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High-Dose Melphalan, Total-Body Irradiation, and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma in First Relapse

Primary Purpose

Multiple Myeloma and Plasma Cell Neoplasm

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
filgrastim
cyclophosphamide
melphalan
peripheral blood stem cell transplantation
low-LET cobalt-60 gamma ray therapy
low-LET photon therapy
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma and Plasma Cell Neoplasm focused on measuring refractory multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Multiple myeloma confirmed by bone marrow plasmacytosis and with measurable M-component in the serum or urine by immunoelectrophoresis or immunofixation No Stage I myeloma No smoldering multiple myeloma Refractory to or in first relapse following an initial response to VAD (vincristine/doxorubicin/dexamethasone), with relapse defined as any of the following: 50% increase above the lowest remission level of serum or urine M-protein while on therapy 25-50% increase above the lowest remission level of serum or urine M-protein associated with either: Hypercalcemia (greater than 11 mg/dl) Hb decrease of 2 g/dl attributable to increasing marrow plasmacytosis Appearance of new lytic lesions Calcium no greater than 11 mg/dl No myeloma meningitis No plasma cell leukemia PATIENT CHARACTERISTICS: Age: 18 to 65 Performance status: ECOG 0-2 Hematopoietic: WBC greater than 500 (after G-CSF) Platelets greater than 25,000 Hepatic: Bilirubin no greater than 2.0 mg/dl Renal: Creatinine no greater than 2.0 mg/dl Cardiovascular: No NYHA class II-IV disease Pulmonary: DLCO at least 50% of predicted FVC at least 75% of predicted FEV1 at least 60% of predicted Other: No uncontrolled infection No active fungal infection No fever No prior malignancy within 5 years except: Basal cell skin cancer In situ carcinoma of the cervix No pregnant or nursing women PRIOR CONCURRENT THERAPY: Biologic therapy: Prior biological response modifiers allowed Chemotherapy: No time limit between cytotoxic therapy and protocol treatment Prior cumulative melphalan dose less than 300 mg Endocrine therapy: Corticosteroids for hypercalcemia allowed Radiotherapy: Prior radiotherapy allowed Prior pelvic radiotherapy allowed, but patients with such therapy are unlikely to have adequate PBSC harvested Surgery: Not specified

Sites / Locations

  • Mayo Clinic Jacksonville
  • Mayo Clinic Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
May 10, 2011
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00002630
Brief Title
High-Dose Melphalan, Total-Body Irradiation, and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma in First Relapse
Official Title
HIGH-DOSE MELPHALAN CHEMOTHERAPY AND TOTAL BODY RADIATION WITH PERIPHERAL BLOOD STEM-CELL RECONSTITUTION FOR PATIENTS WITH RELAPSING MULTIPLE MYELOMA
Study Type
Interventional

2. Study Status

Record Verification Date
May 2011
Overall Recruitment Status
Completed
Study Start Date
June 1993 (undefined)
Primary Completion Date
February 1999 (Actual)
Study Completion Date
May 2001 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining peripheral stem cell transplantation with chemotherapy and radiation therapy may allow the doctor to give higher doses of radiation and chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of high-dose melphalan plus total-body irradiation and peripheral stem cell transplantation in treating patients with multiple myeloma in first relapse.
Detailed Description
OBJECTIVES: I. Assess bone marrow reconstitution and peripheral blood cell counts of patients with multiple myeloma treated with high-dose melphalan (L-PAM) and total-body irradiation (TBI) followed by peripheral blood stem cell (PBSC) rescue. II. Assess the efficacy of intravenous L-PAM and TBI for treatment of relapsing/refractory myeloma. III. Assess the tolerability and toxicity of this regimen in patients with relapsing multiple myeloma. IV. Assess response rate and survival of relapsing/refractory patients treated with this regimen. OUTLINE: Prior to entry, patients will have received 3 monthly courses of standard VAD followed by PBSC collection on Regimen A; those who responded to VAD continue standard VAD to best response and upon relapse (on or off therapy) proceed to Regimen B. Patients with no response to 3 courses of VAD and those with no response to an alkylating-based regimen proceed immediately to Regimen B following PBSC collection. The following acronyms are used: CTX Cyclophosphamide, NSC-26271 G-CSF Granulocyte Colony Stimulating Factor (Amgen), NSC-614629 L-PAM Melphalan, NSC-8806 PBSC Peripheral Blood Stem Cells VAD Vincristine/Doxorubicin/Dexamethasone TBI Total Body Irradiation Regimen A: Stem Cell Mobilization/Harvest. CTX; G-CSF. Regimen B: Single-Agent Myeloablative Chemoradiotherapy with Stem Cell Rescue. L-PAM; TBI (Co60 or linear accelerators of 4 MV or greater); with PBSC. PROJECTED ACCRUAL: If 9 or fewer or 20 or more responses are seen in the first 50 patients treated, the study will be discontinued.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma and Plasma Cell Neoplasm
Keywords
refractory multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Type
Radiation
Intervention Name(s)
low-LET cobalt-60 gamma ray therapy
Intervention Type
Radiation
Intervention Name(s)
low-LET photon therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Multiple myeloma confirmed by bone marrow plasmacytosis and with measurable M-component in the serum or urine by immunoelectrophoresis or immunofixation No Stage I myeloma No smoldering multiple myeloma Refractory to or in first relapse following an initial response to VAD (vincristine/doxorubicin/dexamethasone), with relapse defined as any of the following: 50% increase above the lowest remission level of serum or urine M-protein while on therapy 25-50% increase above the lowest remission level of serum or urine M-protein associated with either: Hypercalcemia (greater than 11 mg/dl) Hb decrease of 2 g/dl attributable to increasing marrow plasmacytosis Appearance of new lytic lesions Calcium no greater than 11 mg/dl No myeloma meningitis No plasma cell leukemia PATIENT CHARACTERISTICS: Age: 18 to 65 Performance status: ECOG 0-2 Hematopoietic: WBC greater than 500 (after G-CSF) Platelets greater than 25,000 Hepatic: Bilirubin no greater than 2.0 mg/dl Renal: Creatinine no greater than 2.0 mg/dl Cardiovascular: No NYHA class II-IV disease Pulmonary: DLCO at least 50% of predicted FVC at least 75% of predicted FEV1 at least 60% of predicted Other: No uncontrolled infection No active fungal infection No fever No prior malignancy within 5 years except: Basal cell skin cancer In situ carcinoma of the cervix No pregnant or nursing women PRIOR CONCURRENT THERAPY: Biologic therapy: Prior biological response modifiers allowed Chemotherapy: No time limit between cytotoxic therapy and protocol treatment Prior cumulative melphalan dose less than 300 mg Endocrine therapy: Corticosteroids for hypercalcemia allowed Radiotherapy: Prior radiotherapy allowed Prior pelvic radiotherapy allowed, but patients with such therapy are unlikely to have adequate PBSC harvested Surgery: Not specified
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Morie A. Gertz, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Study Chair
Facility Information:
Facility Name
Mayo Clinic Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
11468153
Citation
Porrata LF, Gertz MA, Inwards DJ, Litzow MR, Lacy MQ, Tefferi A, Gastineau DA, Dispenzieri A, Ansell SM, Micallef IN, Geyer SM, Markovic SN. Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma. Blood. 2001 Aug 1;98(3):579-85. doi: 10.1182/blood.v98.3.579.
Results Reference
background
PubMed Identifier
11100277
Citation
Rajkumar SV, Fonseca R, Dispenzieri A, Lacy MQ, Witzig TE, Lust JA, Larson D, Therneau TM, Kyle RA, Litzow MR, Greipp PR, Gertz MA. Effect of complete response on outcome following autologous stem cell transplantation for myeloma. Bone Marrow Transplant. 2000 Nov;26(9):979-83. doi: 10.1038/sj.bmt.1702640.
Results Reference
background
PubMed Identifier
10918404
Citation
Gertz MA, Lacy MQ, Inwards DJ, Gastineau DA, Tefferi A, Chen MG, Witzig TE, Greipp PR, Litzow MR. Delayed stem cell transplantation for the management of relapsed or refractory multiple myeloma. Bone Marrow Transplant. 2000 Jul;26(1):45-50. doi: 10.1038/sj.bmt.1702445.
Results Reference
result
PubMed Identifier
10084252
Citation
Gertz MA, Lacy MQ, Inwards DJ, Chen MG, Pineda AA, Gastineau DA, Greipp PR, Lust JA, Tefferi A, Witzig TE, Kyle RA, Litzow MR. Early harvest and late transplantation as an effective therapeutic strategy in multiple myeloma. Bone Marrow Transplant. 1999 Feb;23(3):221-6. doi: 10.1038/sj.bmt.1701559.
Results Reference
result
PubMed Identifier
10482933
Citation
Rajkumar S, Fonseca R, Lacy M, Witzig T, Lust J, Greipp P, Therneau T, Kyle R, Litzow M, Gertz M. Abnormal cytogenetics predict poor survival after high-dose therapy and autologous blood cell transplantation in multiple myeloma. Bone Marrow Transplant. 1999 Sep;24(5):497-503. doi: 10.1038/sj.bmt.1701943.
Results Reference
result
PubMed Identifier
10459351
Citation
Rajkumar SV, Fonseca R, Dewald GW, Therneau TM, Lacy MQ, Kyle RA, Greipp PR, Gertz MA. Cytogenetic abnormalities correlate with the plasma cell labeling index and extent of bone marrow involvement in myeloma. Cancer Genet Cytogenet. 1999 Aug;113(1):73-7. doi: 10.1016/s0165-4608(99)00009-6.
Results Reference
result
PubMed Identifier
10414914
Citation
Rajkumar SV, Fonseca R, Lacy MQ, Witzig TE, Lust JA, Greipp PR, Therneau TM, Kyle RA, Litzow MR, Gertz MA. Autologous stem cell transplantation for relapsed and primary refractory myeloma. Bone Marrow Transplant. 1999 Jun;23(12):1267-72. doi: 10.1038/sj.bmt.1701805.
Results Reference
result
PubMed Identifier
10414913
Citation
Rajkumar SV, Fonseca R, Lacy MQ, Witzig TE, Lust JA, Greipp PR, Therneau TM, Kyle RA, Litzow MR, Gertz MA. Beta2-microglobulin and bone marrow plasma cell involvement predict complete responders among patients undergoing blood cell transplantation for myeloma. Bone Marrow Transplant. 1999 Jun;23(12):1261-6. doi: 10.1038/sj.bmt.1701787.
Results Reference
result

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High-Dose Melphalan, Total-Body Irradiation, and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma in First Relapse

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