## Protocol Section
### Identification Module
**NCT ID:** NCT00003079

**Brief Title:** Bryostatin 1 and High Dose Cytarabine in Treating Patients With Refractory or Relapsed Leukemia or Lymphoma

**Official Title:** Phase I Study of Bryostatin 1 (NSC 339555) and High-Dose 1-Beta-D-Arabinofuranosylcytosine (HiDAC) in Patients With Refractory Leukemia

#### Organization Study ID Info
**ID:** CDR0000065773
#### Organization
**Class:** OTHER
**Full Name:** Virginia Commonwealth University
#### Secondary ID Infos
**ID:** P30CA016059
**Link:** https://reporter.nih.gov/quickSearch/P30CA016059
**Type:** NIH
**ID:** MCV-MCC-9612-2E
**ID:** NCI-T97-0011
### Status Module
#### Completion Date
**Date:** 2001-05

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2010-02-17

**Type:** ESTIMATED

**Last Update Submit Date:** 2010-02-15

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2001-05

**Type:** ACTUAL

#### Start Date
**Date:** 1997-09

**Status Verified Date:** 2010-02

#### Study First Post Date
**Date:** 2004-05-27
**Type:** ESTIMATED
**Study First Submit Date:** 2000-05-02
**Study First Submit QC Date:** 2004-05-26
### Sponsor Collaborators Module

#### Collaborators

**Class:** NIH

**Name:** National Cancer Institute (NCI)

#### Lead Sponsor

**Class:** OTHER

**Name:** Virginia Commonwealth University

#### Responsible Party

**Old Name Title:** National Cancer Institute

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of bryostatin 1 and high dose cytarabine in treating patients with refractory or relapsed acute myelocytic or acute lymphocytic leukemia, chronic myelogenous leukemia or refractory or relapsed lymphoblastic lymphoma.

**Detailed Description:** OBJECTIVES: I. Define the maximum tolerated dose (MTD) of bryostatin 1 administered before and after high dose cytarabine in patients with refractory or relapsed acute myelocytic leukemia or acute lymphocytic leukemia, chronic myelogenous leukemia, or refractory or relapsed lymphoblastic lymphoma. II. Describe the toxic effects of bryostatin 1 and high dose cytarabine in these patients. III. Describe the time course of bryostatin 1 induced modulation of leukemic blast total protein kinase C (PKC) activity. IV. Describe bryostatin 1 pharmacokinetics. V. Correlate bryostatin 1 induced modulation of leukemic cell PKC activity or leukemic cell maturation with high dose cytarabine mediated apoptosis.

OUTLINE: This is a dose escalation study. Patients receive bryostatin 1 by continuous infusion over 24 hours on day 1. One hour after completion of bryostatin 1, patients receive high dose cytarabine IV over 3 hours every 12 hours on days 2-4. Patients again receive cytarabine over 3 hours every 12 hours on days 9-11, followed 1 hour later by bryostatin 1 by continuous infusion over 24 hours beginning on day 11. Patients achieving complete remission may receive up to 4 courses of consolidation chemotherapy. Consolidation chemotherapy is the same as induction chemotherapy except patients receive only 2 doses of cytarabine after day 1 completion of bryostatin and only 2 doses of cytarabine prior to the day 11 dose of bryostatin. Patients achieving partial remission may receive a second course of induction chemotherapy. In the absence of dose limiting toxicity in the first 3 patients treated, subsequent cohorts of 6 patients receive escalating doses of bryostatin 1 on the same schedule. If dose limiting toxicity occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and the current dose is defined as the maximum tolerated dose. Patients are followed every 6 months until death.

PROJECTED ACCRUAL: A total of 12-50 patients will be accrued for this study.

### Conditions Module

**Conditions:**

- Leukemia

- Lymphoma

**Keywords:**

- recurrent adult acute myeloid leukemia

- recurrent adult acute lymphoblastic leukemia

- blastic phase chronic myelogenous leukemia

- recurrent adult lymphoblastic lymphoma

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** FACTORIAL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 30

**Type:** ACTUAL

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

### Interventions

#### Intervention 1

**Name:** bryostatin 1

**Type:** DRUG

#### Intervention 2

**Name:** cytarabine

**Type:** DRUG

### Eligibility Module

**Eligibility Criteria:** DISEASE CHARACTERISTICS: Histologically confirmed primary refractory or relapsed acute myelocytic leukemia (AML) or acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML) in blast crisis, or refractory or relapsed lymphoblastic lymphoma Priority is given to patients previously treated with conventional high dose cytarabine regimen without bryostatin 1 Eligible if previously failed a conventional high dose cytarabine regimen or if underwent subsequent high dose therapy with bone marrow/stem cell transplantation with curative intent

PATIENT CHARACTERISTICS: Age: 18 and over (must be 60 or under if receiving higher dose of cytarabine) Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL (bilirubin no greater than 3.0 mg/dL and conjugated bilirubin no greater than 0.5 mg/dL if Gilbert's disease and predominantly unconjugated hyperbilirubinemia present) AST no greater than 2.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN Renal: Creatinine clearance at least 40 mL/min (at least 60 mL/min if receiving higher dose of cytarabine) Pulmonary: No clinically significant pulmonary disease Other: Not pregnant No patients who are poor medical risks because of nonmalignant systemic disease No serious, active, uncontrolled infection No prior or concurrent medical status that would make assessing cortical or cerebellar neurologic toxicity difficult

PRIOR CONCURRENT THERAPY: Recovery from the major toxic effects of prior therapy required Biologic therapy: See Disease Characteristics Chemotherapy: See Disease Characteristics At least 24 hours since prior chemotherapy with hydroxyurea At least 3 weeks since other prior systemic chemotherapy No prior clinically significant cerebellar toxicity due to cytarabine Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** New York

**Country:** United States

**Facility:** New York Presbyterian Hospital - Cornell Campus

**State:** New York

**Zip:** 10021

**Location 2:**

**City:** Houston

**Country:** United States

**Facility:** University of Texas - MD Anderson Cancer Center

**State:** Texas

**Zip:** 77030

**Location 3:**

**City:** Richmond

**Country:** United States

**Facility:** Massey Cancer Center

**State:** Virginia

**Zip:** 23298-0037

#### Overall Officials

**Official 1:**

**Affiliation:** Massey Cancer Center

**Name:** Steven Grant, MD

**Role:** STUDY_CHAIR

## 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

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10945

- Name: Leukemia

- Relevance: HIGH

- As Found: Leukemia

- ID: M10955

- Name: Leukemia, Myeloid

- Relevance: LOW

- As Found: Unknown

- ID: M18127

- Name: Leukemia, Myeloid, Acute

- Relevance: LOW

- As Found: Unknown

- ID: M10951

- Name: Leukemia, Lymphoid

- Relevance: LOW

- As Found: Unknown

- ID: M18123

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

- Relevance: LOW

- As Found: Unknown

- ID: M27585

- Name: Precursor Cell Lymphoblastic Leukemia-Lymphoma

- Relevance: LOW

- As Found: Unknown

- ID: M11220

- Name: Lymphoma

- Relevance: HIGH

- As Found: Lymphoma

- ID: M14850

- Name: Recurrence

- Relevance: LOW

- As Found: Unknown

- ID: M5033

- Name: Blast Crisis

- Relevance: LOW

- As Found: Unknown

- 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: T3995

- Name: Myeloid Leukemia

- Relevance: LOW

- As Found: Unknown

- ID: T182

- Name: Acute Myeloid Leukemia

- Relevance: LOW

- As Found: Unknown

- ID: T188

- Name: Acute Non Lymphoblastic Leukemia

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

- ID: T1309

- Name: Chronic Myeloid Leukemia

- Relevance: LOW

- As Found: Unknown

- ID: T175

- Name: Acute Lymphoblastic Leukemia

- Relevance: LOW

- As Found: Unknown

- ID: T3533

- Name: Lymphoblastic Lymphoma

- Relevance: LOW

- As Found: Unknown

- ID: T3543

- Name: Lymphosarcoma

- Relevance: LOW

- As Found: Unknown

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000008223

- Term: Lymphoma

- ID: D000007938

- Term: Leukemia

### Intervention Browse Module - Ancestors

- ID: D000000964

- Term: Antimetabolites, Antineoplastic

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000000998

- Term: Antiviral Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000276

- Term: Adjuvants, Immunologic

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M6766

- Name: Cytarabine

- Relevance: HIGH

- As Found: Infants

- ID: M211115

- Name: Bryostatin 1

- Relevance: HIGH

- As Found: Tretinoin

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M4314

- Name: Antiviral Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M3628

- Name: Adjuvants, Immunologic

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000003561

- Term: Cytarabine

- ID: C000046785

- Term: Bryostatin 1

### Misc Info Module

- Version Holder: 2024-05-24
