Microtransplantation to Treat Refractory or Relapsed Hematologic Malignancies in Younger Patients

NCT ID: NCT02433483

Last Updated: 2017-11-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-22
• Study Completion Date: 2017-05-08

Brief Summary

Allogeneic transplant can sometimes be an effective treatment for leukemia. In a traditional allogeneic transplant, patients receive very high doses of chemotherapy and/or radiation therapy, followed by an infusion of their donor's bone marrow or blood stem cells. The high-dose chemotherapy drugs and radiation are given to remove the leukemia cells in the body. The infusion of the donor's bone marrow or blood stem cells is given to replace the diseased bone marrow destroyed by the chemotherapy and/or radiation therapy. However, there are risks associated with allogeneic transplant. Many people have life-threatening or even fatal complications, like severe infections and a condition called graft-versus-host disease, which is caused when cells from the donor attack the normal tissue of the transplant patient.

Recently, several hospitals around the world have been using a different type of allogeneic transplant called a microtransplant. In this type of transplant, the donor is usually a family member who is not an exact match. In a microtransplant, leukemia patients get lower doses of chemotherapy than are used in traditional allogeneic transplants. The chemotherapy is followed by an infusion of their donor's peripheral blood stem cells. The objective of the microtransplant is to suppress the bone marrow by giving just enough chemotherapy to allow the donor cells to temporarily engraft (implant), but only at very low levels. The hope is that the donor cells will cause the body to mount an immunologic attack against the leukemia, generating a response called the "graft-versus-leukemia" effect or "graft-versus-cancer" effect, without causing the potentially serious complication of graft-versus-host disease.

With this research study, the investigators hope to find out whether or not microtransplantation will be a safe and effective treatment for children, adolescents and young adults with relapsed or refractory hematologic malignancies

Detailed Description

PRIMARY OBJECTIVES:

• To assess the safety and feasibility of standard chemotherapy plus GCSF-mobilized Hematopoietic Progenitor Cell, Apheresis (HPC-A) in pediatric patients with relapsed or refractory hematologic malignancies.
• To estimate the response rates to standard chemotherapy plus GCSF-mobilized HPC-A in pediatric patients with relapsed or refractory hematologic malignancies.

SECONDARY OBJECTIVES:

• To describe the event-free and overall survival of patients treated with standard chemotherapy plus GCSF-mobilized HPC-A.
• To estimate the time to neutrophil and platelet recovery after treatment with standard chemotherapy plus GCSF-mobilized HPC-A.
• To determine the cumulative incidence of acute and chronic graft-versus-host disease (GVHD).

OTHER PRESPECIFIED OBJECTIVES:

• To characterize donor chimerism and microchimerism.

Patients will receive standard chemotherapy followed by infusion of donor peripheral blood mononuclear cells 2 days after the completion of chemotherapy. Patients who have at least a partial response are eligible to receive a second cycle.

Diagnostic lumbar puncture and intrathecal (IT) chemotherapy will be given prior to cycle 1. Patients without evidence of central nervous system (CNS) leukemia will receive no further IT therapy during cycle 1. Patients with CNS disease will receive weekly IT therapy (age-adjusted methotrexate, hydrocortisone, and cytarabine) until the cerebrospinal fluid (CSF) becomes free of leukemia (minimum of 4 doses).

Bone marrow aspiration (BMA) and biopsy to assess response will be performed on approximately day 29 of therapy.

For hematopoietic stem cell mobilization, donors will receive G-CSF (Filgrastim) (Neupogen®) each day for 5 days given subcutaneously (SQ) prior to HPC-A collected by leukapheresis on day 6.

Conditions

Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS)

Keywords

Adolescent; Children; Microtransplant; Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Myeloid Malignancies

Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.

Participants with CNS disease receive weekly age-adjusted intrathecal triples therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses).

Interventions:

• Cycle 1: cytarabine, HPC-A donor infusion
• Cycle 2: Participants who have at least a partial response to Cycle 1 are eligible to receive Cycle 2: cytarabine, HPC-A infusion

Group Type: EXPERIMENTAL

Cytarabine

Intervention Type: DRUG

Given by either intrathecal (IT) or intravenous (IV) route.

Intrathecal Triples

Intervention Type: DRUG

given IT.

HPC-A

Intervention Type: BIOLOGICAL

Given IV.

Interventions

Cytarabine

Given by either intrathecal (IT) or intravenous (IV) route.

Intervention Type: DRUG

Intrathecal Triples

given IT.

Intervention Type: DRUG

HPC-A

Given IV.

Intervention Type: BIOLOGICAL

Other Intervention Names

Cytosine arabinoside; Ara-C; Cytosar®; ITMHA; Methotrexate/hydrocortisone/cytarabine; Donor infusion; Hematopoietic Progenitor Cell, Apheresis

Eligibility Criteria

Inclusion Criteria

• Participants must have a diagnosis of AML or myelodysplastic syndrome (MDS), ALL, and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after HSCT.

• Refractory disease is defined as persistent disease after at least two courses of induction chemotherapy.
• Patients with AML must have ≥ 5% leukemic blasts in the bone marrow or have converted from negative minimal residual disease (MRD) status to positive MRD status in the bone marrow as assessed by flow cytometry. If an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia in the peripheral blood.
• Participant is ≤ 21 years of age (i.e., has not reached 22nd birthday).
• Adequate organ function defined as the following:

• Total bilirubin ≤ upper limit of normal (ULN) for age, or if total bilirubin is > ULN, direct bilirubin is ≤ 1.5 mg/dL
• AST (SGOT)/ALT (SGPT) < 5 x ULN
• Calculated creatinine clearance > 50 ml/min/1.73m^2 as calculated by the Schwartz formula for estimated glomerular filtration rate >
• Left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25%.
• Has an available HPC-A donor.
• Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥ 50% for patients who are > 16 years old.
• Does not have an uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable.
• Patient has fully recovered from the acute effects of all prior therapy and must meet the following criteria.

• At least 14 days must have elapsed since the completion of myelosuppressive therapy.
• At least 24 hours must have elapsed since the completion of hydroxyurea, low-dose cytarabine (up to 200 mg/m^2/day), and intrathecal chemotherapy.
• At least 30 days must have elapsed since the use of investigational agents.
• For patients who have received prior HSCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HSCT. Patients cannot be receiving therapy, including steroids, for GVHD.
• Post-menarchal female has had negative serum pregnancy test within 7 days prior to enrollment.
• Male or female of reproductive potential has agreed to use effective contraception for the duration of study participation.
• Not breastfeeding

• At least 18 years of age.
• Family member (first degree relatives).
• Not pregnant as confirmed by negative serum or urine pregnancy test within 7 days prior to enrollment (if female).
• Not breast feeding.
• Meets donation eligibility requirements as outlined by 21 CFR 1271.

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cookies for Kids' Cancer

OTHER

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey E. Rubnitz, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan: Initial Protocol

View Document

Document Type: Study Protocol and Statistical Analysis Plan: Version 1.0

View Document

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

NCI-2015-00691

Identifier Type: REGISTRY

Identifier Source: secondary_id

MITREL

Identifier Type: -

Identifier Source: org_study_id