Specialized Blood Cell Transplants for Cancers of the Blood and Bone Marrow

Summary

The are a variety of cancerous diseases of the blood and bone marrow that can be potentially cured by bone marrow transplantation (BMT). Diseases like leukemia, lymphoma, and multiple myeloma are among the conditions that can be treated with BMT.

Some patients with these diseases can be treated with medical chemotherapy alone. However, patients who relapse following chemotherapy are usually not curable with additional chemotherapy treatments. The only option known to provide a potential cure if this occurs is BMT.

Allogenic transplants are cells collected from relatives of the patient. The transplant requires additional high intensity chemotherapy and radiation in order to destroy cancerous cells. In the process, many normal bone marrow cells are also destroyed. This is the reason for transplanting stem cells. The stem cells help to build new functioning bone marrow, red cells, white cells, and platelets. In addition, the immune cells from the donor are implanted into the recipient s body and help to fight off infection and kill remaining cancerous cells.

Unfortunately, the powerful doses of chemotherapy and radiation therapy associated with allogenic BMT have toxic side effects and often make BMTs too dangerous to attempt in many patients.

In order to reduce the complications of BMT, and make it a safer available option for patients with cancers of the blood and bone marrow, researchers have developed a new approach to the BMT.

In this study researchers plan to use stem cells collected from the blood stream of patient s relatives rather than from the bone marrow (blood progenitor/stem cell transplant). In addition, researchers plan to use low doses of chemotherapy and no radiation therapy to reduce side effects. The majority of the cancer killing effect will be the responsibility of the stem cell transplant rather than the chemotherapy.

Conditions

• Myeloproliferative Disorders
• Acute Myelogenous Leukemia
• Chronic Myelogenous Leukemia
• Myelodysplastic Syndrome
• Acute Lymphoblastic Leukemia

Interventions

PROCEDURE

T-cell replete PBPC allograft

Subjects will receive a non-myeloablative preparative regimen of cyclophosphamide 60mg/kg/d x 2 days, and fludarabine 25mg/m2 intravenously (IV) over 30 minutes daily x 5 days with or without ATG followed by a PBPC graft targeted to deliver \>5x10\^6 CD34+ cells/kg.

DRUG

Methotrexate

IV MTX on days +1, +3, and +6 will be given

DRUG

Cyclosporine

CSA will be given beginning on day -4 for graft versus host disease prophylaxis. Participants with mixed T-cell chimerism on day 30 will begin a CSA taper. Participants with 100% donor T-cell chimerism by day 30 will be tapered off CSA from days 60 through 100 (25% reduction in dose every 10 days-off by day 100). CSA will not be tapered in any subjects with grade \> II acute GVHD regardless of chimerism results. In addition, participants with evidence of disease progression without grade \> II GVHD will have CSA discontinued regardless of chimerism results.

DRUG

G-CSF

G-CSF will be administered based on body weight for at least 5, and up to 7 days, subcutaneously.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  lead NIH

Principal Investigators

• Richard W Childs, M.D. · National Heart, Lung, and Blood Institute (NHLBI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

2 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

1999-04-15

Primary Completion

2018-12-14

Completion

2020-06-18

FDA Drug

Yes

Countries

• United States

Study Locations