Combination Chemotherapy, Bone Marrow Transplant, and Post Transplant Cyclophosphamide for Hematologic Cancer

Phase 2

Completed

• Conditions: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes
• Interventions: Drug: Busulfan; Drug: Cyclophosphamide

• Registration Number: NCT00134017
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclophosphamide, mycophenolate mofetil, or tacrolimus after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with tacrolimus and mycophenolate mofetil works in treating patients who are undergoing a donor bone marrow transplant for hematologic cancer.

Detailed Description

OBJECTIVES:

Primary

* Determine the optimal dose of post-transplant immunosuppression comprising high-dose cyclophosphamide, tacrolimus, and mycophenolate mofetil administered after myeloablative conditioning chemotherapy comprising busulfan and cyclophosphamide followed by allogeneic bone marrow transplantation in patients with high-risk hematologic malignancies.

* Determine the incidence and severity of acute graft-versus-host disease in patients treated with this regimen.

* Determine other toxic effects of this regimen in these patients.

Secondary

* Determine immune reconstitution in patients treated with this regimen.

* Determine disease control in patients treated with this regimen.

OUTLINE: This is a pilot study. Patients are stratified according to age (≤ 19 years old vs \> 19 years old).

* Myeloablative conditioning chemotherapy: Patients receive busulfan IV or orally 4 times daily on days -7 to -4 OR days -6 to -3 and cyclophosphamide IV over 1 hour once daily on days -3 to -1 OR days -2 and -1.

* Allogeneic bone marrow transplantation: Patients undergo allogeneic bone marrow transplantation on day 0.

* Immunosuppression therapy: Patients receive high-dose cyclophosphamide IV over 1 hour on days 3 and 4.

After completion of study transplantation, patients are followed at 30 and 60 days, 6 months, 1 year, and then annually thereafter.

Study Timeline

• Study Start: 2004-06
• Study First Submitted: 2005-08-22
• Study First Submitted QC: 2005-08-22
• Study First Posted: 2005-08-24
• Primary Completion: 2010-02
• Study Completion: 2010-02
• Results First Submitted: 2018-07-31
• Status Verified: 2018-08
• Results First Submitted QC: 2018-08-29
• Last Update Submitted: 2018-08-29
• Results First Posted: 2018-08-31
• Last Update Posted: 2018-08-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 142

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bone marrow transplant	Cyclophosphamide	Myeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis
Bone marrow transplant	Busulfan	Myeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Develop Acute Graft-versus-host Disease (GVHD)	Day 100	Percentage of participants who developed grades II-IV and grades III-IV acute GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).

Secondary Outcome Measures

Name	Time	Method
Days to Engraftment	Up to one year	Median number of days to neutrophil and platelet engraftment.
Chimerism	Day 30, Day 60	Number of patients who achieved 100% donor chimerism.
Non-relapse Mortality	Day 100, 2 years	Percentage of participants who died for BMT-related reasons.
Relapse	2 years	Percentage of participants who developed relapse or progressive disease.

Trial Locations

Locations (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States