Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Projected Accrual
Outline
Trial Contact Information

Alternate Title

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Active Over 1 to 21 NCI COG-ADVL0316

Special Category: NIH Clinical Center trial

Objectives

Primary

1. Determine the maximum tolerated dose and recommended phase II dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) in pediatric patients with relapsed or refractory solid tumors or leukemia.
2. Determine the toxic effects of this drug in these patients.
3. Determine the pharmacokinetics of this drug in these patients.

Secondary

1. Determine, preliminarily, the antitumor activity of this drug in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed diagnosis of solid tumor or leukemia with documented M3 marrow
  • Histologic confirmation of intrinsic brain stem tumors not required



• Relapsed or refractory disease



• No known curative therapy



• In patients with CNS tumors, neurologic deficits must be stable for at least the past week

Prior/Concurrent Therapy:

Biologic therapy

• At least 7 days (or window for adverse effects has passed) since prior biologic therapy and recovered
• At least 7 days since prior hematopoietic growth factors
• At least 2 months since prior stem cell transplantation and no evidence of graft-vs-host disease
• No concurrent hematopoietic growth factors
• No concurrent biologic therapy
• No concurrent immunotherapy

Chemotherapy

• At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent steroid therapy

Radiotherapy

• At least 2 weeks since prior local palliative radiotherapy (small port)
• At least 3 months since prior total body irradiation or craniospinal radiotherapy
• At least 3 months since prior radiotherapy to ≥ 50% of the pelvis
• At least 6 weeks since prior substantial bone marrow radiotherapy
• Recovered from prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• No other concurrent investigational drugs
• No other concurrent anticancer agents
• No concurrent administration of medications known to be metabolized by the CYP4503A isoenzyme

Patient Characteristics:

Age

• 1 to 21

Performance status

• Karnofsky 50-100% (>10 years of age)
• Lansky 50-100% (≤ 10 years of age)

Life expectancy

• Not specified

Hematopoietic

• For patients with solid tumors:
  • Absolute neutrophil count ≥ 1,000/mm³
  • Platelet count ≥ 100,000/mm³ (transfusion independent)
  • Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
• For patients with leukemia:
  • Platelet count ≥ 20,000/mm³ (may receive platelet transfusions)
  • Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 2.5 times ULN
• Albumin ≥ 2 g/dL

Renal

• Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min

  OR

• Creatinine based on age as follows:
  • ≤ 0.8 mg/dL if ≤ 5 years of age
  • ≤ 1.0 mg/dL if > 5 years and ≤ 10 years of age
  • ≤ 1.2 mg/dL if > 10 years and ≤ 15 years of age
  • ≤ 1.5 mg/dL if > 15 years and ≤ 21 years of age

Other

• No uncontrolled infection
• No prior severe allergy to eggs
• No situation that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Projected Accrual

A maximum of 36 (3-24 with solid tumors and 12 with leukemia) will be accrued for this study.

Outline

This is a dose-escalation, multicenter study.

Patients with solid tumors receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 60 minutes on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Once the MTD is determined, up to 6 additional patients with leukemia receive 17-AAG at the MTD as above. If these 6 patients tolerate this regimen, another 6 leukemia patients receive 17-AAG IV over 60 minutes on days 1, 4, 8, 11, 15, and 18. Treatment repeats every 28 days for 17 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days.

Disclaimer

The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

The study sites listed for this clinical trial are potential study sites; however, not all sites may be participating.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Brenda Weigel, MD, Protocol chair		Ph: 612-626-6146; 888-226-2376
Joseph Neglia, MD, MPH, Protocol co-chair		Ph: 612-626-2778; 888-226-2376 Email: jneglia@umn.edu

U.S.A.
California
	Los Angeles
	Children's Hospital Los Angeles
		Paul Gaynon, MD	Ph:  323-669-2163
			Email: pgaynon@chla.usc.edu
	Palo Alto
	Lucile Packard Children's Hospital at Stanford University Medical Center
		Neyssa Marina, MD	Ph:  650-723-5535
			Email: neyssa.marina@stanford.edu
District of Columbia
	Washington
	Children's National Medical Center
		Nita Seibel, MD	Ph:  202-884-2144
			Email: nseibel@cnmc.org
Georgia
	Augusta
	MBCCOP-Medical College of Georgia Cancer Center
		Roger Vega, MD	Ph:  706-721-3626
Indiana
	Indianapolis
	Riley Children Cancer Center at Riley Hospital for Children
		Robert Fallon, MD, PhD	Ph:  317-274-8784
			Email: rfallon@iupui.edu
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
		NCI Clinical Studies Support	Ph:  888-NCI-1937
Massachusetts
	Boston
	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
		Holcombe Grier, MD	Ph:  617-632-3971
			Email: holcombe-grier@dfci.harvard.edu
Minnesota
	Minneapolis
	University of Minnesota Cancer Center
		Joseph Neglia, MD, MPH	Ph:  612-626-2778 888-226-2376
			Email: jneglia@umn.edu
	Rochester
	Mayo Clinic Cancer Center
		Carola Arndt, MD	Ph:  507-284-2511
			Email: carndt@mayo.edu
Mississippi
	Jackson
	University of Mississippi Medical Center
		Dale Jeanette Pullen, MD	Ph:  601-984-5220
New York
	Brooklyn
	SUNY Downstate Medical Center
		Sreedhar Rao, MD	Ph:  718-270-1693
	New York
	Herbert Irving Comprehensive Cancer Center at Columbia University
		Linda Granowetter, MD	Ph:  212-305-8652
			Email: lg519@columbia.edu
Ohio
	Cincinnati
	Cincinnati Children's Hospital Medical Center
		John Perentesis, MD	Ph:  513-636-6090 800-344-2462
Oregon
	Portland
	Doernbecher Children's Hospital at Oregon Health & Science University
		H. Nicholson, MD, MPH	Ph:  503-494-1543
Pennsylvania
	Philadelphia
	Children's Hospital of Philadelphia
		Beverly Lange, MD	Ph:  215-590-2249
			Email: Lange@email.CHOP.edu
	Pittsburgh
	Children's Hospital of Pittsburgh
		Arthur Kim Ritchey, MD	Ph:  412-692-5949
			Email: kim.ritchey@chp.edu
Tennessee
	Memphis
	St. Jude Children's Research Hospital
		Wayne Lee Furman, MD	Ph:  901-495-3300
Texas
	Dallas
	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
		Naomi Winick, MD	Ph:  214-648-3074
			Email: naomi.winick@utsouthwestern.edu
	Houston
	Texas Children's Cancer Center
		Susan Blaney, MD	Ph:  832-822-1482
			Email: sblaney@txccc.org
	San Antonio
	MBCCOP - South Texas Pediatrics
		Anne-Marie Langevin, MD	Ph:  210-704-3405
			Email: anne_langevin@srhc.lwsh.org
Washington
	Seattle
	Children's Hospital and Regional Medical Center - Seattle
		Douglas Hawkins, MD	Ph:  206-987-3096
Canada
Ontario
	Toronto
	Hospital for Sick Children
		Alberto Pappo, MD	Ph:  416-813-6594
			Email: alberto.pappo@sickkids.ca
Quebec
	Montreal
	Hopital Sainte Justine
		Albert Moghrabi, MD	Ph:  514-345-4969
			Email: albert.moghrabi@umontreal.ca

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