI), which help to eradicate diseased bone marrow and suppress the immune system to prevent rejection of the donor cells. Additionally, immunosuppressive agents like cyclophosphamide and antithymocyte globulin (ATG) are used to reduce the risk of graft-versus-host disease (GVHD). These treatments are critical in ensuring the success of AHSCT by creating an optimal environment for the engraftment of healthy donor stem cells.

What other types of research exist?

Promising novel alternatives to Allogeneic Stem Cell Transplantation (AHSCT) for bone marrow transplant patients include CAR-T cell therapy and reduced intensity or nonmyeloablative hematopoietic cell transplantation (HCT). CAR-T cell therapy has shown efficacy in certain hematologic malignancies with lower nonrelapse mortality rates. Reduced intensity or nonmyeloablative HCT regimens offer potential benefits by reducing the intensity of the conditioning regimen, thereby lowering treatment-related toxicity while maintaining efficacy.

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Anti-metabolites

Stem Cell Transplant Conditioning for Blood Cancers (ADAPT Trial)

Phase 2

Recruiting

Led By Stefan O. Ciurea, MD

Research Sponsored by University of California, Irvine

Eligibility Criteria Checklist

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

Must have

Diagnosis of AML, ALL, MDS, MPN, CML, NHL, HD, CLL requiring AHSCT

Has an HLA-matched related (MRD), HLA-matched unrelated (MUD), haploidentical (HAPLO) or 1-Ag mismatched unrelated donor (MMUD)

Must not have

Patients with primary CNS lymphoma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 48 months

Awards & highlights

No Placebo-Only Group

Summary

This trial involves replacing damaged bone marrow with healthy donor cells in patients who have not improved with other treatments. The process includes preparation with drugs and radiation, followed by the procedure and medications to prevent complications.

Who is the study for?

Adults aged 18-70 with certain blood cancers like AML, ALL, MDS, and others needing a stem cell transplant can join. They must have a matched donor, good organ function (liver, heart, kidneys), and be able to follow the study plan. Pregnant individuals or those with active infections or CNS diseases cannot participate.

What is being tested?

The trial is testing a new way to prepare patients for stem cell transplants using drugs Fludarabine and Melphalan plus Total Body Irradiation. The doses vary based on each patient's risk factors in this phase II study where everyone gets the same treatment.

What are the potential side effects?

Possible side effects include damage to organs from radiation, low blood counts from chemotherapy which increases infection risk; nausea; mouth sores; liver issues; heart problems; lung changes affecting breathing.

Eligibility Criteria

Inclusion Criteria

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

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I have a blood cancer that needs a stem cell transplant.

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I have a donor that matches my HLA type.

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My bilirubin level is 1.5 mg/dl or lower, except if I have Gilbert's disease.

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I am mostly able to care for myself but may need help.

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I am between 18 and 70 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have been diagnosed with lymphoma that started in my brain or spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 48 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 48 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 48 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-free survival (PFS)

Secondary study objectives

Area Under the Curve (AUC) of Melphalan

Cumulative incidence of Graft-Versus-Host-Free, relapse-free survival (GRFS)

Cumulative incidence of Non-Relapse Mortality (NRM)

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Patients with AML, ALL, MDS, CML, NHL, HD, CLL requiring AHSCTExperimental Treatment3 Interventions

Patients will be treated with allogeneic stem cell transplantation (AHSCT) using fludarabine, melphalan and total body irradiation (TBI) conditioning with different melphalan and TBI doses based on their Hematopoietic Cell Transplant - Composite Risk (HCT-CR), age, and Karnofski performance status (KPS).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fludarabine

2012

Completed Phase 4

~1860

Total Body Irradiation

2006

Completed Phase 3

~820

Melphalan

2008

Completed Phase 3

~1500

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT) replaces diseased or damaged bone marrow with healthy donor stem cells. The primary mechanisms include: 1) High-dose chemotherapy and/or radiation to eradicate malignant cells and create space for new cells. 2) Infusion of healthy donor stem cells to reconstitute the patient's hematopoietic system, leading to the production of healthy blood cells. 3) The graft-versus-tumor effect, where donor immune cells attack residual malignant cells, providing an additional anti-cancer benefit. These mechanisms are vital for BMT patients as they aim to eliminate the disease and restore normal bone marrow function, essential for recovery and long-term health.