Optimizing PTCy Dose and Timing

Summary

Background:

Stem cell or bone marrow transplants can cure or control blood cancers. Sometimes the donor cells see the recipient's body as foreign. This can cause complications. A high dose of the drug cyclophosphamide (PTCy) can help reduce these risks. Researchers want to see if a lower dose of PTCy can have the same benefits. Based on encouraging results from the first part of the study, researchers now are investigating whether a lower dose of PTCy can allow other immunosuppression to be decreased.

Objective:

To see if a lower dose of PTCy and now also shorter duration of another immunosuppressant called mycophenolate mofetil will help people with blood cancers have a more successful transplant and fewer side effects.

Eligibility:

People ages 15-65 with leukemia, lymphoma, or multiple myeloma that is not curable with standard therapy and is at high risk of returning without transplant, and their healthy adult relatives

Design:

Transplant participants will be screened with:

Blood, urine, breathing, and heart tests

Scans

Chest x-ray

Bone marrow samples: A needle inserted into the participant s pelvis will remove marrow and a bone fragment.

Transplant recipients will stay at the hospital and be prepped with chemotherapy over 6 days for the transplant. They will get stem cells through a catheter in the chest or neck. They will get the cyclophosphamide chemotherapy. They will stay in the hospital about 4 more weeks. They will have blood transfusions. They will have frequent blood tests and 2 bone marrow samples within 1 year after the transplant.

Donor participants will be screened with:

Blood, urine, and heart tests

Chest x-ray

Scans

Donor participants will have bone marrow taken from their pelvis or stem cells taken from their blood. For the blood donation, blood will be taken from a vein in one arm, move through a machine to remove white blood cells, and be returned through a vein in the other arm.

Participation will last up to 5 years....

Conditions

• Graft Versus Host Disease
• Hematologic Neoplasms

Interventions

DRUG

Busulfan

Busulfan should be administered intravenously via a central venous catheter as a three-hour infusion every 24 hours.

DRUG

Fludarabine

Fludarabine will be infused by IV over 60 minutes.

DRUG

Cyclophosphamide

IV cyclophosphamide will be administered over 2 hours. Slower rates of infusion may be used to decrease side effects. A fluid intake of greater than 2 L/day is recommended during and for 1 to 2 days after cyclophosphamide administration.

DRUG

Mycophenolate Mofetil

Any oral formulation should be taken on an empty stomach, 1 hour before or at least 2 hours after meals. Oral formulations should not be administered simultaneously with antacids. Avoid inhalation or direct contact with skin or mucous membranes of dry powder contained in capsules or suspension. IV solutions should be administered over at least two hours through either a peripheral or central vein and should not be administered by rapid or bolus injection.

DRUG

Sirolimus

Oral tablets should be administered approximately 4 hours after cyclosporine administration. Sirolimus is administered orally, once daily, without food. Patients unable to tolerate tablets may take the oral solution formulation.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

• National Institute of Neurological Disorders and Stroke (NINDS)

  collaborator NIH

Principal Investigators

• Christopher G Kanakry, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

12 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-07-09

Primary Completion

2025-11-25

Completion

2026-10-26

Countries

• United States

Study Locations