Phase I/II Study to Reduce Post-transplantation Cyclophosphamide Dosing for Older or Unfit Patients Undergoing Bone Marrow Transplantation for Hematologic Malignancies

Summary

Background:

Certain blood cancers can be treated with blood or bone marrow transplants. Sometimes the donor cells attack the recipient's body, called graft-versus-host disease (GVHD). The chemotherapy drug cyclophosphamide helps reduce the risk and severity of GVHD. Researchers want to learn if using a lower dose of cyclophosphamide may reduce the drug's side effects while maintaining its effectiveness. Such an approach is being used in an ongoing clinical study at the NIH with promising results, but this approach has not been tested for transplants using lower doses of chemotherapy/radiation prior to the transplant.

Objective:

To learn if using a lower dose of cyclophosphamide will help people have a successful transplant and have fewer problems and side effects.

Eligibility:

Adults ages 18-85 who have a blood cancer that did not respond well to standard treatments or is at high risk for relapse without transplant, and their donors.

Design:

Participants may be screened with the following:

Medical history

Physical exam

Blood and urine tests

Heart and lung tests

Body imaging scans (they may get a contrast agent)

Spinal tap

Bone marrow biopsy

Participants will be hospitalized for 4-6 weeks. They will have a central venous catheter placed in a chest or neck vein. It will be used to give medicines, transfusions, and the donor cells, and to take blood. In the week before transplant, they will get 2 chemotherapy drugs and radiation. After the transplant, they will get the study drug for 2 days. They will take other drugs for up to 2 months.

Participants must stay near NIH for 3 months after discharge for weekly study visits. Then they will have visits every 3-12 months until 5 years after transplant.

Participants and donors will give blood, bone marrow, saliva, cheek swab, urine, and stool samples for research.

Conditions

• Hematologic Neoplasms

Interventions

DRUG

Mycophenolate Mofetil

15 mg/kg orally or IV three times daily (max 1000 mg/dose) starting on day +5, continued through day +35. May be continued beyond the protocol specified stop date if there is GVHD or mixed chimerism.

PROCEDURE

Allogeneic HSCT

Stem cell transplant

DRUG

Fludarabine

30 mg/m2 IV infusion over 30-60 minutes once daily for 5 days (Pre-Transplant days -6 through -2).

DRUG

Sirolimus

Loading dose of 6 mg orally given on day +5 (calculated based on actual body weight, max initial dose 6 mg), then maintenance dose starting at 2 mg orally daily on day +6 with dose adjustments to maintain a trough of 5-12 ng/ml, continued through day +60 with no taper. May be continued beyond the protocol specified stop date if there is GVHD or mixed chimerism.

DRUG

Filgrastim

begins on day +5 at a dose of 5 mcg/kg/day (actual body weight) IV or subcutaneously, until the absolute neutrophil count is \> 1,000/mm3 over the course of three days or \> 5,000/mm3 on one day. Rounding to the nearest vial is allowed. G-CSF may be stopped early or not administered if required by the clinical circumstance. Additional G-CSF may be administered as warranted.

DRUG

Cyclophosphamide

Pre-transplant: 14.5 mg/kg/day IV daily for 2 days pre-transplant (Pre-Transplant days -6 and -5). Post-transplant: 25 mg/kg/day or 35 mg/kg/day (Post-transplant days +3 and +4).

DRUG

Mesna

25 or 35 mg/kg (equal to the cyclophosphamide dose) as IV infusion concomitant with cyclophosphamide. Mesna may or may not be given with the pre-transplant cyclophosphamide depending on institutional practice.

PROCEDURE

Total Body Irradiation (TBI)

400 centigray (cGy) to be delivered in 2 fractions as 200 cGy per fraction twice daily. Pre-Transplant Day -1 (or Day 0 prior to graft administration)

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

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

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

12 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-09-23

Primary Completion

2027-04-27

Completion

2027-04-30

FDA Drug

Yes

Countries

• United States

Study Locations