Study of High-Dose Chemotherapy With Bone Marrow or Stem Cell Transplant for Rare Poor-Prognosis Cancers

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00141765
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Arm: 1
• Duration (Months): 157
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether very high dosages of chemotherapy will improve the chance of surviving cancer.

Condition or Disease	Intervention/Treatment	Phase
Wilms Tumor; Fibrosarcoma; Carcinoma, Round Cell; Nasopharyngeal Cancer; Brain Tumor, Recurrent	Procedure: Myeloablative Chemotherapy; Procedure: Stem Cell Rescue	Phase 2

Detailed Description

This is a phase II trial designed to provide a transplant option for patients with rare poor-prognosis cancers. The protocol is only open to patients with metastatic or relapsed cancers for whom the probability of remaining free of progressive disease for one year after being brought into remission is < 25%. Patients eligible for this study have been diagnosed with a form of cancer that leads to death more than 75% of the time when treated with standard therapy doses of chemotherapy and/ or radiation therapy. Under this treatment intensification protocol the expectation is that the one year progression-free survival for this group of patients will rise to 40%. Patients eligible for this protocol will be followed for one year post-transplant. Patients alive and free of progressive disease at the end of this period will be considered successes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Myeloablative Chemotherapy With Stem Cell Rescue for Rare Poor-Prognosis Cancers
• Study Start Date: Jan 1, 1997
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Myeloablative Chemotherapy with Stem Cell Rescue Myeloablative Chemotherapy, followed by stem cell rescue	Procedure: Myeloablative Chemotherapy; High dose chemotherapy (carboplatin and thiotepa) transplant rescue; Procedure: Stem Cell Rescue; autologous stem cell transplantation

Outcome Measures

Primary Outcome Measures

1. Percent of Participants With Progression Free Survival at 1 Year [1 year post transplant]

   The primary outcome measure for this study was to improve the long-term disease-free survival of patients with rare cancers at high risk for lethal relapse.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must be ineligible for other IRB-approved myeloablative regimens, be 21 years old or younger, and must have a histologically-confirmed Wilms' tumor, liver cancer, recurrent brain tumor of childhood, nasopharyngeal carcinoma, fibrosarcoma, desmoplastic small round cell tumor, germ cell tumor or other small round cell tumor, which:

1. is metastatic and has < 25% cure rate with conventional treatment; or

2. progressed after prior chemotherapy and has < 25% salvage rate with non-myeloablative therapies.

• Disease status: Within 3 weeks of initiation of this protocol, patients must:

1. be in a complete or good partial remission (section 7.4); or

2. have a "chemosensitive" tumor, which is defined as a > 50% decrease in at least one measurable tumor parameter attributable to prior chemotherapy, without evidence of progressive disease by any other parameter.

• Prior chemotherapy: Before entry to this protocol, patients must have derived maximal benefit from conventional, i.e., nonmyeloablative, doses of combination chemotherapy. Conventional therapy should be continued until either a complete remission is achieved, no further benefit from non-myeloablative dosing can be appreciated, or toxicity from conventional therapy is perceived as limiting in the absence of stem cell rescue. The cancer must be proven to be sensitive to alkylating agents. This means that, in addition to, or as part of, the appropriate chemotherapy protocol for the specific cancer in question, all patients must have received and responded to a minimum of:

1. 2 courses of high-dose cyclophosphamide, totaling > 4200 mg/m2; or

2. courses of high-dose ifosfamide totaling > 12 gm/m2.

3. 1 course of "a)" above, plus 1 course of 'b)" above.

4. Equivalent high dose alkylating agents as described in 3.3 a, b, and c.

• Patients must have adequate renal hepatic, and cardiac function (sections 4.4-4.6).

• Patients must meet at least one of the following stem cell requirements (Peripheral blood collection is to be preferred when available as an option):

1. Harvested bone marrow must contain 1 x 108 nucleated cells per kg of body weight, or,

2. Peripheral blood collection should include at least 2 x 106 CD34+ cells/kg.

• Informed consent must be signed indicating patient and/or parental awareness of the investigational nature of this program

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Michigan	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center

Investigators

• Principal Investigator: John E. Levine, MS MD, The Univeristy of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: John Levine, MD, Professor of Pediatrics and of Internal Medicine, University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT00141765
• Other Study ID Numbers: UMCC 9626; IRB 1996-195
• First Posted: Sep 1, 2005
• Last Update Posted: Jun 20, 2014
• Last Verified: May 1, 2014

• Additional relevant MeSH terms: Brain Neoplasms; Wilms Tumor; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Fibrosarcoma

Study Results

Participant Flow

Arm/Group Title	Myeloablative Chemotherapy With Stem Cell Rescue
Arm/Group Description	Myeloablative Chemotherapy: High dose chemotherapy (carboplatin and thiotepa) transplant rescue Stem Cell Rescue: autologous stem cell transplantation
Period Title: Overall Study
STARTED	25
COMPLETED	25
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Myeloablative Chemotherapy With Stem Cell Rescue
Arm/Group Description	Myeloablative Chemotherapy: High dose chemotherapy (carboplatin and thiotepa) transplant rescue Stem Cell Rescue: autologous stem cell transplantation
Overall Participants	25
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	6
Sex: Female, Male (Count of Participants)
Female	12 48%
Male	13 52%

Outcome Measures

1. Primary Outcome

Title	Percent of Participants With Progression Free Survival at 1 Year
Description	The primary outcome measure for this study was to improve the long-term disease-free survival of patients with rare cancers at high risk for lethal relapse.
Time Frame	1 year post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloablative Chemotherapy With Stem Cell Rescue
Arm/Group Description	Myeloablative Chemotherapy: High dose chemotherapy (carboplatin and thiotepa) transplant rescue Stem Cell Rescue: autologous stem cell transplantation
Measure Participants	25
Number [percentage of participants]	58 232%

Adverse Events

Arm/Group Title	Myeloablative Chemotherapy With Stem Cell Rescue
Arm/Group Description	Myeloablative Chemotherapy: High dose chemotherapy (carboplatin and thiotepa) transplant rescue Stem Cell Rescue: autologous stem cell transplantation
All Cause Mortality
	Myeloablative Chemotherapy With Stem Cell Rescue
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Myeloablative Chemotherapy With Stem Cell Rescue
	Affected / at Risk (%)	# Events
Total	19/25 (76%)
Blood and lymphatic system disorders
Neutropenic Fever	2/25 (8%)
Cardiac disorders
Hypertension	1/25 (4%)
Gastrointestinal disorders
Mucocitis	10/25 (40%)
Diarrhea	2/25 (8%)
Enterocolitis	1/25 (4%)
General disorders
Death	2/25 (8%)
Fever	6/25 (24%)
Graft Failure	1/25 (4%)
Immune system disorders
Febrile Transfusion Reaction	1/25 (4%)
Infections and infestations
Infection	11/25 (44%)
Investigations
Thrombocytopenia	1/25 (4%)
Metabolism and nutrition disorders
Hypokalemia	2/25 (8%)
Hypcalcemia	2/25 (8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease Relapse	1/25 (4%)
Renal and urinary disorders
Renal Failure	1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/25 (4%)
Tachypnea	2/25 (8%)
Hypoxia	1/25 (4%)
Skin and subcutaneous tissue disorders
Dermatitis	1/25 (4%)
Other (Not Including Serious) Adverse Events
	Myeloablative Chemotherapy With Stem Cell Rescue
	Affected / at Risk (%)	# Events
Total	12/25 (48%)
Ear and labyrinth disorders
Hearing Loss	2/25 (8%)
Gastrointestinal disorders
Esophagitis	2/25 (8%)
Mucocitis	2/25 (8%)
Investigations
ALK	3/25 (12%)
AST	6/25 (24%)
ALT	5/25 (20%)
Metabolism and nutrition disorders
Hypokalemia	8/25 (32%)
Hyperglycemia	4/25 (16%)
Hypocalcemia	5/25 (20%)
Hypomagnesemia	3/25 (12%)
Hypernatremia	2/25 (8%)
Hypercalcemia	2/25 (8%)
Hypoalbuminemia	4/25 (16%)
Hyperkalemia	3/25 (12%)
Hyponatremia	2/25 (8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.