Ex Vivo Expansion of Mafosfamide Purged CD34+ Cells in Patients With Acute Leukemia

August 21, 2018 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

RATIONALE: Giving colony-stimulating factors, such as G-CSF, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected. Treating stem cells collected from the patient's blood or bone marrow with chemotherapy in the laboratory removes any remaining cancer cells. Chemotherapy or radiation therapy is given to the patient to prepare the bone marrow for stem cell transplant. The treated stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

PURPOSE: This clinical trial is studying how well an autologous peripheral stem cell or bone marrow transplant using laboratory-treated cells works in treating patients with acute leukemia.

Study Overview

Status

Terminated

Conditions

Leukemia

Intervention / Treatment

Detailed Description

OBJECTIVES:

Determine the feasibility of ex vivo expanded mafosfamide-purged CD34-positive cells for autologous peripheral blood stem cell or bone marrow transplantation in patients with acute leukemia.
Determine the duration of aplasia associated with the use of ex vivo cytokine expanded mafosfamide-purged cells in patients treated with this regimen.
Determine, preliminarily, the event-free survival of patients treated with this regimen.

OUTLINE: This is a pilot study.

Mobilization and stem cell collection: Patients receive cyclophosphamide IV and filgrastim (G-CSF) subcutaneously (SC) or IV once daily for 7-14 days followed by leukapheresis to collect peripheral blood stem cells (PBSCs). Some patients may also undergo bone marrow (BM) harvest if sufficient PBSCs are not collected. Patients with a sufficient number of stem cells or BM (5 x 10^6 PBSC/kg or 3 x 10^8 BM cells/kg) proceed to autologous PBSC transplantation (PBSCT) or BM transplantation (BMT).
CD34-positive cell selection and mafosfamide purging: Collected PBSCs and/or BM are treated in the laboratory to isolate CD34-positive cells. A minimum of 1 x 10^6 nucleated CD34-positive BM cells/kg or 2 x 10^6 nucleated CD34-positive PBSCs/kg must be available after selection to proceed to mafosfamide-purging. The selected cells are then treated in vitro with mafosfamide to purge remaining leukemic cells. One third of the mafosfamide-purged cells are then cryopreserved for future use and 2/3 of the mafosfamide-purged cells proceed to ex vivo expansion.
Ex vivo expansion: The remaining CD34-positive mafosfamide-purged cells are treated in vitro with stem cell factor, G-CSF, and recombinant human thrombopoietin and incubated for 12-14 days.
Myeloablative therapy: Patients receive busulfan on days -9 to -6 and cyclophosphamide on days -5 to -2.
PBSCT or BMT: Patients undergo autologous PBSCT or BMT using CD34-positive mafosfamide-purged cryopreserved cells and ex vivo expanded CD34-positive mafosfamide-purged cells on day 0 followed by G-CSF SC or IV once daily until blood counts recover.

After completion of study treatment, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Maryland
  - Baltimore, Maryland, United States, 21231
    - Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

Diagnosis of acute leukemia meeting 1 of the following criteria:
- High-risk acute myeloid leukemia (AML) in first complete remission (CR) with no matched family donor available, including any of the following types:
  - Secondary AML
  - AML with chromosome 5 or 7 abnormalities
  - AML with trisomy 8
  - AML with 6;9 chromosomal translocation
  - AML with 11q23 chromosomal abnormality
  - AML with multiple or complex chromosomal abnormalities
  - AML with FAB M6 or M7
- AML in second CR (CR2) with no eligible HLA-identical sibling donor available
- High-risk acute lymphoblastic leukemia (ALL) with no eligible HLA-identical sibling donor available, including any of the following types:
  - Philadelphia chromosome-positive ALL
  - ALL with 11q23 chromosomal abnormality
  - ALL in CR2
Eligible for and willing to undergo bone marrow transplantation
No intermediate- or good-risk acute leukemia in CR1

Exclusion Criteria

Availability of a suitable matched HLA-identical sibling marrow donor
Intermediate or good risk acute leukemia in CR1 (39)
Age greater than 70
Weight less than 10 kg
Any risk of pregnancy - all female patients must have an effective form of contraception or be infertile due to hysterectomy, fallopian tube, surgery or premature menopause.
HIV Infection: Patients must be HIV negative for inclusion.
Poor organ function as defined in the BMT Policies and Procedures Manual.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients infused with Mf-treated cells with successful expansion Time Frame: 2 weeks	Number of patients with successful expansion of a CD34 selected, mafosfamide purged autograft.	2 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Event free survival Time Frame: 5 years	5 years
Duration of aplasia as determined by Number of Days to Absolute Neutrophil Count (ANC) recovery Time Frame: 1 month	1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2005

Primary Completion (Actual)

December 1, 2007

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

October 25, 2005

First Submitted That Met QC Criteria

October 25, 2005

First Posted (Estimate)

October 27, 2005

Study Record Updates

Last Update Posted (Actual)

August 23, 2018

Last Update Submitted That Met QC Criteria

August 21, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

J0563 CDR0000453619
P30CA006973 (U.S. NIH Grant/Contract)
P01CA070970 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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