High-Dose Melphalan, Total-Body Irradiation, and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma in First Relapse - Article Alkeran; L-PAM
Clinical Trial: High-Dose Melphalan, Total-Body Irradiation, and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma in First Relapse
This study is no longer recruiting patients.
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.
|Condition||Treatment or Intervention||Phase|
|stage II multiple myeloma |
stage III multiple myeloma
refractory plasma cell neoplasm
| Drug: cyclophosphamide |
|Phase II |
MedlinePlus related topics: Immune System and Disorders; Lymphatic Diseases; Multiple Myeloma
Study Type: Interventional
Study Design: Treatment
Study start: June 1993
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.
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.
PROTOCOL 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.
PROJECTED ACCRUAL: If 9 or fewer or 20 or more responses are seen in the first 50 patients treated, the study will be discontinued.
Ages Eligible for Study: 18 Years - 65 Years
PROTOCOL ENTRY CRITERIA:
- 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
- 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
- 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
Mayo Clinic Jacksonville, Jacksonville, Florida, 32224, United States
Mayo Clinic Cancer Center, Rochester, Minnesota, 55905, United States
Morie Abraham Gertz, Study Chair, Mayo Clinic Cancer Center
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.
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.
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.
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.
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.
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.
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.
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.
Record last reviewed: July 2004
Last Updated: October 13, 2004
Record first received: November 1, 1999
ClinicalTrials.gov Identifier: NCT00002630
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08
Cache Date: April 9, 2005