## Protocol Section
### Identification Module
**NCT ID:** NCT00619879

**Brief Title:** Myeloablative Hematopoietic Progenitor Cell Transplantation (HPCT) for Pediatric Malignancies

**Official Title:** Myeloablative Hematopoietic Progenitor Cell Transplantation (HPCT) for Pediatric Malignancies

#### Organization Study ID Info
**ID:** SCT 0307
#### Organization
**Class:** OTHER
**Full Name:** Ann & Robert H Lurie Children's Hospital of Chicago
### Status Module
#### Completion Date
**Date:** 2020-01

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** RECRUITING
#### Last Update Post Date
**Date:** 2011-03-30

**Type:** ESTIMATED

**Last Update Submit Date:** 2011-03-29

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2020-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2007-03

**Status Verified Date:** 2011-03

#### Study First Post Date
**Date:** 2008-02-21
**Type:** ESTIMATED
**Study First Submit Date:** 2008-01-08
**Study First Submit QC Date:** 2008-02-07
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Ann & Robert H Lurie Children's Hospital of Chicago

#### Responsible Party

**Old Name Title:** Morris Kletzel, MD

**Old Organization:** Children's Memorial Hospital

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The purpose of this study is to show that myeloablative hematopoietic progenitor cell transplantation (HPCT) continues to offer acceptable disease-free survival for select patients requiring HPCT.

**Detailed Description:** Myeloablative hematopoietic progenitor cell transplantation (HPCT) remains the standard of care for patients requiring HPCT. The purpose of this study is to evaluate the morbidity and mortality of myeloablative HPCT at Children's Memorial Hospital. It will also look to determine the toxicity of a single conditioning regimen consisting of total body irradiation (TBI), etoposide (VP-16), and Cyclophosphamide for patients with transplant eligible lymphoid malignant conditions or with transplant eligible myeloid malignant conditions who are receiving cord blood units, or to determine the toxicity of a single conditioning regimen consisting of Busulfan and Cyclophosphamide for patients with transplant eligible myeloid malignant conditions who are not receiving cord blood units.

### Conditions Module

**Conditions:**

- Leukemia, Myelogenous, Chronic

- Leukemia, Lymphoblastic, Acute

- Leukemia, Myelogenous, Acute

- Myeloproliferative-Myelodysplastic Diseases

- Lymphoma, Malignant

**Keywords:**

- Leukemia, Myelogenous, Chronic

- Leukemia, Lymphoblastic, Acute

- Leukemia, Myelogenous, Acute

- Myeloproliferative-Myelodysplastic Diseases

- Juvenile Myelomonocytic Leukemia

- Dysmyelopoietic Syndromes

- Lymphoma, Malignant

- Stem Cell Transplantation, Hematopoietic

- Allogeneic Transplantation

- Human Leukocyte Antigens

- Busulfan

- Total Body Irradiation

- VP-16

- Etoposide

- Cyclophosphamide

- Graft-Versus-Host Disease

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 200

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

### Interventions

#### Intervention 1

**Description:** Total Body Irradiation (TBI) 1200 cGy will be given on days -8,-7,-6 and -5 in eight sessions, delivering 150cGy in each session.

Etoposide 1000 mg/m2 as a 24 hour continuous infusion started on day -4.

Cyclophosphamide 60 mg/kg/day IV given over 1 hour daily on days -3, -2.

**Name:** Myeloablative Chemotherapy Regimen for Lymphoid Malignancies or Cord Blood Unit Recipients

**Type:** DRUG

#### Intervention 2

**Description:** Busulfan administration:

* For children \>/= 4 years of age, Busulfan 0.8 mg/kg/dose will be given every 6 hours over days -8,-7, -6, and -5 for a total of 16 doses.
* For children \< 4 years of age, Busulfan 1 mg/kg/dose will be given every 6 hours over days -8, -7, -6, -5 for a total of 16 doses.
* Pharmacokinetic analysis will guide dose modifications targeted to receive an average AUC of 800-1200 microMols\*min for the 16 doses.

Lorazepam (0.05 mg/kg) IV will be administered one half hour before the initial dose of Busulfan is given and every 6 hours through day -4.

Etoposide 1000 mg/m2 as a 24 hour continuous infusion started on day -4.

Cyclophosphamide 60 mg/kg/day IV given over 1 hour daily on days -3 and -2.

**Name:** Myeloablative Chemotherapy Regimen for Non-Cord Blood Unit Recipients with Myeloid Malignancies

**Type:** DRUG

#### Intervention 3

**Description:** Hematopoietic progenitor cells (HPCs) will be infused on day 0. Source of cells may be bone marrow, peripheral blood cells, or cord blood units, from matched related or unrelated donors.

**Name:** Hematopoietic Progenitor Cell Transplantation (HPCT)

**Type:** OTHER

#### Intervention 4

**Description:** Patients with prior CNS disease over the age of 1 year will be treated with 600 cGy of cranial irradiation in addition to 1200 cGy of TBI.

Patients diagnosed with ALL with CNS disease (at the time of diagnosis or relapse) \< 1 year of age will receive CNS treatment as Intrathecal Methotrexate as follows:

* Infants ≤ 1 year of age at the time of Intrathecal Therapy will receive a dosing of 7.5 mg once a month for 6 months after transplant beginning at day +30 with an adequate white count
* Children 1-2 years of age at the time of Intrathecal Therapy will receive 8 mg once a month for 6 months after transplant beginning at day +30 with an adequate white count

**Name:** CNS radiation treatment for ALL with prior CNS disease patients

**Type:** RADIATION

### Outcomes Module

#### Primary Outcomes

**Measure:** Evaluate the morbidity and mortality of hematopoietic progenitor cell transplantation (HPCT) at Children's Memorial Hospital.

**Time Frame:** To study end

#### Secondary Outcomes

**Measure:** Evaluate the effectiveness of graft versus host disease prevention with a combination of anti-thymocyte globulin, continuous infusion cyclosporine, and short course methotrexate for transplants.

**Time Frame:** To study end

**Measure:** Determine the toxicity of a single conditioning regimen consisting of total body irradiation, etoposide, and Cyclophosphamide for patients with transplant eligible lymphoid malignant conditions or myeloid malignant conditions receiving cord blood units.

**Time Frame:** To study end

**Measure:** Determine the toxicity of a single conditioning regimen consisting of Busulfan and Cyclophosphamide for patients with transplant eligible myeloid malignant conditions who are not receiving cord blood units.

**Time Frame:** To study end

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Malignant Disease

  * Chronic myleogenous leukemia in chronic or accelerated phase
  * Acute lymphoblastic leukemia (ALL)

    * First remission high-risk ALL (Ph+, t( 4-11) infants).
    * Second remission ALL, after a short first remission (\<36 mos from Dx).
    * 3rd or greater remission ALL.
  * Acute myelogenous leukemia (AML)

    * First remission high risk acute nonlymphoblastic (ANLL) (as defined by cytogenetics), if a matched sibling donor is available.
    * Initial partial remission AML (\<20% blasts in the bone marrow).
    * AML that is refractory to two cycles of induction therapy.
    * Second or greater remission AML
  * Myelodysplastic/Myeloproliferative Disease

    * Juvenile Myelomonocytic Leukemia (JMML)
    * Myelosplastic syndrome and/or pre-leukemia at any stage
  * Lymphoma

    * Relapsed lymphoma with residual disease that appears to be chemo-sensitive and non-bulky (\<5 cm at largest diameter)
* Venous Access: Three lumens of central vascular access will be required for all patients entered on protocol due to the need for a dedicated line for continuous infusion cyclosporine.
* Informed Consent: The patient and/or the patient's legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained in accordance with the institutional policies approved by the U.S. Department of Health and Human Services.
* Patient organ function requirements:

  * Adequate renal function: Serum Creatinine \<\~1.5 x normal, or Creatinine clearance of 70 mL/min/1.73 mE2 or an equivalent GFR as determined by the institutional normal range
  * Adequate liver function: Total bilirubin \<1.5 x normal; and SGOT (AST) or SGPT (ALT) \<\~2.5 x normal
  * Adequate cardiac function: Shortening fraction of \>/=27% by echocardiogram
  * Adequate pulmonary function: FEV1/FVC \>/=60% by pulmonary function test; for children who are uncooperative, no evidence of dysnpea at rest, or exercise intolerance, and must have a pulse oximetry \>94% in room air
* Performance status: Lansky for children \</= 16 years \>/= 60; Karnofsky status for those \> 16 years of age \>/= 70
* Effective Contraceptive Use: Women of childbearing potential and sexually active males should use effective contraception while on study.

Exclusion Criteria:

* Patients who are pregnant or lactating
* Inability to find a suitable donor for the patient
* Patient is HIV-positive
* Patient has active Hepatitis B
* Disease progression or relapse prior to HPC infusion

**Maximum Age:** 21 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** mkletzel@northwestern.edu

**Name:** Morris Kletzel, MD

**Phone:** 773-880-4562

**Role:** CONTACT

**Contact 2:**

**Email:** TConterato@childrensmemorial.org

**Name:** Terriss Conterato

**Phone:** 773-880-8153

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Chicago

**Contacts:**

***Contact 1:***

- **Name:** Morris Kletzel, MD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** Children's Memorial Hospital

**State:** Illinois

**Status:** RECRUITING

**Zip:** 60614

#### Overall Officials

**Official 1:**

**Affiliation:** Ann & Robert H Lurie Children's Hospital of Chicago

**Name:** Morris Kletzel, MD

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000008206

- Term: Lymphatic Diseases

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000007945

- Term: Leukemia, Lymphoid

- ID: D000009196

- Term: Myeloproliferative Disorders

- ID: D000001855

- Term: Bone Marrow Diseases

- ID: D000002908

- Term: Chronic Disease

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10945

- Name: Leukemia

- Relevance: HIGH

- As Found: Leukemia

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M11220

- Name: Lymphoma

- Relevance: HIGH

- As Found: Lymphoma, Malignant

- ID: M9189

- Name: Graft vs Host Disease

- Relevance: LOW

- As Found: Unknown

- ID: M14164

- Name: Preleukemia

- Relevance: LOW

- As Found: Unknown

- ID: M12145

- Name: Myelodysplastic Syndromes

- Relevance: LOW

- As Found: Unknown

- ID: M27706

- Name: Leukemia, Myelomonocytic, Juvenile

- Relevance: LOW

- As Found: Unknown

- ID: M10951

- Name: Leukemia, Lymphoid

- Relevance: LOW

- As Found: Unknown

- ID: M27585

- Name: Precursor Cell Lymphoblastic Leukemia-Lymphoma

- Relevance: HIGH

- As Found: Leukemia, Lymphoblastic, Acute

- ID: M10955

- Name: Leukemia, Myeloid

- Relevance: HIGH

- As Found: Leukemia, Myelogenous

- ID: M18123

- Name: Leukemia, Myelogenous, Chronic, BCR-ABL Positive

- Relevance: HIGH

- As Found: Leukemia, Myelogenous, Chronic

- ID: M18127

- Name: Leukemia, Myeloid, Acute

- Relevance: HIGH

- As Found: Leukemia, Myelogenous, Acute

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M11203

- Name: Lymphatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12149

- Name: Myeloproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M5134

- Name: Bone Marrow Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6147

- Name: Chronic Disease

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

- ID: T3543

- Name: Lymphosarcoma

- Relevance: HIGH

- As Found: Lymphoma, Malignant

- ID: T2832

- Name: Homologous Wasting Disease

- Relevance: LOW

- As Found: Unknown

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

- ID: T3993

- Name: Myelodysplastic Syndromes

- Relevance: LOW

- As Found: Unknown

- ID: T1310

- Name: Chronic Myelomonocytic Leukemia

- Relevance: LOW

- As Found: Unknown

- ID: T3174

- Name: Juvenile Myelomonocytic Leukemia

- Relevance: LOW

- As Found: Unknown

- ID: T175

- Name: Acute Lymphoblastic Leukemia

- Relevance: HIGH

- As Found: Leukemia, Lymphoblastic, Acute

- ID: T3533

- Name: Lymphoblastic Lymphoma

- Relevance: HIGH

- As Found: Leukemia, Lymphoblastic, Acute

- ID: T1311

- Name: Chronic Myeloproliferative Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000008223

- Term: Lymphoma

- ID: D000007938

- Term: Leukemia

- ID: D000054198

- Term: Precursor Cell Lymphoblastic Leukemia-Lymphoma

- ID: D000007951

- Term: Leukemia, Myeloid

- ID: D000015464

- Term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive

- ID: D000015470

- Term: Leukemia, Myeloid, Acute

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: Derm

- Name: Dermatologic Agents

- Abbrev: Repr

- Name: Reproductive Control Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: AntiConv

- Name: Anticonvulsants

- Abbrev: AnEm

- Name: Antiemetics

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: PsychDr

- Name: Psychotropic Drugs

- Abbrev: Gast

- Name: Gastrointestinal Agents

### Intervention Browse Module - Browse Leaves

- ID: M11703

- Name: Methotrexate

- Relevance: LOW

- As Found: Unknown

- ID: M6727

- Name: Cyclophosphamide

- Relevance: LOW

- As Found: Unknown

- ID: M8191

- Name: Etoposide

- Relevance: LOW

- As Found: Unknown

- ID: M341643

- Name: Etoposide phosphate

- Relevance: LOW

- As Found: Unknown

- ID: M5336

- Name: Busulfan

- Relevance: LOW

- As Found: Unknown

- ID: M11140

- Name: Lorazepam

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
